BMT CTN 2017 Progress Report

Progress April 2016 – Report March 2017

www.bmtctn.net

Center for International Blood and Marrow Transplant Research 9200 W. Wisconsin Avenue, Suite C5500, Milwaukee, WI 53226 USA Phone: (414) 805-0700 Fax: (414) 805-0714

The Emmes Corporation 401 N. Washington Street, Suite 700, Rockville, MD 20850 USA Phone: (301) 251-1161 Fax: (301) 251-1355

National Marrow Donor Program/Be The Match 500 N. 5th Street, Minneapolis, MN 55401 USA Phone: (763) 406-5800 Fax: (763) 406-4370

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 Table of Contents Table of Contents

1.0 Value the BMT CTN Brings to the HCT Community ...... 1 1.1 Areas of Study ...... 2 1.2 Accrual Success ...... 2 1.3 Dissemination of Results ...... 4 1.3.1 Publications ...... 4 1.3.2 Presentations ...... 5 1.4 Significant Findings and Impact ...... 5 1.5 Biorepository and Clinical Trial Data Resources ...... 18 1.6 Network Efficiency ...... 18 1.7 Funding Leverage ...... 19 1.8 Key Collaborations ...... 20 2.0 Organizational Overview ...... 21 2.1 Data and Coordinating Center ...... 21 2.2 Clinical Centers ...... 22 2.2.1 Core Centers ...... 22 2.2.2 Affiliate Centers ...... 25 2.3 Committee Structure ...... 27 2.3.1 Steering Committee ...... 27 2.3.2 Protocol Teams ...... 27 2.3.3 Technical Committees ...... 28 2.3.4 Administrative Committees ...... 29 2.3.5 Ad Hoc Committees ...... 30 2.3.6 Review Committees ...... 30 3.0 Administrative Functions of the DCC ...... 31 3.1 DCC Partner Organizations ...... 31 3.2 Policies and Procedures ...... 36 3.3 Administrative Support ...... 36 3.4 Fiscal Planning and Contracting Support ...... 36 3.4.1 Cost-Saving Mechanisms ...... 37 3.5 Communication ...... 37 3.5.1 Maintaining BMT CTN Websites ...... 37 3.5.2 Developing Patient Support and Marketing Materials ...... 38 3.5.3 Communicating Trial Results ...... 39 3.5.4 Social Media Engagement ...... 39 3.6 Training… ...... 40 3.7 Transplant Center Monitoring ...... 41 3.8 Specimen Repository Support ...... 43 3.8.1 Specimen Collection ...... 43

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 Table of Contents

3.8.2 Research Sample Repository and Central Processing Lab ...... 45 3.8.3 Maximizing Sample Collection, Quality, and Availability ...... 45 4.0 Concept to Publication: The Protocol Process...... 47 4.1 Concept Evaluation and Approval ...... 47 4.1.1 DCC Review ...... 47 4.1.2 Executive Committee Review ...... 48 4.1.3 Steering Committee Review ...... 48 4.2 Protocol Development ...... 48 4.2.1 Establishment of a Protocol Team ...... 48 4.2.2 Statistical Design ...... 48 4.2.3 Accrual Planning ...... 49 4.2.4 Budget Preparation ...... 50 4.2.5 Federal Regulations ...... 51 4.2.6 Final Draft Protocol ...... 51 4.3 Protocol Approval...... 51 4.3.1 Steering Committee Review ...... 51 4.3.2 Protocol Review Committee ...... 52 4.3.3 Data and Safety Monitoring Board Review ...... 52 4.3.4 Final Review Prior to Release to Centers ...... 53 4.4 Protocol Pre-Activation ...... 53 4.4.1 Designing Case Report Forms ...... 53 4.4.2 Educational Materials and Other Study Documents ...... 53 4.4.3 Release to Center IRBs ...... 54 4.4.4 Site Initiation Training ...... 54 4.4.5 Medical Monitor Assignment ...... 55 4.5 Protocol Activation ...... 55 4.6 Protocol Maintenance ...... 55 4.6.1 Accrual Monitoring and Intervention...... 55 4.6.2 Clinical and Laboratory Data Collection ...... 58 4.6.3 Data Audits ...... 59 4.6.4 Amendments ...... 60 4.7 Study Completion ...... 60 4.7.1 Notice to Cease Enrollment ...... 60 4.7.2 Follow-up Data Collection after Closure...... 60 4.7.3 Data Review and Analysis ...... 60 4.8 Dissemination of Results ...... 61 4.8.1 Authorship ...... 61 4.9 Ancillary and Correlative Studies ...... 61 5.0 Collaborations with other NIH-funded Research Networks ...... 74

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 Table of Contents

6.0 Future Directions ...... 75 6.1 Continued Planning for the Current Grant Cycle ...... 75 6.2 State of the Science Symposia ...... 75 6.2.1 2007 State of the Science Symposium ...... 75 6.2.2 2014 State of the Science Symposium ...... 78 6.3 Projected Study Activities during the Next Reporting Period ...... 82 6.3.1 Anticipated Results ...... 82 6.3.2 Studies Nearing Completion of Accrual ...... 82 6.3.3 Studies Activated ...... 83 6.3.4 Studies to be Activated ...... 84 6.3.5 Future Study Concepts ...... 84 6.4 Conclusions ...... 85 7.0 Protocol Descriptions...... 87 7.1 Protocols Open to Accrual ...... 87 BMT CTN 07LT ...... 88 BMT CTN 1101 ...... 90 BMT CTN 1102 ...... 92 BMT CTN 1201 / Alliance A051301 ...... 94 BMT CTN 1301 ...... 96 BMT CTN 1302 ...... 98 BMT CTN 1304 / DFCI 10-106 / IFM/DFCI 2009 (The DETERMINATION Study) ...... 100 BMT CTN 1401 ...... 102 BMT CTN 1501 ...... 105 BMT CTN 1503 ...... 107 BMT CTN 1505 ...... 109 7.2 Protocols that Completed Accrual during this Reporting Period ...... 111 BMT CTN 1202 ...... 112 BMT CTN 1203 ...... 114 BMT CTN 1205 ...... 116 7.3 Protocols that Completed Accrual during a Previous Reporting Period ...... 119 BMT CTN 0101 ...... 121 BMT CTN 0102 ...... 122 BMT CTN 0201 ...... 124 BMT CTN 0202 ...... 126 BMT CTN 0301 ...... 127 BMT CTN 0302 ...... 129 BMT CTN 0303 ...... 131 BMT CTN 0401 ...... 133 BMT CTN 0402 ...... 134 BMT CTN 0403 ...... 136 iii

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 Table of Contents

BMT CTN 0501 ...... 137 BMT CTN 0502 / CALGB 100103 ...... 138 BMT CTN 0601 ...... 139 BMT CTN 0603 / 0604 ...... 141 BMT CTN 0701 ...... 143 BMT CTN 0702 ...... 144 BMT CTN 0703 / SWOG 0410 ...... 145 BMT CTN 0704 / CALGB 100104 / ECOG 100104 ...... 146 BMT CTN 0801 ...... 148 BMT CTN 0802 ...... 149 BMT CTN 0803 ...... 151 BMT CTN 0804 / CALGB 100701 ...... 152 BMT CTN 0805 / SWOG 0805 ...... 153 BMT CTN 0901 ...... 154 BMT CTN 0902 ...... 155 BMT CTN 0903 ...... 157 BMT CTN 1204 ...... 158 7.4 Protocols Released to Centers ...... 161 BMT CTN 1502 ...... 162 BMT CTN 1506 ...... 164 Attachment A: Committee Rosters ...... 167 Attachment A1: Steering Committee Roster ...... 167 Attachment A2: Biomarkers Committee Roster ...... 169 Attachment A3: Clinical Research Associates Committee Roster ...... 170 Attachment A4: Pharmacy Committee Roster...... 171 Attachment A5: Special Populations (Pediatrics / Human Subjects) Committee Roster ...... 172 Attachment A6: Toxicity and Supportive Care Committee Roster...... 173 Attachment A7: Publications, Abstracts, and Presentations Committee Roster ...... 174 Attachment B: Publications, Abstracts, and Presentations ...... 175 Attachment B1: Publications by Year ...... 175 Attachment B2: Presentations by Year ...... 189 Attachment C: Center Performance Report ...... 203 Attachment C1: Center Performance Report Template ...... 203 Attachment C2: Center Performance Report Rating Metric ...... 210 Attachment D: Terms and Abbreviations ...... 212

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 1.0 Value the BMT CTN Brings to the HCT Community

1.0 Value the BMT CTN Brings to the HCT Community

The Blood and Marrow Transplant Clinical Trials Network (BMT CTN or the “Network”) was established in October 2001 to conduct large, multi-institutional clinical trials to improve the outcomes of hematopoietic cell transplantation (HCT) for patients facing life-threatening disorders. The BMT CTN allows the HCT community to conduct prospective, collaborative, clinical research within an infrastructure expressly designed to:  Facilitate effective communication and cooperation among transplant centers and collaborators at the National Institutes of Health (NIH), particularly the National Heart, Lung, and Blood Institute (NHLBI) and the National Cancer Institute (NCI);  Implement and complete well-designed, multicenter trials of high scientific merit;  Offer participation in HCT clinical trials to patients in all regions of the United States (US). About 22,000 HCTs are performed in the US annually, and the number increases by approximately 2% per year. This increase reflects the utility of HCT in treating both malignant and non-malignant diseases, higher donor availability, and treatment advances that allow HCT to be performed in older and sicker patients. While HCT is a rapidly evolving field, HCT clinical trials face unique challenges, including the relatively small number of transplantations performed at any single center, the diverse indications for HCT, the complexities of the procedure, and multiple competing risks in the post-transplant period. The BMT CTN was established to address these challenges and execute multicenter HCT trials with broad national participation. The Network:  Effectively fosters development of innovative and important concepts into well-designed trials that answer questions in the most efficient manner;  Supports timely implementation and completion of those trials;  Ensures protection of subjects (both donors and recipients);  Provides high-quality data and adherence to regulatory requirements in an increasingly complex environment;  Promotes timely publication of study results, which advances the field of HCT and impacts patient care. The BMT CTN and its network of Core and Affiliate Centers (Section 2.2) play a critical role in improving patient outcomes and advancing the science of HCT. The BMT CTN’s many scientific achievements include:  Launching 44 trials, including 6 this reporting period;  Completing accrual to 31 trials, including 3 this reporting period;  Accruing almost 9,500 patients to its trials from more than 100 centers, including more than 600 patients this reporting period;  Achieving an overall accrual rate that is 106% of projections among trials that are currently open for enrollment;  Establishing a Research Sample Repository that currently includes more than 390,000 biospecimens;  Engaging in 30 ancillary and correlative studies; 23 of these studies used cryopreserved biospecimens from the BMT CTN Research Sample Repository or samples shipped directly to a project laboratory, and 9 were completed and published this reporting period;  Publishing 73 manuscripts, including 15 this reporting period;  Presenting 80 abstracts, including 15 this reporting period.

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 1.0 Value the BMT CTN Brings to the HCT Community

This Progress Report highlights the following: 1. Accomplishments of the BMT CTN, including a detailed report of the Network’s progress for the period of April 1, 2016, through March 31, 2017, (highlights bolded throughout the report) as well as plans for the upcoming year; 2. Organizational structure of the Network; 3. Structure, responsibilities, and focus of the Network’s Data and Coordinating Center (DCC); 4. Network collaborations; 5. Protocol selection, development, and management processes; 6. Past, current, and future protocol status updates. 1.1 Areas of Study The BMT CTN studies diverse transplant and cellular therapy treatment options, including both allogeneic and autologous transplantation, with a focus on more complex allografting issues. During this reporting period, 98% of the transplants performed on BMT CTN studies were allogeneic. Comparatively, 42% of the transplants reported to the Center for International Blood and Marrow Transplant Research® (CIBMTR®) in 2016 were allogeneic transplants. The BMT CTN has answered relevant research questions in both common and rare diseases. Its research portfolio includes studies in leukemia, myelodysplasia, lymphoma, and multiple myeloma as well as rare transplant indications, such as aplastic anemia, sickle cell disease, human immunodeficiency virus (HIV)- associated cancers, and hemophagocytic syndromes / primary immune deficiencies. Issues addressed and being addressed include:  Comparison of HCT to non-transplant standard therapies for myelodysplastic syndromes (MDS) and sickle cell disease;  Optimal timing of HCT;  Pre-transplant conditioning regimens;  Graft source [autologous, human leukocyte antigen (HLA)-identical and haploidentical related donors, unrelated donors, and umbilical cord blood];  Anticancer vaccine therapy;  Acute and chronic graft-versus-host disease (GVHD);  Graft manipulation to decrease GVHD;  Maintenance therapy;  Post-transplant infection;  Post-transplant organ toxicity;  Disease control;  Biomarkers for transplant complications;  Outcomes of transplant in patient populations of all ages, including children and older adults;  Quality of life;  Better ways of obtaining consent. 1.2 Accrual Success During this reporting period, BMT CTN trials accrued more than 600 patients, bringing the Network total to almost 9,500. Among the eight Network-led protocols currently open, the overall accrual rate is 106% of target projections. Figure 1.1 displays a graph of BMT CTN total annual accrual by progress report time frame (April 1 – March 31).

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 1.0 Value the BMT CTN Brings to the HCT Community

Figure 1.1. BMT CTN annual and cumulative accrual

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 1.0 Value the BMT CTN Brings to the HCT Community

To fully leverage accrual efforts, several BMT CTN studies are designed for co-enrollment, including studies on quality of life (0902), consent form evaluation (1205), and a biomarker repository protocol (1202). Approximately 540 patients co-enrolled on more than one Network study. The BMT CTN also leverages the outcomes registry of the CIBMTR, which is funded by the NHLBI, NCI, National Institute of Allergy and Infectious Diseases (NIAID), and Health Services and Research Administration. This registry captures data on almost all transplants performed in the US, and the Network utilizes it to design studies to maximize accrual, recruit centers likely to accrue to specific protocols, and monitor accrual so that issues can be addressed early in the course of protocols. Accrual to BMT CTN studies closely mirrors the CIBMTR database in gender and racial composition. Males are over-represented because several of the common indications for transplantation (e.g. multiple myeloma, acute lymphoblastic leukemia, etc.) are either more common in males or have a worse prognosis with standard chemotherapy in males, leading to increased use of transplantation. 1.3 Dissemination of Results 1.3.1 Publications BMT CTN investigators have published 73 manuscripts, including 21 primary study results papers, from 24 trials and the DCC / Network in the peer-reviewed journals listed below. Fifteen manuscripts were published during this reporting period in the journals listed in bold below. Five of these manuscripts were primary results papers. An additional five manuscripts were submitted for publication, including a primary results manuscript.  American Journal of Health-System Pharmacy;  Biology of Blood and Marrow Transplantation;  Blood;  Blood Advances;  British Journal of Haematology;  Cancer;  Clinical Infectious Diseases;  Clinical Trials;  Current Malignancy Hematology Reports;  JAMA (Journal of the American Medical Association) Oncology;  Journal of Antimicrobial Chemotherapy;  Journal of Clinical Oncology;  Journal of Comparative Effectiveness Research;  Journal of Immunology;  Journal of the National Cancer Institute;  Journal of the Society for Clinical Trials;  Lancet Haematology;  Lancet Oncology;  Molecular Therapy;  New England Journal of Medicine;  Statistics in Medicine. All trials with primary results available for publication were published or submitted except 0702, 0801, and 0903, for which data only became available during the current reporting period. Manuscripts for all three studies will be submitted during the next reporting period. A full list of the Network’s publications is provided in Appendix B1.

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 1.0 Value the BMT CTN Brings to the HCT Community 1.3.2 Presentations BMT CTN investigators have presented 80 abstracts from 26 trials and the DCC / Network at the national and international meetings listed below. Fifteen abstracts were presented during this reporting period at the meetings listed in bold below. A full list of the Network’s presentations is provided in Appendix B2.  American Society of Clinical Oncology (ASCO);  American Society of Hematology (ASH), including the 2011 Plenary Session;  BMT Tandem Meetings;  European Group for Blood and Marrow Transplantation (EBMT);  European Hematology Association;  International Myeloma Workshop;  International Society for Cellular Therapy;  Interscience Conference on Antimicrobial Agents and Chemotherapy;  Institute for Healthcare Advancement’s Annual Health Literacy Conference;  IPOS/APOS World Congress on Psycho-Oncology;  NCI-ASCO Cancer Trial Accrual Symposium;  PsychoNeuroImmunology Research Society;  Public Responsibility in Medicine and Research;  Society for Clinical Trials. 1.4 Significant Findings and Impact The research findings of the BMT CTN provide information with effects on clinical practice. To date, BMT CTN trials have provided important insights into several areas of HCT (Table 1.1). Full citations for the publications listed in the table, as well as all others from the BMT CTN, are provided in Appendix B1.

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 1.0 Value the BMT CTN Brings to the HCT Community

Table 1.1. Significant findings and impact of BMT CTN studies Significant Findings and Impact of BMT CTN Studies BMT CTN Study Results Relevant Publications Impact / Future Outlook

CONDITIONING REGIMENS / INTENSITY

0401: Phase III Determined the Phase III randomized study of Although several small Phase II Rituxan / BEAM addition of rituximab/carmustine, studies suggested that dose- versus Bexxar / radioimmunotherapy etoposide, cytarabine, and intensification might decrease BEAM with to the standard melphalan (BEAM) compared relapse, the primary cause of autologous conditioning regimen with Iodine-131 tositumomab / treatment failure after autologous hematopoietic stem of BEAM provides no BEAM with autologous HCT for DLBCL, this study failed to cell transplantation clinical benefit for hematopoietic cell show an impact on relapse but did for persistent or patients undergoing transplantation for relapsed show increased toxicity. Future trials relapsed autologous HCT for diffuse large B-cell lymphoma: will focus on maintenance strategies chemotherapy DLBCL results from the BMT CTN 0401 and/or immune therapies after HCT to sensitive diffuse Trial. Journal of Clinical improve disease control, marking a large B cell non- Oncology. 2013 May 1; 31(13): significant change in direction for the Hodgkin’s 1662-1668. Epub 2013 Mar 11. field. lymphoma (DLBCL) BMT CTN collaborated with Alliance to design a randomized double blind Phase III study of ibrutinib during and following autologous HCT vs. placebo in patients with relapsed or refractory DLBCL (Alliance A051301 / BMT CTN 1201). This protocol was activated during this reporting period.

0502: A Phase II Demonstrated the Phase II study of allogeneic This protocol was a collaborative study of allogeneic feasibility and transplantation for older patients effort between the BMT CTN and transplant for older effectiveness of with AML in first complete Cancer and Leukemia Group B patients with acute allogeneic transplant remission using a reduced- (CALGB). CALGB accrual began in myeloid leukemia using reduced- intensity conditioning regimen: 2006, but enrollment was low; BMT (AML) in first intensity conditioning Results from Cancer and CTN activated the study, and the trial morphologic in this first Leukemia Group B 100103 rapidly met its original accrual goal. complete remission prospective US (Alliance for Clinical Trials in The study demonstrates that, with using a cooperative group Oncology) / Blood and Marrow reduced-intensity conditioning, nonmyeloablative trial conducted in a Transplant Clinical Trial Network patients older than 60 can benefit preparative homogeneously 0502. Journal of Clinical from the graft-versus-leukemia regimen treated group of older Oncology. 2015 Dec 10; 33(35): effects of allogeneic HCT with AML patients in first 4167-4175. Epub 2015 Nov 2. outcomes similar to younger patients. remission These data should increase the use of HCT in older AML patients and provide justification for BMT CTN allograft trials.

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 1.0 Value the BMT CTN Brings to the HCT Community

Significant Findings and Impact of BMT CTN Studies BMT CTN Study Results Relevant Publications Impact / Future Outlook

CONDITIONING REGIMENS / INTENSITY (continued)

0701: Phase II trial Determined that a Reduced-intensity conditioning This study demonstrated that of non- rituximab-containing with fludarabine, allogeneic HCT using a rituximab- myeloablative reduced-intensity cyclophosphamide, and high- containing reduced-intensity allogeneic conditioning regimen dose rituximab for allogeneic conditioning regimen confers high hematopoietic cell is safe and efficacious HCT for follicular lymphoma: A complete response rates, a low transplantation for for patients with Phase Two multicenter trial from incidence of relapse / progression, and patients with relapsed follicular non- the BMT CTN. Biology of Blood prolonged survival with acceptable relapsed follicular Hodgkin lymphoma Marrow Transplantation. 2016 toxicity in heavily pretreated follicular non-Hodgkin’s Aug 1; 22(8):1440-1448. Epub lymphoma patients. This study lymphoma beyond 2016 Apr 23. provides justification for future trials first complete comparing nontransplant with response transplant salvage strategies in this disease.

0901: A Found that reduced- Myeloablative vs. reduced- The data from this trial support randomized, multi- intensity conditioning intensity HCT for AML and MDS. myeloablative conditioning as the center Phase III results in higher Journal of Clinical Oncology. standard of care for patients who are study of allogeneic relapse rates and 2017 Apr 10; 35(11):1154-1161. able to receive it. For patients who stem cell lower treatment- Epub 2017 Feb 13. are not candidates for myeloablative transplantation related mortality conditioning, novel regimens, which comparing regimen compared to incorporate enhanced anti-leukemia intensity in patients myeloablative activity without increasing toxicity, are with conditioning needed. One such regimen of myelodysplastic maintenance therapy post-HCT for syndrome or acute FLT3-positive AML patients will be myeloid leukemia evaluated in an upcoming study (BMT CTN 1506).

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 1.0 Value the BMT CTN Brings to the HCT Community

Significant Findings and Impact of BMT CTN Studies BMT CTN Study Results Relevant Publications Impact / Future Outlook GRAFT SOURCES

0201: A Phase III Found no difference in Peripheral-blood stem cells Peripheral blood has largely replaced randomized, survival for recipients versus bone marrow from bone marrow as a graft source for multicenter trial of unrelated donor unrelated donors. New England unrelated donor transplantation. This comparing G-CSF peripheral blood Journal of Medicine. 2012 Oct study suggests this may not be mobilized versus bone marrow 18; 367(16): 1487-1496. appropriate in the myeloablative peripheral blood grafts, but an conditioning setting since it offers no Comparison of characteristics stem cell with increased risk of survival advantage but produces and outcomes of trial marrow chronic GVHD higher rates of chronic GVHD requiring participants and nonparticipants: transplantation requiring prolonged prolonged immune suppression. Example of Blood and Marrow from HLA immune suppression Transplant Clinical Trials Network Five year results of patient-reported compatible with peripheral blood 0201 Trial. Biology of Blood and outcomes showed a quality of life unrelated donors grafts Marrow Transplantation. 2015 advantage for recipients of bone Five-year quality of life Oct 1; 21(10): 1815-1822. Epub marrow grafts although the impact on follow-up results 2015 Jun 11. unrelated donor requests is yet to be showed that recipients determined. Infections after transplantation of bone marrow grafts of bone marrow or PBSC from Ancillary studies of immune have better unrelated donors. Biology of reconstitution, infection, and donor psychological well- Blood and Marrow clinical outcomes and quality of life being and less Transplantation. 2016 Feb 1; were published. An analysis burdensome chronic 22(2): 359-370. Epub 2015 Sep performed in collaboration with the GVHD symptoms than 25. CIBMTR demonstrated that the recipients of patients and outcomes in this study peripheral blood grafts Recovery of unrelated donors of were representative of the larger BMT PBSC versus bone marrow: A population was also published. prespecified analysis from the Phase III BMT CTN Protocol 0201. This is the largest study of unrelated Biology of Blood and Marrow donor transplantation ever Transplantation. 2016 Jun 1; performed and would not have been 22(6): 1108-1116. Epub 2016 possible without the infrastructure Mar 21. provided by the BMT CTN. Comparison of patient-reported outcomes in 5-Year Survivors who received bone marrow vs peripheral blood unrelated donor transplantation: Long- term follow-up of a randomized clinical trial. JAMA Oncology. 2016 Dec 1; 2(12): 1583-1589. Epub 2016 Aug 11.

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 1.0 Value the BMT CTN Brings to the HCT Community

Significant Findings and Impact of BMT CTN Studies BMT CTN Study Results Relevant Publications Impact / Future Outlook

GRAFT SOURCES (continued)

0501: Multi-center, Demonstrated no One- versus two-unit cord blood This study indicates, unexpectedly, open label, survival benefit and transplant for leukemia. New that increasing cell dose beyond the randomized trial more acute GVHD for England Journal of Medicine. accepted minimum by adding comparing single children receiving 2014 Oct 30; 371(18): 1685- another cord blood unit does not versus double infusion of two 1694. improve survival after cord blood umbilical cord umbilical cord blood transplantation in children and blood units versus one increases the risk of acute GVHD. This transplantation in umbilical cord blood has important implications for future pediatric patients unit after strategies to improve hematopoietic with leukemia and transplantation for recovery and decrease transplant- myelodysplasia hematologic related mortality after cord blood malignancies HCT.

0603 / 0604: Confirmed single- Alternative donor Acceptable outcomes of double cord Multicenter, Phase center results in a transplantation: results of and haploidentical bone marrow II trials of non- multicenter setting parallel Phase II trials using HLA- transplantation suggest that many myeloablative using reduced- mismatched related bone more adults should be offered HCT, conditioning and intensity conditioning marrow or unrelated umbilical even when an HLA-matched adult transplantation of and haploidentical cord blood grafts. Blood. 2011 Jul donor is not available. Publication of partially HLA- bone marrow 14; 118(2): 282-288. Epub 2011 these studies led to substantial mismatched bone transplantation or Apr 28. increase in use of haploidentical marrow / umbilical double cord blood donors for transplantation in the US. Mismatched related and cord blood from transplantation in These approaches are now being unrelated donors for allogeneic unrelated donors in adults with compared in a randomized Phase III hematopoietic cell patients with hematologic trial (BMT CTN 1101). transplantation for adults with hematologic malignancies, with hematologic malignancies. A subsequent three-year follow-up malignancies data supporting a Biology of Blood and Marrow analysis was conducted and showed subsequent Phase III Transplantation. 2014 Oct 1; continued evidence of equipoise trial 20(10):1485-1492. Epub 2014 between HLA haploidentical related May 23. donor and double umbilical cord blood transplantation. Comparable outcomes with marrow or peripheral blood as stem cell sources for HCT from haploidentical donors after non- ablative conditioning: A matched-pair analysis. Bone Marrow Transplantation. 2016 Dec 1; 51(12):1599-1601. Epub 2016 Aug 15.

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 1.0 Value the BMT CTN Brings to the HCT Community

Significant Findings and Impact of BMT CTN Studies BMT CTN Study Results Relevant Publications Impact / Future Outlook GVHD PREVENTION AND TREATMENT

0302: Initial Identified Etanercept, mycophenolate, The results from the 0302 study were systemic treatment mycophenolate denileukin or pentostatin plus used to create and conduct BMT CTN of acute GVHD: A mofetil (MMF) plus corticosteroids for acute GHVD, a 0802, a Phase III randomized study of Phase II randomized corticosteroids as the randomized Phase II trial from MMF / corticosteroids vs. trial evaluating most promising the BMT CTN. Blood. 2009 Jul 1; corticosteroids alone. etanercept, regimen to compare 114(3): 511-517. Epub 2009 May The wider use of biomarkers to mycophenolate against corticosteroids 14. identify patients at high risk of GVHD mofetil, denileukin alone in a Phase III trial Graft-versus-host disease will allow us to tailor our therapies to diftitox (Ontak), and Determined that treatment: predictors of survival. better control this complication in pentostatin in GVHD biomarker Biology of Blood and Marrow these patients and to reduce toxicity combination with panels can be used for Transplantation. 2010 Dec; in patients who are unlikely to benefit corticosteroids early identification of 16(12): 1693-1699. Epub 2010 from intensive immune suppression. patients at high or low Jun 10. The BMT CTN is now incorporating risk for treatment biomarker-defined risk stratification Acute GVHD biomarkers non-responsiveness or into the design of GVHD treatment measured during therapy can death and that trials, currently with the BMT CTN predict treatment outcomes: A biomarker panels may 1501 protocol (treatment of low risk BMT CTN study. Blood. 2012 Apr provide opportunities GVHD as identified by biomarkers), 19; 119(16): 3854-3860. Epub for early intervention which was released this reporting 2012 Mar 1. and improved survival period. following HCT A prognostic score for acute GVHD based on biomarkers: A multicentre study. Lancet Haematology.2015 Jan 1; 2(1): 21-29. Epub 2014 Dec 22. A refined risk score for acute GVHD that predicts response to initial therapy, survival, and transplant-related mortality. Biology of Blood and Marrow Transplantation. 2015 Apr 1; 21(4): 761-767. Epub 2015 Jan 10. Additional secondary analyses published in previous reporting periods are listed in the BMT CTN 0302 Protocol Table in Section 7.3.

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 1.0 Value the BMT CTN Brings to the HCT Community

Significant Findings and Impact of BMT CTN Studies BMT CTN Study Results Relevant Publications Impact / Future Outlook

GVHD PREVENTION AND TREATMENT (continued)

0303: A single-arm, Confirmed in a Low risk of chronic GVHD and These data were used by the US Food multicenter Phase II multicenter setting relapse associated with T cell and Drug Administration (FDA) in its trial of transplants the feasibility and depleted PBSC transplantation determination to approve the of HLA-matched, consistency of T cell for AML in first remission: results Miltenyi CD34 selection column for CD34+ enriched, T depletion by CD34 of the BMT CTN Protocol 0303. clinical use. It is the only CD34 cell depleted selection, with results Biology of Blood and Marrow selection device available in the US. A peripheral blood in AML that warranted Transplantation. 2011 Sep; 17(9): comparative analysis of outcomes for stem cells isolated consideration of a 1343-1351. Epub 2011 Feb 12. patients enrolled on this study and by the CliniMACS Phase III trial versus patients enrolled on another BMT CTN Characteristics of CliniMACS(®) system in the non-T cell depleted study who received T-replete grafts System CD34-enriched T cell- treatment of transplantation was also undertaken. The results depleted grafts in a multicenter patients with AML suggested that T cell depletion via trial for AML - BMT CTN Protocol in first or second CD34 selection may lower long term 0303. Biology of Blood and morphologic morbidity as a result of less chronic Marrow Transplantation. 2012 complete remission GVHD. A Phase III three arm trial May; 18(5): 690-697. Epub 2011 comparing outcomes of CD34-selected Aug 26. transplants using this approach vs. Comparative outcomes of donor another calcineurin inhibitor-free graft CD34+ selection and strategy (post-transplant immune suppressive therapy as cyclophosphamide) vs. standard GVHD prophylaxis for patients calcineurin-inhibitor based GVHD with AML in complete remission prophylaxis (tacrolimus / undergoing HLA-matched sibling methotrexate) is currently enrolling allogeneic HCT. Journal of Clinical patients (BMT CTN 1301). Oncology. 2012 Sep 10; 30(26): 3194-3201. Epub 2012 Aug 6.

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 1.0 Value the BMT CTN Brings to the HCT Community

Significant Findings and Impact of BMT CTN Studies BMT CTN Study Results Relevant Publications Impact / Future Outlook

GVHD PREVENTION AND TREATMENT (continued)

0402: A Phase III Identified a high risk of Sirolimus is associated with Although the study showed a modest randomized, toxicity when sirolimus veno-occlusive disease of the improvement in grade III-IV acute multicenter trial is substituted for liver after myeloablative GVHD, the findings do not support comparing sirolimus standard allogeneic stem cell substituting sirolimus for / tacrolimus with methotrexate for transplantation. Blood. 2008 Dec methotrexate since it may increase tacrolimus / GVHD prophylaxis 1; 112(12)4425-4431. Epub 2008 toxicity in patients who receive methotrexate as when the conditioning Sep 5. busulfan for conditioning, it was GVHD prophylaxis regimen includes associated with higher risks of chronic Tacrolimus / sirolimus versus after HLA-matched, busulfan and no GVHD, and it did not improve survival. tacrolimus / methotrexate as related peripheral advantage in acute Novel approaches to preventing GVHD prophylaxis after matched, blood stem cell GVHD-free survival GVHD are needed and are being related donor allogeneic transplantation explored in the BMT CTN 1203 hematopoietic cell PROGRESS I study, which completed transplantation. Blood. 2014 Aug accrual this reporting period, and the 21; 124(8): 1372-1377. Epub BMT CTN 1301 PROGRESS II study, 2014 Jun 30. which is currently enrolling patients. Plasma biomarkers of risk for An ancillary study using plasma death in a multicenter Phase 3 samples from patients enrolled in trial with uniform transplant BMT CTN 0402 was conducted this characteristics post-allogeneic reporting period and confirmed the HCT. Blood. 2017 Jan 12; 129(2): correlation of plasma-derived proteins 162-170. Epub 2016 Nov 8. with clinical outcomes after allogeneic HCT, an association previously assessed in single-center cohorts.

0802: A multi- Found no GVHD-free Phase III clinical trial steroids / Although the 0802 results were center, randomized, survival benefit with mycophenolate mofetil vs discouraging, the BMT CTN has used double blind, Phase the addition of MMF steroids / placebo as therapy for these studies to focus on a newer III trial evaluating acute GVHD: BMT CTN 0802. therapeutic agent, sirolimus, in the See page 10 for 0302 / corticosteroids with Blood. 2014 Nov 20; 124(22): current BMT CTN 1501 study using a 0802 ancillary study mycophenolate 3221-3227. Epub 2014 Aug 26. biomarker risk stratification results mofetil versus developed in BMT CTN 0302 and corticosteroids with 0802. The Network’s ability to conduct placebo as initial GVHD studies in timely manner allows systemic treatment for definitive Phase III results to be of acute GVHD quickly disseminated and promising agents to be efficiently tested in new studies.

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 1.0 Value the BMT CTN Brings to the HCT Community

Significant Findings and Impact of BMT CTN Studies BMT CTN Study Results Relevant Publications Impact / Future Outlook MULTIPLE MYELOMA TREATMENT

0102: A trial of Determined, in the Autologous haemopoietic stem- This study highlights the need to tandem autologous second largest study cell transplantation followed by reduce transplant-related toxicity in stem cell of HCT for multiple allogeneic or autologous the allogeneic HCT setting to allow the transplants with or myeloma ever haemopoietic stem-cell graft-versus-tumor effect of allografts without post- conducted transplantation in patients with to translate into survival benefits. It second autologous (superseded only by multiple myeloma (BMT CTN also indicated that the graft-versus- transplant BMT CTN 0702), that 0102): A Phase 3 biological tumor effect in standard risk myeloma maintenance tandem autologous assignment trial. Lancet may not be as important as previously therapy versus HCT and autologous Oncology. 2011 Dec 1; 12(13): thought. The use of tandem single autologous HCT followed by 1195-1203. Epub 2011 Sep 29. autologous-allogeneic HCTs has stem cell transplant allogeneic HCT offer decreased substantially over the past Heavy / light chain ratio followed by similar progression- few years, in part, because of the normalization prior to transplant matched sibling free survival rates in data from this trial. Evaluation of the is of independent prognostic nonmyeloablative patients with standard high-risk cohort informed the significance in multiple myeloma: allogeneic stem cell risk disease Network's next allogeneic transplant A BMT CTN 0102 correlative transplant for trial in this disease (BMT CTN 1302), study. British Journal of patients with which is enrolling patients. Haematology. 2016 Jun 13. multiple myeloma [Epub ahead of print]. An ancillary study was conducted this reporting period indicating the heavy light chain immunoassay independently prognosticated patients with multiple myeloma beyond electrophoretic response.

0704: A Phase III, Determined Phase III study of lenalidomide The data have led to a major change randomized, lenalidomide versus placebo after HCT for in clinical practice, with most double-blind study maintenance therapy multiple myeloma. New England myeloma patients now receiving of maintenance dramatically improves Journal of Medicine. 2012 May lenalidomide maintenance after therapy with progression-free 10; 366(19): 1770-1781. transplantation. CC-5013 or placebo survival and overall Anatomy of a successful practice- The BMT CTN was an important following survival after changing study: A BMT CTN – NCI contributor to this study, which was autologous stem autologous HCT for Cooperative Group led by CALGB, and used its Network cell transplantation multiple myeloma Collaboration. Biology of Blood and the CIBMTR Research Database to for multiple and Marrow Transplantation. devise an accrual plan that allowed myeloma 2013 Jun 1; 19(6): 858-859. Epub the trial to successfully meet its 2013 Mar 29. enrollment target after initial accrual difficulties. Details of this collaboration were published in a commentary article. Its success provides a paradigm for ensuring timely accrual to future national BMT studies.

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 1.0 Value the BMT CTN Brings to the HCT Community

Significant Findings and Impact of BMT CTN Studies BMT CTN Study Results Relevant Publications Impact / Future Outlook

QUALITY OF LIFE

0902: A Phase III Demonstrated no Exercise and stress management This trial tested modest, easily applied randomized, improvement in training prior to HCT: BMT CTN interventions in the early transplant multicenter trial physical or mental 0902. Biology of Blood and period. While lack of an effect was testing whether quality of life with Marrow Transplantation. 2014 disappointing, the trial enrolled more exercise or stress exercise training, Oct 1; 20(10): 1530-1536. Epub than 700 patients in 19 months, management stress management 2014 Jun 6. demonstrating that the BMT CTN has improves training, or combined an effective infrastructure to conduct Patient-reported physical functional status stress management studies addressing quality of life functioning predicts the success and symptoms of and exercise training issues. An ancillary analysis was of HCT (BMT CTN 0902). Cancer. autologous and compared to usual published during this reporting period 2016 Jan 1; 122(1): 91-98. Epub allogeneic care showing that a patient-reported 2015 Oct 6. recipients outcome (pre-HCT Medical Outcomes Trajectories of quality of life after Study Short Form-36 Health Survey HCT: Secondary analysis of BMT physical component summary scale) CTN 0902 data. Biology of Blood independently predicted overall and Marrow Transplantation. mortality in allogeneic HCT recipients, 2016 Nov 1; 22(11): 2077-2083. adding to the prognostic information Epub 2016 Aug 15. of currently used performance and co- Patient-reported outcomes and morbidity scores. This easily applied socioeconomic status as measure could aid in patient selection predictors of clinical outcomes and counseling. after HCT: A study from the BMT Four additional ancillary studies were CTN 0902 trial. Biology of Blood published during this reporting period, and Marrow Transplantation. in the areas of quality of life 2016 Dec 1; 22(12): 2256-2263. trajectories, socioeconomic status, Epub 2016 Aug 23. pre-transplant exercise, and Pretransplantation exercise and evaluation of the Cancer and HCT survival: A secondary Treatment Distress Quality of Life analysis of BMT CTN 0902. measure. An additional ancillary study Biology of Blood and Marrow is in progress. Transplantation. 2017 Jan 1; 23(1): 161-164. Epub 2016 Oct 11. Cancer and treatment distress psychometric evaluation over time: A BMT CTN 0902 secondary analysis. Cancer. 2017 Apr 15; 123(8): 1416-1423. Epub 2016 Nov 28.

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 1.0 Value the BMT CTN Brings to the HCT Community

Significant Findings and Impact of BMT CTN Studies BMT CTN Study Results Relevant Publications Impact / Future Outlook RARE DISEASES

0301: Fludarabine- Identified the optimal Fludarabine-based conditioning Optimizing transplantation regimens based conditioning dose of for marrow transplantation from for rare diseases is difficult and for allogeneic cyclophosphamide for unrelated donors in severe requires a multicenter effort. This marrow unrelated donor HCT aplastic anemia: early results of a study determined that fludarabine is transplantation in severe aplastic cyclophosphamide dose de- not sufficiently immune suppressive from HLA- anemia is less than escalation study show life- to replace cyclophosphamide in compatible 150 mg/kg threatening adverse events at conditioning regimens for unrelated unrelated donors in predefined cyclophosphamide donor transplantation for aplastic severe aplastic dose levels. Biology of Blood and anemia. Additionally, it found excess anemia Marrow Transplantation. 2012 toxicity with a commonly used dose July 1; 18(7): 1007-1011. Epub of cyclophosphamide when combined 2012 Apr 30. with fludarabine. This unexpected finding is anticipated to change Cyclophosphamide conditioning practice in many centers. A follow-up in patients with severe aplastic study for aplastic anemia patients anaemia given unrelated marrow (BMT CTN 1502) using the optimal transplantation: A Phase 1-2 cyclophosphamide dose found in this dose de-escalation study. Lancet study is released to centers. Haematology. 2015 Sept 1; 2(9): Additionally, the upcoming study will 367-375. Epub 2015 Sep 8. incorporate cord blood and haploidentical donors to reach patients who are not able to find an unrelated donor.

0803: High dose Determined that Autologous HCT for HIV-related The BMT CTN conducted this study in chemotherapy with patients with HIV- lymphoma: Results of the BMT collaboration with the AIDS autologous stem associated lymphoma CTN 0803 / AMC 071 trial. Blood. Malignancy Consortium to assess cell rescue for may successfully 2016 Aug 25; 128(8): 1050-1058. whether autologous HCT is a viable aggressive B cell undergo autologous Epub 2016 Jun 13. therapeutic option for a patient lymphoma and transplant with population frequently excluded from Hodgkin lymphoma favorable outcomes HCT clinical trials. Based on the study in HIV-infected findings, autologous transplant patients should be considered the standard of care for patients with relapsed / refractory HIV-associated lymphoma who meet standard eligibility criteria. The BMT CTN and AIDS Malignancy Consortium are also evaluating the use of allogeneic HCT for HIV-infected patients with hematological cancers and MDS in the BMT CTN 0903 trial, results of which will be presented at the 2017 ASCO Annual Meeting.

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 1.0 Value the BMT CTN Brings to the HCT Community

Significant Findings and Impact of BMT CTN Studies BMT CTN Study Results Relevant Publications Impact / Future Outlook

RARE DISEASES (continued)

0601: Unrelated Determined that a Unrelated donor cord blood This finding confirmed that using a donor reduced reduced-intensity transplantation for children with reduced-intensity regimen followed by intensity bone conditioning regimen severe sickle cell disease: results bone marrow HCT results in marrow transplant of alemtuzumab, of one cohort from the Phase II acceptable rates of engraftment and for children with fludarabine, and study from the Blood and survival but high risks of chronic severe sickle cell melphalan, followed Marrow Transplant Clinical Trials GVHD, underscoring the need for disease by bone marrow HCT Network (BMT CTN). Biology of future trials on effective GVHD resulted in low rates of Blood and Marrow prophylaxis. Additionally, early in the regimen-related organ Transplantation. 2012 Aug 1; study, there was a disappointing toxicity and a one year 18(8): 1265-1272. Epub 2012 Feb finding that using cord blood as a event-free survival of 16. stem cell source resulted in 76% but unacceptably unacceptably high levels of graft A BMT CTN Phase II trial of high rates of GVHD failure, which indicates the need for unrelated donor marrow novel transplant strategies for the Initially found that this transplantation for children with large number of sickle cell disease regimen, although severe sickle cell disease. Blood. patients who cannot find an HLA- effective for 2016 Nov 24; 128(21): 2561- matched adult donor. Two additional engraftment of bone 2567. Epub 2016 Sept 13. BMT CTN sickle cell transplant trials marrow, was are underway. One compares HLA- associated with matched bone marrow HCT to unacceptably high standard of care (BMT CTN 1503, levels of graft failure currently enrolling patients), and the after cord blood other uses haploidentical donors (BMT transplantation; this CTN 1507, to be released to centers led to the closure of early next reporting period). the cord blood cohort

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 1.0 Value the BMT CTN Brings to the HCT Community

Significant Findings and Impact of BMT CTN Studies BMT CTN Study Results Relevant Publications Impact / Future Outlook SUPPORTIVE CARE

0101: A randomized Demonstrated that Randomized double-blind trial of This study of a Phase III comparison of double-blind trial of fluconazole, a low- fluconazole versus voriconazole fluconazole and voriconazole indicates fluconazole versus cost antifungal agent, for prevention of invasive fungal that newer is not always better and voriconazole for the generally has similar infection after allogeneic that, for most patients, standard prevention of efficacy as and is hematopoietic cell fluconazole is effective fungal invasive fungal generally more cost- transplantation. Blood. 2010 Dec prophylaxis. However, an ancillary infections in effective than the 9; 116(24): 5111-5118. Epub study suggested there is a subset of allogeneic blood newer and more 2010 Sep 8. patients for whom primary antifungal and marrow expensive drug, prophylaxis with voriconazole may be Cost-effectiveness analysis of transplant voriconazole, in cost-effective, allowing more informed voriconazole compared with recipients preventing serious treatment planning by transplant fluconazole for prevention of fungal infections in the centers. invasive fungal infection in first six months after patients receiving allogeneic A pharmacokinetic ancillary study was HCT but that hematopoietic cell transplants. published this reporting period. Given voriconazole may be American Journal of Health- the small number of patients with cost-effective for those System Pharmacy. 2013 Sept 1; invasive fungal infections, it was undergoing an 70(17): 1518-1527. difficult to draw definitive conclusions. allogeneic HCT for AML Voriconazole pharmacokinetics following HCT: Results from the BMT CTN 0101 Trial. Journal of Antimicrobial Chemotherapy. 2016 Aug 1; 71(8): 2234-2240. Epub 2016 Apr 27.

0403: A Phase III, Showed no increase in A randomized double-blind, This study failed to show an randomized double- response with the placebo-controlled trial of advantage for etanercept and blind, placebo addition of etanercept soluble tumor necrosis factor highlighted the decreasing incidence controlled trial of to corticosteroids in receptor: Enbrel (etanercept) for of idiopathic pneumonia syndrome in soluble tumor the treatment of the treatment of idiopathic an era of reduced conditioning necrosis factor idiopathic pneumonia pneumonia syndrome following regimen intensity and better receptor: Enbrel syndrome; however, allogeneic stem cell diagnostic tests for infectious (etanercept) for the the reduced sample transplantation: Blood and pathogens. treatment of acute size (34 instead of 120 Marrow Transplant Clinical Trials non-infectious patients) precluded a Network protocol. Biology of pulmonary definitive conclusion Blood and Marrow dysfunction Transplantation. 2014 Jun 1; (idiopathic 20(6):858-864. Epub 2014 Mar 7. pneumonia syndrome) following allogeneic stem cell transplantation

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 1.0 Value the BMT CTN Brings to the HCT Community 1.5 Biorepository and Clinical Trial Data Resources The Network’s Research Sample Repository is a valuable resource. To date, protocols have yielded a biological research sample collection of more than 390,000 stored specimens provided by more than 6,160 subjects. An inventory of BMT CTN research samples collections is available on the Network’s public website as a resource for investigators planning correlative and ancillary studies. This website section summarizes the planned sample collection schedules and sample processing, and it lists biological samples available for all BMT CTN studies by time point and sample type. Clinical trial outcome data associated with completed trials represent another resource for investigators who want to examine research objectives other than those addressed in the original trials. General patient and clinical characteristics summaries and case report forms for completed trials are provided on the Network’s public website to assist in the development of secondary data analyses. Analyses and published results using data derived from the analysis of biorepository samples and associated trial outcome data are listed, along with other ancillary studies, in Tables 4.2a and 4.2b. 1.6 Network Efficiency Over the past several years, initiatives were undertaken to improve Network efficiency. These included creating an Activation Task Force to evaluate performance and make recommendations to improve processes, reevaluating the protocol development process, and implementing a shorter study development timeline. New practices were implemented because of these initiatives. During this reporting period, the DCC evaluated time point data to assess Network performance as part of its continuous process improvement process. Figure 1.2. BMT CTN median milestone timeframes in previous vs. current grant cycles

Protocol Team Formation to PRC Submission 2001-2009 2011-2016 PRC Submission to DSMB Approval

DSMB Approval to Protocol Release to Centers

Protocol Release to Centers to Study Activation

Protocol Release to Centers to First Patient Enrollment

Protocol Team Formation to Protocol Release to Centers

Protocol Team Formation to Study Activation

Protocol Team Formation to First Patient Enrollment

Evaluable Data to Manuscript Submission

0.0 3.0 6.0 9.0 12.0 15.0 18.0 21.0 24.0 Months

Acronyms: PRC = Protocol Review Committee, DSMB = Data and Safety Monitoring Board

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 1.0 Value the BMT CTN Brings to the HCT Community

Data in Figure 1.2 represent the median Network milestone times for BMT CTN-led studies. Two comparative timeframes are shown: 2001-2009 (previous BMT CTN grant cycles) and 2011-2016 (current BMT CTN grant cycle). The data show a decrease in times for every category except two:  Data and Safety Monitoring Board approval to protocol release to centers increased from 1.5 to 2.9 months due to 4 studies that were not released until more than 7 months after approval because of difficulty in contracting with the companies providing drug and support, additional FDA-mandated training requirements for vaccine manufacture, and/or a protocol amendment prior to release.  Evaluable data to manuscript submission for primary results manuscripts increased from 7.8 to 10.1 months due to 3 manuscripts that each took more than a year to submit. When comparing milestone data from the previous reporting period to this one, all categories are nearly equivalent. However, there are slight increases in two areas that are of concern: time to activation and time to publication. Upon evaluation, two causes were identified: contracting delays with industry partners delaying protocol activation and the extensive data adjudication process delaying publication. Two Task Forces were convened this reporting period to address these issues:  The Contracting Task Force includes members from industry, an NCI National Clinical Trials Network group, a non-profit organization that collaborates on cancer clinical trials with industry, and transplant center and DCC physicians and staff members. This group is charged with evaluating the relationship between the Network and industry to identify opportunities to enhance partnerships and streamline processes when undertaking a study together. Examples include not only contracting language and timelines but also other areas, including budget, trial management activities, and roles and responsibilities.  The Data Adjudication Task Force includes transplant center investigators as well as DCC physicians, statisticians, and staff members. Their charge is to assess whether the data adjudication process impacts trial results. This assessment includes evaluation of data updated during the adjudication process, timelines, and cost. The Task Forces will complete their assessment and provide recommendations to the Steering Committee during the next reporting period. 1.7 Funding Leverage BMT CTN leadership understands that optimizing external funding is critical at any time but particularly in the current economic environment. The Network works hard to leverage NIH support with public-private partnerships that provide both direct and in-kind contributions. The DCC develops relationships and contracts with pharmaceutical and biotechnology companies and laboratory vendors for additional budgetary support and for drugs used in studies, always with proper attention paid to avoid potential conflicts of interest. This year, the following supplemental support activities took place:  BMT CTN 1302: Multicenter Phase II, placebo controlled trial of maintenance ixazomib after allogeneic hematopoietic stem cell transplantation for high risk multiple myeloma. o An agreement was fully executed with Millennium Pharmaceuticals, Inc. to provide funding in the amount of $1.15 million as well as in kind contributions of ixazomib, bortezomib, and placebo. o Millennium Pharmaceuticals, Inc. agreed to provide additional funding in the amount of $290,000 for minimal residual disease testing. The revised funded amount will total $1.44 million.  BMT CTN 1401: Phase II multicenter trial of single autologous hematopoietic cell transplant followed by lenalidomide maintenance for multiple myeloma with or without vaccination with dendritic cell / myeloma fusions.

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 1.0 Value the BMT CTN Brings to the HCT Community

o A grant was awarded to Beth Israel Deaconness Medical Center from the Multiple Myeloma Research Foundation in the amount of $779,995 to support BMT CTN 1401.  BMT CTN 1503: A study to compare bone marrow transplantation to standard care in adolescents and young adults with severe sickle cell disease o Emory University received an R01 from NHLBI in the amount of $6.98 million to fully fund BMT CTN 1503.  BMT CTN 1506: A multi-center, randomized, double-blind, placebo-controlled Phase III trial of the FLT3 inhibitor gilteritinib administered as maintenance therapy following allogeneic transplant for patients with FLT3/ITD AML. o A Letter of Agreement was executed with Astellas Pharma Global Development, Inc. for $2.1 million to fund protocol development and study development. A contract is in the final stages of negotiation with Astellas to fully fund the trial, including providing gilteritinib and placebo.  BMT CTN 1602: A Phase II, randomized, double-blind, placebo-controlled study evaluating treatment of high risk acute graft-versus-host disease with filgotinib and corticosteroids. o A Protocol Development Agreement was placed with Gilead Sciences, Inc. for $452K to fund protocol development and study development. A contract is being negotiated to fully fund the study and to provide filgotinib.  BK virus study concept. o A Protocol Development Agreement was placed with Viracyte, LLC Sciences, Inc. for $185K for a T cell therapy for BK viral infections study. This is to fund initial protocol development. A contract will be negotiated to further fund the study if approved by the Steering Committee. All non-government third party contributions are made through a government approved Agreement, executed with the contributor. The total of all non-BMT CTN core funding additions has increased the effective investment from NIH by more than $380 million. 1.8 Key Collaborations As highlighted throughout this report, the BMT CTN fosters successful collaborations with other NIH Institutes, Networks / Consortia, and organizations:  AIDS Malignancy Consortium;  The Alliance for Clinical Trials in Oncology (formerly CALGB);  Canadian Blood and Marrow Transplant Group;  Centers for Disease Control and Prevention Office of Minority Health & Health Disparities;  Children’s Oncology Group (COG);  Dana-Farber Cancer Institute (DFCI) / Intergroupe Francophone du Myelome (IFM);  Deutsche Knochenmarkspenderdatei (DKMS) – German Bone Marrow Donor Center;  Eastern Cooperative Oncology Group (ECOG) – American College of Radiology Imaging Network (ACRIN) Cancer Research Group;  National Institute on Minority Health and Health Disparities;  NCI National Clinical Trials Network;  NCI-sponsored Cancer Trials Support Unit;  NIAID;  Office of Rare Diseases Research;  Pediatric Blood and Marrow Transplant Consortium (PBMTC);  Sickle Cell Disease Clinical Research Network;  SWOG.

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 2.0 Organizational Overview 2.0 Organizational Overview

The BMT CTN is comprised of a network of organizations that work together to achieve common goals. It includes the following elements, each of which is described in this section:  Data and Coordinating Center (Section 2.1);  Twenty Core Centers / Consortia (Section 2.2.1);  Affiliate Centers (Section 2.2.2);  Steering Committee (Section 2.3.1);  Protocol Teams (Section 2.3.2);  Technical Committees (Section 2.3.3);  Administrative Committees (Section 2.3.4);  Ad Hoc Committees (Section 2.3.5);  Review Committees (Section 2.3.6). 2.1 Data and Coordinating Center The DCC is managed by three organizations with extensive HCT research expertise: the CIBMTR, the National Marrow Donor Program® (NMDP)/Be The Match®, and The Emmes Corporation (a contract research organization). Together they are responsible for maintaining continuity of operations and effective communication, data management, and statistical support for the Network. Figure 2.1 illustrates the DCC’s relationship to the organization as a whole, which is explained more fully in Section 3. Figure 2.1. BMT CTN organizational structure

NHLBI & NCI Datta and Saffetty Prrottoccoll Reviiew Moniittorriing Commiittttee Boarrd

20 Corre Clliiniicall BMT CTN Centterrss / Steering Conssorrttiia Committee

Scientific Executive Protocol Administrative Technical Advisory Committee Teams Committees Committees Committees

Affffiilliiatte Clliiniicall DCC Centterrss

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 2.0 Organizational Overview 2.2 Clinical Centers 2.2.1 Core Centers The BMT CTN has 20 Core Clinical Centers (Table 2.1), some of which are consortia of two or more centers. Each Core Center holds a cooperative agreement with the NHLBI to participate in the BMT CTN. These centers were chosen based on the scientific merit of their grant applications to the NIH as well as evidence of their ability to collaborate in carrying out the Network mission of developing and completing high-quality trials as efficiently as possible. Table 2.1. Core Centers and Principal Investigators

BMT CTN Core Centers and Principal Investigators

Center Principal Investigator Baylor College of Medicine / Methodist Hospital (Consortium) 1. Helen Heslop, MD, DSc (Hon) 1. Baylor College of Medicine / Methodist Hospital 2. Catherine Bollard, MBChB, MD 2. Children’s National Medical Center Case Western Reserve University Ireland Cancer Center (Consortium) 1. Hillard Lazarus, MD 1. Case Medical Center 2. Richard Maziarz, MD 2. Oregon Health Sciences University 3. Ronald Sobecks, MD 3. Cleveland Clinic 4. Michael Craig, MD 4. West Virginia University City of Hope National Medical Center Ryo Nakamura, MD Dana Farber / Partners in Cancer Care (Consortium) 1. Brigham & Women’s Hospital Joseph Antin, MD 2. Massachusetts General Hospital 3. Boston Children’s Hospital Duke University Medical Center Joanne Kurtzberg, MD

Fred Hutchinson Cancer Research Center Frederick Appelbaum, MD

H. Lee Moffitt Cancer Center Claudio Anasetti, MD

Johns Hopkins University Oncology Center Richard Jones, MD

Memorial Sloan-Kettering Cancer Center Sergio Giralt, MD

Northside Hospital Atlanta Asad Bashey, MD, PhD Ohio State University Comprehensive Cancer Center (Consortium) 1. Steven Devine, MD 1. Ohio State University 2. Philip McCarthy, MD 2. Roswell Park Cancer Institute Theresa Hahn, PhD 3. University of North Carolina 3. Thomas Shea, MD 4. University of California-San Francisco 4. Lloyd Damon, MD 5. Virginia Commonwealth University 5. John McCarty, MD PBMTC (Pediatric Blood & Marrow Transplant Consortium) Michael Pulsipher, MD 47 pediatric centers in the US and Canada (see Table 2.2)

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 2.0 Organizational Overview

BMT CTN Core Centers and Principal Investigators

Center Principal Investigator

Stanford Hospital and Clinics Robert Lowsky, MD University of Florida College of Medicine (Consortium) 1. John Wingard, MD 1. University of Florida 2. Edmund Waller, MD, PhD 2. Emory University University of Michigan Medical Center Consortium 1. Gregory Yanik, MD, MS 1. University of Michigan 2. William Hogan, MBBCh 2. Mayo Clinic Mark Litzow, MD 3. Mount Sinai Hospital 3. John Levine, MD 4. Vanderbilt University 4. Madan Jagasia, MBBS, MS University of Minnesota Daniel Weisdorf, MD University of Nebraska Medical Center (Consortium) 1. Julie Vose, MD, MBA 1. University of Nebraska 2. Joseph McGuirk, DO 2. University of Kansas University of Pennsylvania Hospital Edward Stadtmauer, MD

University of Texas MD Anderson Cancer Center Amin Alousi, MD

Washington University Peter Westervelt, MD, PhD

Table 2.2. PBMTC Centers that have participated in BMT CTN studies PBMTC Centers that have Participated in BMT CTN Studies Center Location All Children's Hospital St Petersburg, FL Ann and Robert H. Lurie Children's Hospital of Chicago Chicago, IL British Columbia Children’s Hospital Vancouver, Canada Cardinal Glennon Children's Medical Center – Saint Louis University St. Louis, MO CancerCare Manitoba Winnipeg, Canada Carolinas Medical Center / Levine Children's Hospital Charlotte, NC Children's Healthcare of Atlanta Atlanta, GA Children’s Hospital at Oakland Oakland, CA Children's Hospital Los Angeles Los Angeles, CA Children's Hospital of Denver Denver, CO Children's Hospital of New Orleans New Orleans, LA Children's Hospital of Philadelphia Philadelphia, PA Children's Medical Center of Dallas Dallas, TX

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 2.0 Organizational Overview

PBMTC Centers that have Participated in BMT CTN Studies Center Location Children's Mercy Hospital and Clinics Kansas City, MO Children's National Medical Center Washington, DC Cincinnati Children's Hospital Medical Center Cincinnati, OH Columbia University Medical Center New York, NY Cook Children's Medical Center Fort Worth, TX Hackensack University Medical Center Hackensack, NJ Hopital Sainte-Justine Montreal, Canada Karmanos Cancer Institute / Children’s Hospital of Michigan Detroit, MI Mattel Children’s Hospital at UCLA Los Angeles, CA Medical University of South Carolina Charleston, SC McGill University Montreal, Canada Midwest Children's Cancer Center Milwaukee, WI Nationwide Children's Hospital Columbus, OH Nemours / Alfred I. DuPont Hospital for Children Wilmington, DE Nemours Children’s Clinic Jacksonville, FL New York Medical College Valhalla, NY Oregon Health and Science University Portland, OR Penn State College of Medicine Hershey, PA Phoenix Children's Hospital Phoenix, AZ Primary Children's Medical Center Salt Lake City, UT Riley Hospital for Children-Indiana University Indianapolis, IN Texas Transplant Institute San Antonio, TX The Steven and Alexandra Cohen Children's Hospital of New York New Hyde Park, NY University of California Los Angeles Los Angeles, CA University of California San Francisco School of Medicine San Francisco, CA University of Alabama at Birmingham Birmingham, AL University of Iowa Hospital and Clinics Iowa City, IA University of Louisville / Kosair Children's Hospital Louisville, KY University of Miami Miller School of Medicine – Sylvester Cancer Center Miami, FL University of Mississippi Medical Center Jackson, MS University of Rochester Medical Center Rochester, NY University of Texas Southwestern Medical Center Dallas, TX Vanderbilt University Nashville, TN Washington University / St. Louis Children’s Hospital St. Louis, MO

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 2.0 Organizational Overview 2.2.2 Affiliate Centers The BMT CTN has almost 70 Affiliate Centers (Table 2.3) that accrue patients to Network trials. About 18% of the BMT CTN’s overall accrual comes from Affiliate Centers. Accrual from Affiliate Centers decreased throughout the years as more Affiliate Centers have become Core Centers, either individually or as part of a Consortium. The Network encourages and facilitates broad participation of the HCT community through its Affiliate Center system. Affiliate Centers participate in one or more BMT CTN trials through individual contracts with the DCC. Applications for participation in Network trials are available online at bmtctn.net. Table 2.3. Affiliate Centers BMT CTN Affiliate Centers Center Location Advocate Lutheran General Hospital Park Ridge, IL Arizona Cancer Center / University of Arizona Tucson, AZ Aurora St. Luke’s Medical Center Milwaukee, WI Avera Hematology & Transplant Center Sioux Falls, SD Baylor University Medical Center Dallas, TX Beth Israel Deaconess Medical Center Boston, MA Cancer Centers of the Carolinas Greenville, SC Cancer Institute of New Jersey / Robert Wood Johnson University New Brunswick, NJ Children’s Hospital Los Angeles Los Angeles, CA Christiana Care Health System Newark, DE Colorado Blood Cancer Institute Denver, CO Columbia University Medical Center New York, NY Florida Hospital Cancer Institute Orlando, FL Fox Chase - Temple University BMT Program Philadelphia, PA Hackensack University Medical Center Hackensack, NJ Henry Ford Health System Detroit, MI Hopital Saint-Louis Paris, France Indiana BMT Clinics Beech Grove, IN Indiana University Medical Center / Riley Hospital Indianapolis, IN Intermountain BMT Program Salt Lake City, UT Jewish Hospital BMT Program Cincinnati, OH Kansas City Cancer Centers Kansas City, MO Kapi'olani Medical Center for Women and Children – University of Honolulu, HI KarmanosHawaii Cancer Institute Detroit, MI Loyola University Medical Center Maywood, IL Mayo Clinic Arizona Phoenix, AZ

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 2.0 Organizational Overview

BMT CTN Affiliate Centers Center Location Mayo Clinic Florida Jacksonville, FL Medical College of Wisconsin Milwaukee, WI Medical University of South Carolina Charleston, SC Montefiore Medical Center Bronx, NY Nashville VA Medical Center Healthcare Nashville, TN National Cancer Institute - NIH Bethesda, MD North Shore University Hospital Manhasset, NY Northwestern University Chicago, IL Penn State College of Medicine - The Milton S. Hershey Medical Center Hershey, PA Providence Portland Medical Center Portland, OR Rush University Medical Center Chicago, IL Sarah Cannon BMT Program Nashville, TN Spectrum Health Grand Rapids, MI St. Louis University St. Louis, MO Stony Brook University Medical Center Stony Brook, NY SUNY Upstate Medical University Syracuse, NY Texas Transplant Institute San Antonio, TX Tom Baker Cancer Center / University of Calgary Calgary, AB Tufts Medical Center Boston, MA University of Alabama at Birmingham Birmingham, AL University of California Los Angeles Los Angeles, CA University of California San Diego Medical Center La Jolla, CA University of Chicago Chicago, IL University of Illinois Chicago, IL University of Iowa Hospitals and Clinics Iowa City, IA University of Kentucky Lexington, KY University of Maryland Medical Systems - Greenebaum Cancer Center Baltimore, MD University of Massachusetts / Memorial Medical Center Worcester, MA University of Miami Miami, FL University of Oklahoma Medical Center Oklahoma City, OK University of Pittsburgh Cancer Institute Pittsburgh, PA University of Rochester Medical Center (Adults and Pediatric) Rochester, NY University of Texas Southwestern Medical Center Dallas, TX University of Virginia Charlottesville, VA

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 2.0 Organizational Overview

BMT CTN Affiliate Centers Center Location University of Wisconsin Hospital & Clinics Madison, WI Utah BMT / University of Utah Medical School Salt Lake City, UT Wake Forest University Health Sciences Winston-Salem, NC Weill Cornell Medical College / New York Presbyterian Hospital New York, NY Western Pennsylvania Cancer Institute Pittsburgh, PA Yale University School of Medicine / Yale-New Haven Hospital New Haven, CT

2.3 Committee Structure The BMT CTN committee structure ensures the Network works toward common goals. Each committee is described in this section. 2.3.1 Steering Committee The Steering Committee consists of the Principal Investigator of each Core Center or Consortium, the DCC Principal Investigator and Co-Principal Investigators, the NHLBI Project Officer, the NCI Project Officer, a representative of each of the NCI-funded National Clinical Trials Network Groups, and representatives of Affiliate Centers that meet standards for exemplary accrual and participation in BMT CTN trials. Other members of the DCC, Core Centers, and NIH regularly participate in Steering Committee meetings. The Steering Committee roster is listed in Attachment A1. The Steering Committee sets the scientific agenda and oversees the selection, design, execution, and analysis of all BMT CTN studies. The Committee ensures the most relevant studies are chosen, they are appropriately designed and executed, and data analyses are properly conducted. Additionally, the Steering Committee works in collaboration with the DCC to ensure participating transplant centers adhere to BMT CTN policies and procedures. The Committee also resolves any operational issues raised by investigators, Clinical Research Associates, laboratory and repository staff, DCC members, or others. The Steering Committee selects a Committee Chair who first serves a two-year term as Vice-Chair, then a one year term as Chair-Elect, followed by a two-year term as Chair, and finally a one-year term as Immediate Past- Chair. Steven Devine, MD, Ohio State University Medical Center, began a two-year term as Chair on January 1, 2016. Richard Jones, MD, Johns Hopkins University, is the Chair-Elect, and Helen Heslop, MD, DSc (Hon), Baylor College of Medicine, is the Vice-Chair. 2.3.2 Protocol Teams Each Protocol Team consists of one to four Chairs; at least three co-investigators from Core and Affiliate Centers; an NHLBI and/or NCI representative; an NHLBI Statistician; and a DCC Protocol Officer, Coordinator, Statistician, and Contracts Representative. A Protocol Team is formed when a proposal is accepted by the Network. This team develops the study concept into a working study design and provides scientific oversight for the trial throughout its life cycle. The Protocol Team also:  Reviews applications for participation from Affiliate Centers;  Develops patient and physician educational materials;  Monitors accrual and compliance with protocol requirements;  Prepares amendments as necessary;

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 2.0 Organizational Overview

 Reviews endpoint data for accuracy and consistency;  Analyzes and interprets study data;  Prepares manuscripts. 2.3.3 Technical Committees Standing and ad hoc Technical Committees generally consist of a maximum of nine members who are not associated with the DCC or NIH. Each Technical Committee is also assigned one or more NHLBI and NCI representatives and one or more DCC staff members. These committees conduct specified functions of Network activity, advise the Steering Committee on certain Network policies and procedures, and provide technical expertise to protocol design. All standing Technical Committees must review each protocol before they are distributed to centers for implementation. During this reporting period, the Technical Committees reviewed one new protocol (BMT CTN 1602). Committee members are appointed by the Executive Committee to three-year terms. Nominations are open to participating Core and Affiliate centers. A Nominating Committee reviews the nominations and proposes a slate of candidates. These candidates are approved by the Executive and Steering Committees. 2.3.3.1 Biomarkers Committee The Biomarkers Committee, which is made up of Core and Affiliate Center transplant physicians, was formed to:  Inform the Network’s scientific agenda with a focus on questions involving analysis of biologic specimens for genomic and proteomic markers;  Review new and existing studies for opportunities to collect blood and tissue samples for analysis of potential prognostic markers;  Advise the Network protocol teams in their review of ancillary study proposals that request the use of BMT CTN research samples. The current Biomarkers Committee roster is listed in Attachment A2. During this reporting period, the Biomarkers Committee provided input on BMT CTN 1202 (Biomarkers study) procedures to the BMT CTN DCC and Executive Committee, 1202 Protocol Team, and 1202 Endpoint Review Committee members. The finalized procedures are associated with:  Management of the 1202 biospecimen / clinical data collection;  Submission of ancillary laboratory study proposals;  Adjudication and final approval of meritorious studies. The Biomarkers Committee will play a lead role in the review, prioritization, and approval of 1202 ancillary studies submitted to the BMT CTN. Final review and approval of proposals, together with Biomarkers Committee comments and recommendations, will be conducted by the BMT CTN Executive Committee. 2.3.3.2 Clinical Research Associates Committee The Clinical Research Associates Committee consists of Clinical Research Associates and Data Managers from Core and Affiliate Centers. This committee:  Reviews each BMT CTN protocol before it is distributed to centers, focusing on reviewing and resolving logistical issues (e.g., shipping and receipt of specimens or drugs);  Assists in developing and reviewing Case Report Forms;  Reviews educational materials for use at participating clinical centers;  Provides input for the BMT CTN Coordinators’ meeting held during the BMT Tandem Meetings. The current Clinical Research Associates Committee roster is listed in Attachment A3.

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 2.0 Organizational Overview

During this reporting period, the Clinical Research Associates Committee reviewed Case Report Forms for eight protocols (1101, 1301, 1401, 1501, 1502, 1503, 1506, and 1507) and three new core forms for use in all protocols. In addition, the Committee provided feedback on several ancillary items:  Logistics of tracking the screening of potential patients for BMT CTN 1503 and collection of these data;  Value of collecting patient namecode in the data system from a clinic coordinator’s perspective. 2.3.3.3 Pharmacy Committee The Pharmacy Committee consists of pharmacists from Core and Affiliate Centers. It reviews BMT CTN protocols for appropriate use and administration of pharmaceuticals. It also advises Protocol Teams about possible pharmacokinetic or other ancillary studies. The current Pharmacy Committee roster is listed in Attachment A4. 2.3.3.4 Special Populations Committee The Special Populations Committee consists of pediatric and adult transplant physicians from Core and Affiliate Centers. It ensures that children, women, and minority study participants are considered for inclusion in all appropriate investigational protocols developed by the Network. It also ensures that, for studies involving pediatric participants, appropriate modifications are addressed in informed consent, patient care, and monitoring documents. The current Special Populations Committee roster is listed in Attachment A5. Evaluation of HCT in the pediatric population presents some unique challenges. The Network is committed to developing strategies to address these challenges and increase the participation of children in HCT clinical trials. Eighteen Network trials have enrolled or are enrolling children (BMT CTN 0101, 0201, 0301, 0302, 0402, 0501, 0601, 0603, 0604, 0801, 0802, 0803, 0903, 1202, 1204, 1301, 1501, and 1503); three of them focused specifically on pediatric issues (BMT CTN 0501, 0601, and 1204). Two upcoming protocols also include children / adolescents (1502 and 1507), including one study for aplastic anemia patients and one for patients with sickle cell disease. The proportion of BMT CTN trial participants under age 16 is only slightly lower than the overall proportion in the US transplant population. Since many US pediatric HCT recipients also have access to HCT trials through the COG, Network leadership feels these enrollment figures are appropriate. 2.3.3.5 Toxicity and Supportive Care Committee The Toxicity and Supportive Care Committee consists of Core and Affiliate Center transplant physicians. This committee:  Works with the DCC to define methods for evaluating adverse events and toxicities after transplantation;  Reviews the evaluation and monitoring requirements for toxicities on BMT CTN protocols;  Designs and approves forms and procedures for collecting toxicity data, including standards for expedited reporting of certain adverse events. The current Toxicity and Supportive Care Committee roster is listed in Attachment A6. 2.3.4 Administrative Committees 2.3.4.1 Executive Committee The Executive Committee consists of the Steering Committee Chair, Chair-Elect or Immediate Past-Chair, and Vice-Chair; NHLBI and NCI Project Officers; and DCC Principal Investigator and Co-Principal Investigators. The Executive Committee is a subcommittee of the Steering Committee and works in collaboration with the DCC. Executive Committee members are indicated by an asterisk (*) in Attachment A1. The Executive Committee ensures participating transplant centers adhere to BMT CTN policies and procedures,

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 2.0 Organizational Overview and it works together with the Steering Committee to resolve operational issues raised by investigators, Clinical Research Associates, laboratory and repository staff, members of the DCC, and others. It appoints Technical and Administrative Committee members. The Executive Committee also:  Addresses policy making issues;  Reviews contractual arrangements and financial matters affecting the Network as a whole;  Makes recommendations to the Steering Committee;  Reviews and approves Transplant Center Performance Reports, audits, and corrective action plans;  Provides initial review of research proposals submitted to the BMT CTN for new trials and ancillary studies;  Assists in developing Steering Committee meeting agendas. 2.3.4.2 Publications, Abstracts, and Presentations Committee The Publications, Abstracts, and Presentations Committee consists of Core and Affiliate Center transplant physicians. This committee develops publication and presentation policies. It also reviews publications and presentations to ensure confidentiality of study participants and proprietary information as well as to ensure appropriate acknowledgements of contributions, sponsorship, and authorship. During this reporting period, the Committee reviewed 5 abstracts and 12 manuscripts. Publications Committee members are appointed by the Executive Committee using the same nomination process as described above. The current Publications, Abstracts, and Presentations Committee roster is listed in Attachment A7. 2.3.5 Ad Hoc Committees Additional administrative and technical committees are convened as needed. For example, a Nominating Committee is formed to propose candidates for open committee positions.  Scientific Advisory Committees. As a result of the Network’s 2007 State of the Science Symposium (Section 6.2.1), 12 Scientific Advisory Committees were formed to address specific areas pertinent to HCT trials. The Committees were redesigned and reconvened to plan for the 2014 State of the Science Symposium (Section 6.2.2). After the conclusion of each State of the Science Symposium, the committees continued to operate and meet on an ad hoc basis to review and prioritize the Network’s scientific agenda. In the summer of 2011, the committees reviewed and summarized protocol concepts submitted by Core Center applicants for discussion at the July Steering Committee Meeting, the first meeting with new Core Center representatives. During this reporting period, the process was undertaken again, and the Committees are scheduled to review new concepts to be presented at the June 2017 Steering Committee meeting in preparation for the start of the next grant cycle on July 1, 2017 (Section 6.1). 2.3.6 Review Committees Three independent Review Committees provide additional oversight for BMT CTN trials:  Protocol Review Committee. The Protocol Review Committee is appointed by the NHLBI and consists of a Chairperson and Members whose experience reflect areas of expertise necessary to evaluate the scientific merit and design of BMT CTN protocols. Consultants may be added on an ad hoc basis if needed. The Protocol Chair (or designee), Protocol Officer, Statistician, and senior members of the DCC represent the Protocol Team at Protocol Review Committee meetings.  Two Data and Safety Monitoring Boards. The two Data and Safety Monitoring Boards are independent boards appointed by the NHLBI and/or NCI. Each is composed of a Chair and Members with expertise in biostatistics, clinical trials, bioethics, and the specific research area(s) of the Network studies. Consultants may be added on an ad hoc basis if needed. Each Board handles about half of the Network portfolio.

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 3.0 Administrative Functions of the DCC

3.0 Administrative Functions of the DCC

The DCC is a collaborative partnership of three organizations with extensive experience in multicenter, HCT- related clinical research. The DCC is led by Mary Horowitz, MD, MS, CIBMTR; Adam Mendizabal, PhD, The Emmes Corporation; and Dennis Confer, MD, NMDP/Be The Match. The DCC supports and manages the efficient development, implementation, and completion of high-quality Phase II and III clinical trials for the Network, including:  Evaluating and prioritizing study concepts;  Developing protocols with appropriate statistical designs;  Activating studies and developing plans to accrue patients in a timely manner;  Monitoring for safety, regulatory, and protocol compliance as well as data accuracy;  Collecting complete clinical and laboratory data;  Analyzing and sharing research results. The DCC also coordinates and supports overall BMT CTN activities to enhance Network effectiveness, including:  Maintaining the Administrative and Technical Manuals of Procedures;  Facilitating communication and maintaining public and private websites;  Maintaining a state-of-the-art research database;  Maintaining systems for acquisition and storage of biologic specimens;  Facilitating study completion, and publishing results in a timely manner;  Managing contractual arrangements and fiscal activities;  Monitoring and improving overall center performance;  Supporting all Network committees and activities with meeting planning and other logistical support;  Collaborating with government organizations to avoid competing studies and foster intra-group participation. 3.1 DCC Partner Organizations The DCC consists of three partners:  CIBMTR (Milwaukee, Wisconsin, and Minneapolis, Minnesota) is a research organization formed in 2004 from the affiliation of the International Bone Marrow Transplant Registry at the Medical College of Wisconsin (MCW) and the Research Department of NMDP/Be The Match. The CIBMTR has a proven history of clinical research and publication in both HCT and statistical methodology. It has fostered effective collaborations with a large network of transplant centers. It also maintains an extensive observational research database of virtually all allogeneic transplantations and most autologous transplantations performed in the US.  The Emmes Corporation (Rockville, Maryland) is a contract research organization established in 1978 that has managed more than 1,000 Phase I-IV trials and registries in 60 countries on 6 continents. Emmes provides experience in planning, implementing, and managing multicenter clinical trials in a variety of areas, including HCT, statistical design and analysis, clinical trial design and management, complex data collection system design and implementation, site monitoring, and regulatory support.  NMDP/Be The Match (Minneapolis, Minnesota) was established in 1987. It is the world leader in HCT donor registry and graft procurement management, and it operates the world’s largest HCT-related Research Sample Repository. NMDP/Be The Match has a large network of donor, collection, and transplant centers as well as cord blood banks; a skilled Contracts and Procurement Department that manages contracts with 177 US and international transplant centers and maintains contractual 31

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 3.0 Administrative Functions of the DCC

relationships with specimen repositories and contract laboratories; an experienced Patient and Health Professional Services department that provides educational and counseling services to patients in need of a transplant; and a Case Management department that facilitates most of the unrelated donor transplantations performed in the US. Figure 3.1 illustrates the relationship among DCC organizations and its distribution of responsibilities, and Table 3.1 describes the specific responsibilities of each DCC member. Figure 3.2 displays the organizational structure of the DCC. Figure 3.1. DCC organization

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 3.0 Administrative Functions of the DCC

Table 3.1. Responsibilities of DCC members NMDP/Be DCC Member Responsibilities CIBMTR Emmes The Match Administrative Functions Provide overall scientific /administrative leadership Lead Develop statistical methodology1 Shared Shared Recruit, manage, and train pool of physician Medical Monitors Lead Develop Manuals of Procedures / Standard Operating Procedures (SOPs) Lead Facilitate meeting logistics (including site location, travel arrangements, Lead conference calling, travel reimbursement) Coordinate meeting materials2 Shared Shared Manage general and study-specific electronic communications (including Lead clinicaltrials.gov posting, numbered memoranda, websites) Maintain master rosters Lead Prepare protocol budgets and track protocol-specific financials Lead Monitor overall budget and subcontracts Lead Trials Development & Management Develop / review concepts3 Shared Shared Shared Develop protocols3 Shared Shared Shared Protocol Team Serve as Protocol Officer Lead Serve as Protocol Statistician1 Shared Shared Serve as Protocol Coordinator Lead Protocol Implementation Manage protocol document and all amendments Lead Identify centers Lead Qualify centers (certify centers’ ability to execute protocol) Lead Contract with centers Lead Identify and contract laboratories / repositories Lead Template regulatory forms (1572, financial disclosure, site delegation log) Lead Manage data management system (including registration, Web-based data entry, Lead database design, study archive backup, contingency plans) Develop Case Report Forms Lead Coordinate laboratory and repository functions Lead Manage investigational product distribution4 Shared Shared Prepare and submit IND/IDE applications and reports to the FDA Lead Prepare materials and provide Protocol Review Committee and Data and Safety Lead Monitoring Board meeting support Manage site activation process Lead Train site personnel Lead

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 3.0 Administrative Functions of the DCC

NMDP/Be DCC Member Responsibilities CIBMTR Emmes The Match Develop informed consent forms and patient materials Lead Develop study-specific handbooks and/or SOPs for processes, lab samples, Shared Shared investigational product, data management5 Monitor adverse events, toxicities, and other safety endpoints Lead Develop and implement accrual plan6 Shared Shared Shared Review performance of centers7 Shared Shared Shared Monitor accrual8 Shared Shared Shared Develop monitoring plan, conduct monitoring visits, write monitoring reports, Lead and manage corrective action plans Monitor data accuracy and conduct data review sessions9 Lead Prepare reports / manuscripts / coordinate dissemination of results11 Shared Shared Shared 1 ~75% of PhD Protocol Statisticians are CIBMTR staff members and 25% Emmes staff members; Emmes MS-level statisticians provide primary support for data set preparation and Data Safety and Monitoring Board reports. CIBMTR MS-level statisticians help with data transfer, concept evaluation, accrual plans and assessment of ongoing accrual. 2 NMDP/Be The Match staff members develop agendas and supporting materials and finalize minutes for Steering and Executive Committee meetings and DCC calls; Emmes staff members develop agendas, supporting materials, and reports for the Protocol Review Committee and Data and Safety Monitoring Boards. Both organizations contribute to protocol team call agendas, materials, and minutes. 3 Key personnel from all three entities review protocol concepts. The CIBMTR provides HCT data to assess feasibility; Emmes and CIBMTR statisticians draft statistical plans. Protocol teams include a CIBMTR Protocol Officer, Emmes Protocol Coordinator, and CIBMTR or Emmes Statistician with support from Emmes Safety Monitors and from NMDP/Be The Match Contracts, Patient Services, and Immunobiology staff members. 4 NMDP/Be The Match develops and executes agreements for investigational agents. NMDP/Be The Match and Emmes work together to implement distribution of investigational agents as per the contract and project sites’ needs. 5 NMDP/Be the Match prepares study-specific handbooks and/or SOPs for lab samples and investigational products as well as patient-specific materials. Emmes prepares study-specific site SOPs and activation materials. 6 The accrual plan is drafted by the NMDP/Be The Match Project Manager / Accrual Coordinator based on projected accrual rates from Core and Affiliate Centers, data from the CIBMTR Research Database, and input from the Protocol Team. 7 Accrual, data delinquency, missing values, and data queries in AdvantageEDC (which will transition to Advantage eClinical in the next funding period), data discrepancies, and major and minor protocol violations are tracked by Emmes. NMDP/Be The Match monitors sample collections and lab testing compliance. The CIBMTR monitors data submitted via FormsNet to the CIBMTR which is not captured by AdvantageEDC. Emmes prepares annual center performance reports and NMDP/Be The Match and Emmes prepare quarterly center performance reports that are sent to Core Centers. 8 Emmes monitors and posts daily accrual to each protocol by center. The NMDP/Be The Match Project Manager / Accrual Coordinator surveys centers for estimated accrual to each study and then monitors center accrual against projections. The CIBMTR uses its Research Database to assess and address accrual issues. 9 The CIBMTR Protocol Officer also has a key role in coordinating the Endpoint Review Committee. 10 The Protocol Coordinator, Officer, and Statistician all contribute to preparation of presentations and publications. Emmes provides administrative support to the Publications Committee in its oversight of the publication process. NMDP/Be The Match Contracts staff assures proper acknowledgement of trial contributors. CIBMTR, NMDP/Be The Match and Emmes staff members coordinate, compile, and distribute the annual BMT CTN Progress Report to the research community and the public to provide them with results from presented and published studies and updated information on protocol activity.

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 3.0 Administrative Functions of the DCC

Figure 3.2. DCC organizational structure as of March 31, 2017

The Emmes Corporation CIBMTR Milwaukee NMDP / CIBMTR Minneapolis Adam Mendizabal, PhD Mary Horowitz, MD, MS Dennis Confer, MD DCC Co-Principal Investigator ^ DCC Principal Investigator ^ DCC Co-Principal Investigator

Rebecca Drexler Stephen Spellman, MBS Iris Gersten, MS Jeanette Carreras, MPH Patricia Steinert, PhD Senior Manager, Director, Immunobiology & Project Director Raphael Fraser, PhD Administrator Brent Logan, PhD Prospective Research Observational Research Waleska Perez, MPH Beth Blackwell, ScD Denise King, MS Biostatisticians Jana Dworski Alan Howard, PhD Sue Lorenz Chris Bryant, PhD Project Director Project Coordinator Principal Immunobiology Peter Dawson, PhD Grants Financial Manager Research Scientist Kavita Bhavsar Mat Makowski, PhD Veronica Garcia BMT CTN Data Coordinator Amy Tan, MS Amy Foley, MA Stephanie Waldvogel Kate Ketkaew Jessica Gillis-Smith, MPH ~ Maggie Wu, MS BMT CTN Project Immunobiology ~ Mary Magliocco Publishing Coordinator Manager Grace Zhou, MS Thomas Degen Research Scientist Iris Yu Jessica Zhu, MS Programmer Analyst Clinical Systems Analysts Statisticians Monica Williams NMDP/Be The Match Ashley Spahn Immunobiology Mita Desai Administrative Asst Support Services Kari Bingham, PharmD Research Scientist Brianne Allison Data Entry Coordinator Kristy Applegate, MS ~ Jennifer Romeril, RN ~ Kate Bickett Audra Thompson, RN Safety Monitors Mary Frey Gina Graves Elizabeth Murphy, Jamie Garrison, MS ^ Anita D’Souza, MD Director, Contracts Director, Finance EdD, RN Dylan Mawby ^ * Mary Eapen, MD & Procurement and Controller VP, Patient Services Katie Holtrop ~ Courtney Nelson ^ Mehdi Hamadani, MD ~ Ellen Parker, MBA Kelly O’Brien, PhD ^ * Marcelo Pasquini, MD Jensen Podbielski Nancy Poland, MA Jenna Dahlberg Ellen Denzen, MS Theresa Pritchard, MS ^ * Wael Saber, MD Thomas Tamura Sr Mgr, Contracts Supervisor, Sr Manager, Health Alyssa Ramirez * Liza Thiel, MD Whitney Sheffer Admin Coordinators & Procurement Contract & Award Services Research Samantha Wilkins, MA * Weiyun Ai, PhD, MD Accounting Heather Wittsack Haddi Camara-Ba * Christopher Bredeson, MD Pam Budnick Heather Moore, Katie Robart Bal Protocol Coordinators Regulatory Data Entry * Steven Deeks, MD Renee Carby, MS MPH, CHES * Dianna Howard, MD Kiila Lee Sr Accountant, Program Specialist Alex Borbely * Natasha Kekre, MD Contract Contracts & Awards Sue Isman ~ Cynthia Couture, RN * Tammy Kindwall-Keller, MD Representatives Lensa Idossa Brianna Johnson Protocol Monitor * Guenther Koehne, MD Peggy Schmidt * Gabrielle Meyers, MD Cost Accountant, Program Analyst ~ Kristin Knust, MS Susan Lahti ^ * Willis Navarro, MD Gov’t Accounting Roe Wright Michelle LaMotteo Sr Paralegal Data Managers Bill Karabelas * Eneida Nemecek, MD Programmer / Analysts ^ * Marcie Riches, MD KEY * Bipin Savani, MD Emmes Corporation, Rockville, MD ^ Protocol Officer * Shannon Smiley, MD CIBMTR, Milwaukee, WI * Medical Monitor * Angie Smith, MD NMDP/CIBMTR, Minneapolis, MN ~ Group Manager * Trisha Wong, MD, MS Various Locations

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 3.0 Administrative Functions of the DCC 3.2 Policies and Procedures The BMT CTN has two Manuals of Procedures: Administrative and Technical. The Administrative Manual includes policies and procedures related to:  Participation in Network protocols, including detailed steps for proposing, drafting, and executing studies;  Roles and duties of Core and Affiliate Centers and Network committees;  Roles of the CIBMTR, NMDP/Be The Match, and Emmes within the DCC;  Transplant center site monitoring;  Adverse event reporting;  Human subject protection and regulatory procedures;  Publications, abstracts, and presentations;  Ancillary and secondary analysis studies. The Technical Manual of Procedures is a composite of policies and procedures pertinent to practice guidelines and laboratory evaluations unique to HCT. The Technical Manual includes detailed policies and procedures regarding:  Acute and chronic GVHD;  Characterization and processing for hematopoietic cellular products;  Diagnosing and grading infectious diseases;  Technical Committees’ policies. An updated version of the Administrative Manual of Procedures was released in December 2016. The Technical Manual will be updated during the next reporting period. These manuals and other procedural documents are available on the BMT CTN public website (bmtctn.net) and a password-protected, secure website for Network members (bmtctnsp.net). 3.3 Administrative Support The DCC coordinates and schedules meetings and conference calls for the Steering, Executive, Scientific Advisory, Administrative, and Technical Committees as well as for Protocol Teams. From April 1, 2016, through March 31, 2017, the DCC managed 380 conference calls. DCC representatives attend and participate in all Network meetings, providing logistical support to ensure the meetings are conducted efficiently and effectively. Two or more DCC staff members participate on all Technical Committee and Protocol Team calls, preparing and circulating agendas and minutes for these committees. The DCC also maintains version control of protocols during development and after their approval, including all amendments. 3.4 Fiscal Planning and Contracting Support NMDP/Be The Match manages fiscal planning and contract support for the BMT CTN. Personnel from the NMDP/Be The Match Contracts and Procurement Department participate in DCC conference calls, protocol development calls, Executive and Steering Committee calls, and in-person Steering Committee meetings. NMDP/Be The Match develops and executes Requests for Proposals, service agreements, and agreements for laboratory and pharmacy services to support specific protocols. Throughout the history of the BMT CTN, and in collaboration with both NHLBI and NCI, NMDP/Be The Match has negotiated a number of contractual agreements to sponsor contributions that offset the cost of individual protocols or provide pharmaceutical products. NMDP/Be The Match has also executed agreements with each of the NCI National Clinical Trials Network Groups, fostering collaboration with groups outside the Network. On an ongoing basis, the NMDP/Be The Match Contracts and Procurement Department:

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 3.0 Administrative Functions of the DCC

 Executes Master Agreements and corresponding Clinical Study Protocol Riders for each protocol, facilitating participation of Affiliate and Core Centers in BMT CTN protocols;  Coordinates and manages the protocol budget development process, including reimbursements for protocol-specific patient costs; generates financial reports on protocol spending; and provides forecasts of future spending based on observed patterns, when requested;  Assists the protocol teams in selecting the best-performing Affiliate Centers by developing performance “snapshots” for each Affiliate Center applying to participate on a study. The snapshot shows the amount of time it takes a center to sign each rider as well as the average number of months for all BMT CTN riders; the amount of time it takes from approval to activation and the average for all BMT CTN studies; enrollment history on BMT CTN studies; and other relevant facts. 3.4.1 Cost-Saving Mechanisms The DCC carefully manages the resources of the Network. It established a uniform budgeting model to project trial costs accurately and uses a competitive bid process to procure laboratory, pharmacy, and other services, ensuring that NIH funds are used wisely. To minimize delays associated with contracting with private companies, the DCC established a policy of face-to-face meetings with potential contributors early in the protocol development process. These meetings familiarize potential contributors with the Network, its membership, and its research activities, and they allow the DCC to identify specific corporate contract liaisons. Additionally, the Steering Committee encourages Protocol Teams to consider cost-saving mechanisms such as:  Restricting study requirements, such as research repository samples, to those that are essential to answering the primary and secondary questions;  Limiting the number of secondary questions to the most scientifically important;  Reducing the length of follow-up periods and using the established CIBMTR Research Database for long term follow-up of enrolled patients beyond the primary endpoint. 3.5 Communication Managing the large Network and its protocol activity requires excellent communication. Information must flow among DCC members, Network committees, transplant centers, laboratory and repository facilities, the medical community, and the lay public. Weekly teleconferences for leadership and DCC members and monthly teleconferences for the Executive Committee are conducted. Steering Committee meetings are scheduled either in-person or by teleconference each month. Additional communication efforts are described in this section. 3.5.1 Maintaining BMT CTN Websites The DCC maintains a public website (bmtctn.net) and a secure, password-protected website (bmtctnsp.net). The Network’s public website features:  A BMT CTN organizational overview and contact information;  The current BMT CTN Progress Report;  The current State of the Science Symposium Report;  Current versions of open protocols;  Educational materials for all open protocols;  Applications to participate in BMT CTN protocols as an Affiliate Center;  Administrative and Technical Manuals of Procedures;  A list of BMT CTN publications;  A summary of the BMT CTN’s research sample collection listing biological samples available for all studies, by time point and sample type, and two summary tables: GVHD treatment trial samples and

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 3.0 Administrative Functions of the DCC

allogeneic transplant trial samples;  Links to related DCC and government partner websites;  A password-protected page for BMT CTN Principal Investigators and Coordinators that includes links to: o Data reports on site activation, accrual by site, projected accrual, demographics, missing forms summary, lab compliance (overall), monthly accrual by center, and data quality by center; o Associated websites, including the Network’s secure, password-protected website; AdvantageEDC data collection website, and GlobalTrace specimen tracking website; o AdvantageEDC and GlobalTrace training modules. The Network’s secure, password-protected website uses Microsoft SharePoint Server™ software to allow Network participants to share confidential information. It features:  Meeting materials, including agendas, minutes, and conference call materials;  Protocol Team materials, including the current version of protocols in development;  Transplant Center materials, including the official version of protocols and informed consent templates;  Rosters of personnel at participating centers;  Rosters for the Steering, Administrative, and Technical Committees as well as Protocol Teams;  Study accrual reports;  Monthly recruitment reports. The DCC uses a separate password-protected area of the secure site to post Data and Safety Monitoring Board meeting materials, share confidential information, and distribute monthly safety monitoring reports. All necessary meeting materials are posted two weeks before scheduled meetings. Adverse events reports and stopping guideline (safety) tables and graphs are posted monthly. Data and Safety Monitoring Board members can access the accrual, monthly recruitment, data quality, and site activation status reports, which are updated nightly or monthly depending on the report. The CIBMTR’s public website (cibmtr.org) has a page dedicated to the Network, including an overview of its functions, a list of all BMT CTN protocols, and a link to the BMT CTN public website. Additionally, the CIBMTR displays information about the Network and its protocols at national and international meetings. NMDP/Be The Match’s public website (bethematch.org) also has a page dedicated to the BMT CTN, including an overview of the Network and links to the BMT CTN and government partner websites. 3.5.2 Developing Patient Support and Marketing Materials NMDP/Be The Match’s Patient and Health Professional Services Department assists the Network in developing patient-friendly study materials. This department managed an extensive project to reformat the Network’s patient consent and assent forms for easier readability and comprehension. This resulted in a 2011 manuscript that summarized recommendations of the review team for the development and formatting of accessible consent forms for multicenter clinical trials (Denzen et al., Biology of Blood and Marrow Transplantation, full citation listed in Appendix B1.) The intent of these recommendations is to guide the informed consent form writing process, simplify local IRB review of consent forms, enhance patient comprehension, and improve patient satisfaction. The recommendations are being tested in a randomized study of the updated consent versus the standard format in the Easy-to-Read Informed Consent study (BMT CTN 1205). Several members of the original Patient and Health Professional Services team who revised the consent form format serve on the BMT CTN 1205 protocol team. Initial primary results from BMT CTN 1205 were presented to the Steering Committee in February 2017. Additional results and the team’s recommendation regarding consent form format for future BMT CTN studies will be presented in May 2017. The primary results manuscript will also be drafted early in the next reporting period.

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 3.0 Administrative Functions of the DCC

The Patient and Health Professional Services Department and NMDP/Be The Match Marketing and Communications Department also support communications for accrual enhancement, help develop patient education materials, and assist in the design of Network publicity materials, such as protocol flyers and posters used for national meetings and emailed accrual updates. 3.5.3 Communicating Trial Results Communicating trial results rapidly and accurately is a fundamental activity of the DCC. Efficient and accurate data collection, processing, and analysis — each stage of which is supported by the DCC — ensures the integrity of Network trials and provides the foundation for publication and dissemination of study results. For all BMT CTN primary results publications since inception, the median number of days from the DCC statistician’s dissemination of the final analysis report to manuscript submission is 233 days. The median number of days from submission to publication is 145 days. The DCC helps Protocol Teams disseminate study results and publish as quickly as possible, assisting investigators in developing study slide sets and poster presentations for national and international meetings. The DCC also provides administrative support to the Publications Committee in its oversight of the publication process and assures proper acknowledgement of trial contributors. DCC staff members coordinate, compile, and distribute the annual BMT CTN Progress Report to the research community and the public to provide them with updated information on protocol activity, including published findings. These reports are available in print and digital format, and they are posted on the Network’s public website (https://web.emmes.com/study/bmt2/ Progress%20Reports.html). 3.5.4 Social Media Engagement In June 2014, the Steering Committee approved the Social Media Task Force’s recommendations to target communications to healthcare providers via social media. The targeted audience includes those at BMT CTN Core, Consortia, and Affiliate Centers: physicians, physician assistants, nurse practitioners, pharmacists, nurses, study coordinators, data managers, statisticians, and laboratory and regulatory staff; NHLBI and NCI Project Officers; referring physicians and research staff outside the Network; related organizations [e.g. American Society of Blood and Marrow Transplantation (ASBMT), NMDP/Be The Match, ASH, American Association of Blood Banks]; and medical students. The primary goals of the BMT CTN’s adoption of social media forums are:  Visibility of the Network – increasing awareness of the BMT CTN, participating centers, and Network clinical trial portfolio and publications;  Inclusiveness – communicating with individuals at BMT CTN centers who are not included on BMT CTN distribution lists and do not attend meetings (e.g. junior investigators) as well as reaching referring hematology / oncology and community physicians;  Collaboration – engaging new, and therefore a wider variety of, voices within and outside the Network;  Education – sharing BMT CTN resources as well as linked content from other affiliated groups (e.g. ASBMT, NMDP/Be The Match, NIH). Based on the Task Force’s background research, including interviews with other similar organizations and cooperative groups, it was determined the optimal platforms to reach the targeted audiences were Twitter and Facebook. After Steering Committee approval, the DCC formed an internal Social Media Team to develop the Network’s social media policy, develop content, and launch the accounts. The Network’s Twitter (@BMTCTN) (Figure 3.3) and Facebook (facebook.com/bmtctn) (Figure 3.4) accounts were launched in October 2014. The BMT CTN now has 1,132 Twitter followers and 184 Facebook “likes”, which is an increase of 525 and 42, respectively. The

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 3.0 Administrative Functions of the DCC greatest activity continues to be during the annual ASH and BMT Tandem Meetings. Many new Twitter followers and Facebook likes were gained during these meetings, and it proved to be an effective way of promoting BMT CTN activities and presentations during the meetings. Figure 3.3. Screen shot of BMT CTN Twitter account

Figure 3.4. Screen shot of BMT CTN Facebook account

The DCC Social Media Team set monthly target metrics for both accounts in April 2015 based on the Network’s account activity. During this reporting period, the DCC Leadership Team requested the metrics be compared to similar organizations to determine if they were reasonable. In March 2017, the Social Media Team sent a survey to similar consortia and organizations to assess their social media usage. The survey evaluates which accounts these groups are using, their activity level, the successfulness and usefulness of their accounts, the benefits and disadvantages of each, the amount of time spent on social media efforts, and their target metrics. The survey results will be available in the next reporting period. Based on these results and re-evaluation of the metrics, the DCC Social Media Team will make recommendations to the DCC leadership regarding future strategies for the accounts. 3.6 Training Ongoing education is imperative for ensuring protocol compliance and data quality. DCC staff members conduct site visits and calls to transplant centers to initiate protocols and educate center personnel on Network policies and procedures. Research staff members at the center receive an initiation report. Clinical Research Associate training sessions are held annually in conjunction with the BMT Tandem Meetings. These sessions cover data entry, quality control issues, and reviews of procedures and protocol requirements. They also provide the DCC with useful feedback from centers. General Clinical Research Associate calls and protocol-specific calls are held as necessary, with minutes distributed to research staff. Additionally, the Network

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 3.0 Administrative Functions of the DCC provides online training in its AdvantageEDC and GlobalTrace software packages that includes training modules with a training practicum (AdvantageEDC) and competency assessments (GlobalTrace). The Network also prepares an electronic newsletter for research staff and provides a variety of materials to assist centers in understanding and implementing protocol requirements. 3.7 Transplant Center Monitoring The DCC regularly monitors the performance of BMT CTN Core Centers and their contributions to the Network. Daily or monthly accrual reports, form delinquency, number of data queries, and major and minor protocol violations are tracked. The Data and Safety Monitoring Board routinely reviews these data. Center Performance Reports (Attachment C1) are prepared annually (most recently in January 2017). Overall scores on Center Performance Rating (Attachment C2) are based on five categories:  Scientific / administrative contributions (10 points);  Patient accrual (60 points);  Activation and enrollment (10 points);  Data quality (10 points);  Laboratory compliance (10 points). Final scoring is a composite of category-specific metrics associated with each of these measures of commitment and involvement. Centers that receive a “needs improvement” score in any area must submit an action plan for resolving problems within six weeks of receiving the report. Additionally, Center Performance “snapshots” of actual-versus-projected accrual and laboratory compliance reports are distributed to Core Centers quarterly. During this reporting period, the DCC reviewed center performance data for the current grant cycle (2012- 2016; reports were not issued for 2011 as the grant cycle started mid-year). As shown in Figure 3.5, the number of centers with an overall score of “Needs Improvement” increased from zero to five. This is primarily attributable to lower accrual; three larger studies closed during the year, and three others were not activated until the end of the year. Data by Core Center / Consortium are provided in Table 3.2. Figure 3.5. Overall assessment of Core Center performance by year 100%

90%

80%

70%

60% Outstanding 50% Acceptable 40% Needs Improvement 30%

20%

10%

0% 2008 2009 2010 2012 2013 2014 2015 2016

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 3.0 Administrative Functions of the DCC

Table 3.2. Core Center / Consortium-specific assessment of center performance Overall Center Performance by Core Center / Consortium

2012 2013 2014 2015 2016 Center Name Score Assessment Score Assessment Score Assessment Score Assessment Score Assessment Baylor College of Medicine Consortium1 25.0 Needs Imp 40.0 Needs Imp 85.9 Acceptable 100 Outstanding 45.0 Needs Imp Case Western Reserve Univ Consortium 77.4 Acceptable 79.2 Acceptable 79.4 Acceptable 86.1 Acceptable 79.9 Acceptable City of Hope National Medical Center 88.8 Acceptable 60.3 Acceptable 84.6 Acceptable 67.7 Acceptable 69.4 Acceptable Dana Farber Consortium 86.0 Acceptable 68.8 Acceptable 89.2 Acceptable 89.4 Acceptable 93.4 Outstanding Duke University Medical Center 33.8 Needs Imp 81.9 Acceptable 79.3 Acceptable 70.8 Acceptable 85.0 Acceptable Fred Hutchinson Cancer Research 91.3 Outstanding 86.8 Acceptable 88.5 Acceptable 86.4 Acceptable 73.3 Acceptable H.Center Lee Moffitt Cancer Center 86.3 Acceptable 77.5 Acceptable 92.0 Outstanding 81.6 Acceptable 64.9 Acceptable Johns Hopkins University 36.9 Needs Imp 81.0 Acceptable 72.1 Acceptable 90.0 Outstanding 90.0 Outstanding Memorial Sloan-Kettering Cancer Center 85.6 Acceptable 78.2 Acceptable 85.9 Acceptable 85.0 Acceptable 56.8 Needs Imp Northside Hospital Atlanta 76.9 Acceptable 91.1 Outstanding 93.5 Outstanding 87.9 Acceptable 93.8 Outstanding Ohio State University Consortium 70.1 Acceptable 85.0 Acceptable 89.6 Acceptable 94.5 Outstanding 94.3 Outstanding C PBMTC 31.5 Needs Imp 38.3 Needs Imp 83.6 Acceptable 89.3 Acceptable 43.8 Needs Imp Stanford Hospital and Clinics 42.0 Needs Imp 93.2 Outstanding 94.5 Outstanding 89.3 Acceptable 87.7 Acceptable University of Florida Consortium 89.7 Acceptable 83.0 Acceptable 86.0 Acceptable 85.3 Acceptable 84.4 Acceptable University of Michigan Consortium2 73.7 Acceptable 91.9 Outstanding 87.5 Acceptable 94.4 Outstanding 87.4 Acceptable University of Minnesota 91.8 Outstanding 60.8 Acceptable 34.1 Needs Imp 89.3 Acceptable 65.9 Acceptable University of Nebraska Consortium 77.0 Acceptable 83.6 Acceptable 78.0 Acceptable 80.2 Acceptable 81.2 Acceptable University of Pennsylvania Hospital 34.0 Needs Imp 25.7 Needs Imp 84.5 Acceptable 79.3 Acceptable 72.1 Acceptable University of Texas MD Anderson 53.5 Needs Imp 50.6 Needs Imp 94.4 Outstanding 90.6 Outstanding 38.4 Needs Imp Washington University 83.0 Acceptable 27.0 Needs Imp 84.5 OutstandingAcceptable 79.9 Acceptable 34.2 Needs Imp S Notes: 1 Children’s National Medical Center joined the Baylor College of Medicine Consortium in January 2014, soAcceptable the 2012 and 2013 assessments of the consortium only measured the Baylor College of Medicine. 2 Mayo Clinic joined the University of Michigan Consortium in January 2013, so the 2012 assessment of the consortium only measured the University of Michigan. Abbreviations: Needs Imp – Needs Improvement

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 3.0 Administrative Functions of the DCC

3.8 Specimen Repository Support 3.8.1 Specimen Collection Each BMT CTN protocol creates an important new opportunity for the scientific community to collect baseline and post-transplant / post-treatment biologic specimens for clinical research. For most protocols, biologic samples are collected for use in protocol-defined research aimed at answering specific questions for that patient population and its transplantation outcomes. Collection of supplementary samples is incorporated into most protocols for use in future research. These samples and the associated clinical data are made available as a valuable resource for investigators at large. BMT CTN research sample inventories continue to be regularly updated on the Network’s public website to help investigators better utilize this resource. This section provides important information regarding the procedures associated with biospecimen requests, the study proposal approval process, and biospecimen summaries listing available samples for all studies by time point and sample type. Network public website links are also provided to guide investigators to older BMT CTN trial biospecimen and clinical data collections that are now being maintained and made available as public collections by NHLBI Biorepository and BioLINCC. The DCC receives requests for the use of its research samples for transplantation or post-transplantation treatment-related ancillary studies. The procedures for judging the scientific merit of such studies, including evaluations by the parent study Protocol Team, Biomarkers Committee, DCC, and Steering Committee, are defined in the Administrative Manual of Procedures. As of March 31, 2017, a total of 390,021 available research specimens, provided by 6,165 subjects, were stored by the BMT CTN Repository Network: NHLBI Repository, BMT CTN Sample Repository operated by NMDP/Be The Match, and the AIDS and Cancer Specimen Resource Repository. A summary of currently available research samples at the NHLBI Repository, BMT CTN Sample Repository, and AIDS and Cancer Specimen Resource Repository is displayed in Tables 3.3a, 3.3b, and 3.3c, respectively. Table 3.3a. BMT CTN center processed samples available at the NHLBI Repository BMT CTN Currently Available Subjects with Available Protocol Biospecimens Biospecimens NHLBI Managed Open Collection NHLBI Managed Open Collection (only clinical data) (only clinical data) 0101 The biospecimens initially stored have been shipped to protocol- defined and ancillary project laboratories. NHLBI Managed Open Collection NHLBI Managed Open Collection (biospecimens and clinical data) 0102 (biospecimens and clinical data) 613 patients 10,482 85 donors NHLBI Managed Open Collection NHLBI Managed Open Collection 0201 (biospecimens and clinical data) (biospecimens and clinical data) 6,940 436 patients NHLBI Managed Open Collection NHLBI Managed Open Collection (biospecimens and clinical data) 0402 (biospecimens and clinical data) 280 patients 16,244 184 donors

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 3.0 Administrative Functions of the DCC

Table 3.3b. Samples processed and available at the BMT CTN Sample Repository BMT CTN Currently Available Subjects with Available Protocol Biospecimens Biospecimens 0302 881 137 patients 0401 219 115 patients 0701 95 57 patients 0702 42,334 672 patients 07LT 2,152 176 patients 0801 4,119 144 patients 0802 5,816 205 patients 0901 1,190 241 patients 261 patients 1101 14,559 96 donors 1102 4,310 194 patients 1202 260,661 1,710 patients 1203 10,897 242 patients 1204 3,295 33 patients 1301 3,020 160 patients 1302 718 29 patients 1401 431 34 patients 1501 795 19 patients

Table 3.3c. Samples processed and available at the AIDS and Cancer Specimen Resource Repository BMT CTN Currently Available Subjects with Available Protocol Biospecimens Biospecimens 0803 737 35 patients 0903 126 7 patients

During this reporting period, 150 frozen sample aliquots were shipped from the BMT CTN / NHLBI repositories to project laboratories for the following protocol-defined and ancillary correlative studies. Letters of BMT CTN support for several additional BMT-related studies were provided to investigators for their grant applications. Final biospecimen qualification, selection, and sample shipping will follow upon successful receipt of awarded study funding.  BMT CTN 0702: 150 samples – Evaluate the relationship of obesity, cytokines, and disease status in patients undergoing HCT for multiple myeloma

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 3.0 Administrative Functions of the DCC 3.8.2 Research Sample Repository and Central Processing Lab The central processing laboratory at the BMT CTN Research Sample Repository plays an important role in standardizing complex specimen processing procedures and expanding the collection of quality sample types for correlative studies. The availability of these services, which will be applicable to many future studies, helps reduce the research sample processing burden for clinical sites. The BMT CTN processing laboratory received and processed samples from more than 1,680 Network shipments during this reporting period, with recent monthly averages of more than 130 shipments. The laboratory is currently processing peripheral blood samples into serum, plasma, PAXgene blood RNA and DNA lysates, viable peripheral blood mononuclear cell (PBMC), granulocyte, and buffy coat sample types. Bone marrow aspirates, buccal swabs, and viable marrow product mononuclear cell sample types are also being processed and stored at the BMT CTN Research Sample Repository. Over the past three reporting periods, there was a significant need throughout the Network to provide clinical sites with a way to collect research biospecimens on a Friday when their patients are seen by transplant center care providers. Previously, if samples were collected on Fridays, they would have been:  Missed;  Collected outside of the target collection window (if study permitted);  Collected, held over the weekend and shipped on Monday, thereby decreasing the quality of sample and often becoming unusable for many purposes;  Processed and frozen by the clinical site, if they were willing to do so and sample type would allow. In response to this need and requests from several BMT CTN clinical sites, the NMDP/Be The Match and BMT CTN responded by extending the hours of staffing and sample processing and biospecimen storage to now include Saturdays. This solution, implemented in February 2015, is consistently demonstrating a positive impact on compliance and increased partnership in this BMT CTN network-wide research-related initiative. In this reporting period, the BMT CTN Biorepository received and processed samples on Saturdays from 165 shipments, which were associated with 6 different BMT CTN clinical trials. 3.8.3 Maximizing Sample Collection, Quality, and Availability The DCC continues to invest substantial efforts to improve Network procedures for research sample collection, associated data accuracy, sample storage, and research sample testing. Highlights of these efforts and benefits include:  Promoting the use of stored biospecimens and associated clinical trial data for ancillary laboratory research studies. The DCC obtained BMT CTN Steering Committee support and released a request for applications (RFA) for laboratory study proposals from investigators who wished to address supplemental questions that develop from the Network’s portfolio of prospective clinical trials and available research biospecimens. Five proposals were received and evaluated for scientific merit, perceived impact, feasibility of completion within the desired project time frame, and scope of the requested budget. Four of the five laboratory studies were approved and awarded in early 2015, resulting in an investment of approximately $355,000. During this reporting period, DCC staff members worked with investigators to ensure study testing was completed and provide any additional clinical trial data needed for the final analysis of biomarker testing results in the context of the various transplant outcomes being studied. To date, two study reports were presented at international meetings (ASH Annual Meeting and BMT Tandem Meetings); one manuscript was published, and another was recently submitted. All other studies are either nearing completion, or investigators are actively completing manuscripts or brief reports of their findings for submission to peer-reviewed journals.

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 3.0 Administrative Functions of the DCC

 Continued integration of standardized sample acquisition forms and sample tracking (AdvantageEDC and GlobalTrace). Systematic sample data collection and specimen tracking provides additional real- time center assessment opportunities to increase the accuracy and compliance of sample collection information at each critical time point. The availability of sample acquisition forms in the AdvantageEDC forms grid provides centers an additional reminder of future sample collection target dates, facilitating patient appointment scheduling.  Continued development of a network of research and clinical laboratories that support current and future studies. Since inception, the BMT CTN has partnered with more than 25 academic and commercial laboratories and clinical consultants to support the growing correlative research portfolio of the Network. Announcements of future laboratory support opportunities are communicated on the BMT CTN public website and via email to current and past Core and Affiliate Center Principal Investigators at pre-screened clinical and research laboratories. Additionally, the ASBMT and the American Society for Clinical Pharmacology and Therapeutics send notification emails to their members regarding Request for Proposal opportunities for laboratory support of BMT CTN ancillary studies.  Continued review of all pending sample shipments to the NHLBI Repository for older protocols. This process continues to provide an opportunity to review key procedures with center staff and to discuss effective sample management strategies, build relationships with research staff, and receive feedback on transplant center needs. The DCC continues to work with Network Centers and NHLBI BioLINCC staff to proactively review sample manifest inventory data to ensure accurate linkage of clinical data associated with research samples being submitted for inclusion in BMT CTN biospecimen collections.  Review of comprehensive center-specific sample collection and required laboratory testing compliance reports. Clinical centers receive the information they need to assess their achievements and areas of deficiencies and to facilitate discussions with DCC staff. These reports are periodically reviewed by DCC staff members who contact centers to discuss opportunities for improvement and process optimization. DCC staff members currently receive an average of about 50 inquiries per week from clinical sites regarding guidance concerning upcoming research sample collection requirements, related procedures, and patient scheduling alternatives. The productive center relationships that have been built over the years have resulted in a high level of trust and confidence in the DCC, both in terms of their leadership and their abilities to manage and provide guidance on difficult situations encountered at centers.  Focus on more complete instructional materials, training, and educational opportunities for research staff. Education efforts have improved understanding of the purpose and importance of the research sample collections by transplant center staff. Staff members are encouraged to discuss and develop best practices for tracking upcoming research sample collections and improving accuracy of patient information associated with biologic research samples. Dedicated DCC personnel and Research Sample Repository staff are always available to answer questions and support transplant center staff. DCC staff members also provided multiple roundtable discussions during the 2017 BMT Tandem Meetings. One such discussion included the opportunity to review and discuss procedures and best practices associated with research sample collections in support of several key BMT CTN clinical trials.

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 4.0 Concept to Publication: The Protocol Process 4.0 Concept to Publication: The Protocol Process

Since its establishment in 2001, the Network has refined its processes for supporting selection, development, and implementation of studies. Current procedures reflect the Network’s commitment to efficient use of its resources to implement well-designed studies that accrue sufficient numbers of patients as rapidly as possible. This section describes the typical sequence of events. There is substantial overlap in the timeframes of these steps, as the Network seeks to implement tasks in parallel rather than sequentially whenever possible. Transplant center investigators, Protocol Team members, DCC staff members, external oversight bodies (Protocol Review Committee and Data and Safety Monitoring Board), NCI National Clinical Trials Network Group collaborators, and funding partners (NHLBI and NCI) are all involved in developing, implementing, and completing studies. The Steering Committee is responsible for:  Reviewing and prioritizing all concepts proposed for Network consideration;  Approving final draft protocols prior to Protocol Review Committee and Data and Safety Monitoring Board review;  Overseeing execution and analysis of approved Network trials. Figure 4.1 displays the protocol development and implementation processes described in this section. Figure 4.1. Schema for protocol development and implementation Protocol Development Protocol Approval Concept Protocol Proposal Evaluation / Steering PRC DSMB IRBs Development Approval Committee Technical Committees

Protocol Implementation / Completion

Activation Maintenance Closure Case Report Forms* / Study Accrual / Compliance / Data review / Data documents and procedures* / Data Data quality / Safety / files / Analysis / systems* / Contracts / Accrual plan* / Amendments / Abstracts / Educational materials* / Site training Continued site training Publications

* Work on these documents / tasks begins during the protocol development phase and is generally close to completed by the time the first IRB approvals are available. 4.1 Concept Evaluation and Approval Any investigator may submit study concepts for consideration. Study proposal requirements are posted on the Network’s public website (https://web.emmes.com/study/bmt2/Newstudyform.html). 4.1.1 DCC Review Study concepts are submitted first to the DCC, which performs a preliminary review to ensure the proposed study does not conflict with an active study and the proposal is complete. The DCC then distributes the study concept to the Executive Committee for discussion at a regularly scheduled monthly meeting.

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 4.0 Concept to Publication: The Protocol Process 4.1.2 Executive Committee Review The Executive Committee reviews the study concept to ensure that it is consistent with the Network’s mission, does not compete with active BMT CTN protocols or BMT CTN protocols in development, and poses no major conflicts of interest. Eligible proposals are scheduled for review by the Steering Committee. 4.1.3 Steering Committee Review Study concepts are scheduled for discussion at the monthly Steering Committee conference calls or in person meetings, which are held three times per year. The Steering Committee evaluates concepts for scientific merit, feasibility, and Network members’ willingness to participate. The Steering Committee may accept, reject, or recommend changes to the study concept. The DCC assists in the review process, using CIBMTR data to assess feasibility based on study population and eligibility requirements. The DCC supports the Steering Committee in its deliberations by providing the following information whenever possible:  Numbers of patients currently undergoing transplantation at Core and Affiliate Centers who might meet eligibility criteria;  Outcomes of interest in the specified population;  Evaluation of sample size requirements;  Suggestions for alternate study designs;  Special requirements for research samples and/or necessary agents;  Potential competing protocols. 4.2 Protocol Development 4.2.1 Establishment of a Protocol Team When the Steering Committee approves a study concept, the DCC assigns it a protocol number, and a Protocol Team is formed. The Protocol Team meets weekly by teleconference during the development process and may hold in-person meetings to expedite the development of the protocol. The Steering Committee reviews team progress as needed. The Protocol Team includes:  Protocol Chairs (Study Principal Investigators). The Protocol Chairs, generally the investigators who submitted the original concept, have primary responsibility for the protocol’s development and progress. Most Network protocols have two or three Chairs.  Core and Affiliate Centers Representatives. Most Protocol Teams have four to six representatives (co- investigators) from Core and Affiliate centers.  Protocol Officer. The Protocol Officer is a physician DCC member who helps address scientific and medical issues.  Protocol Coordinator. A DCC Protocol Coordinator manages logistical and practical issues, such as coordinating meetings, preparing minutes, and maintaining protocol version control.  Protocol Statisticians. DCC and NHLBI statisticians create and coordinate the Statistical Analysis Plan (Section 4.2.2).  Contracts Representative. A DCC Contracts Representative manages Core and Affiliate Clinical Trials Agreements as well as laboratory, central pharmacy, supply procurement, and contributor agreements. 4.2.2 Statistical Design Statistical analyses of study data are prepared and documented either in a Statistical Analysis Plan within the protocol document or as a standalone plan. This plan includes a synopsis of the study design; endpoints;

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 4.0 Concept to Publication: The Protocol Process hypotheses; randomization and stratification procedures; sample size and power calculations; stopping rules for efficacy, futility, and/or toxicity; planned analyses of primary and secondary endpoints; adjustment for multiple testing; and control of type I error and subgroup analyses. Since the potential pool of patients for HCT trials is limited, statistical designs must make optimal use of available patients. Additionally, HCT trials face some unique challenges:  When donors and recipients are consented and randomized separately, delays in this process can lead to dropout, as seen in BMT CTN 0201.  There is the potential for multiple complications (infection, organ toxicity, GVHD, relapse, etc.) during the early post-transplantation period. Therefore, competing risks must be considered with all study endpoints. Competing risks are commonly addressed using composite endpoints as the primary outcome measure, as in BMT CTN 0101, 0402, 1203, and 1301. The CIBMTR Research Database helps identify patient candidates for study exclusion due to high risks of competing events. Cumulative incidence estimators are used to approximate probabilities of individual events occurring in the presence of competing risks.  Non-proportional hazards and crossing survival curves occur when treatments under investigation have different timing of events, as with allogeneic versus autologous HCT (BMT CTN 0102), different regimen intensities (BMT CTN 0901), or different graft sources / donor types (BMT CTN 1101). If this occurs, the usual log-rank test is inappropriate, and a pointwise comparison of survival probabilities is often performed instead. CIBMTR data are again useful in identifying an appropriate follow-up time point, a time when most events of interest have occurred. More efficient methods for comparing groups with non-proportional hazards were recently implemented for the analysis of BMT CTN 0901.  Analysis of quality-of-life data must consider non-ignorable missing data due to early mortality, particularly when quality of life is the primary endpoint, as in BMT CTN 0902.  Primary and key secondary endpoints may be closely related, and explicit control of the familywise Type I Error rate is required, as seen with the gatekeeping procedures implemented in BMT CTN 1301.  Selection of a clinically meaningful primary endpoint is extremely important in determining the size and interpretability of a clinical trial. This selection must carefully balance the time required to observe clinically meaningful differences (e.g. overall survival may require years of follow-up) versus the need to complete trials and report results to the scientific community in a reasonable timeframe. BMT CTN statisticians have extensive experience in navigating this balance while maintaining interpretability as shown in the upcoming BMT CTN 1506 study, which included extensive consultations with the FDA regarding the benefits and risks of relapse-free survival as the primary endpoint for a Phase III trial. Emmes and CIBMTR statisticians are experts in analysis of HCT data, with many methodological publications to their credit. This expertise is an invaluable resource for addressing statistical challenges. DCC statisticians hold regular conference calls as well as ad hoc calls with PhD and Master’s-level statisticians to discuss current analyses and approaches to statistical issues. These discussions help ensure consistent, high quality, and appropriate statistical analyses for BMT CTN studies. 4.2.3 Accrual Planning Accrual planning is an important step in the protocol development process. The BMT CTN Project Manager works with Protocol Team members to develop a customized accrual plan for each study. The accrual plan for each study considers projected accrual rates from Core and Affiliate Centers, data on potentially eligible patients from the CIBMTR Research Database, potential accrual barriers and competing studies, a list of advocacy and

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 4.0 Concept to Publication: The Protocol Process other groups that should receive information about the trial, materials to be developed for referring physicians and study participants, and target meetings and audiences for presentations and educational sessions. When eligibility criteria are established, the Protocol Coordinator invites Core Centers to participate. The invitation survey also asks investigators to provide projected accrual, input into the study design (e.g. potential accrual barriers), and primary study contacts. Using the CIBMTR Research Database, accrual projections are compared to each center’s reported activity, and discrepancies are resolved. Often there are not enough potentially eligible patients from participating Core Centers, so the DCC reaches out to Affiliate Centers that have both the potential for contributing substantively to accrual and the necessary expertise to execute the study. During review of the accrual plan, the protocol team assesses anticipated accrual barriers and considers ways to minimize the barriers. The team also determines if any additional study materials need to be developed, e.g. for patients or referring physicians. Informational and educational materials are particularly important for studies involving patient populations that are not usual HCT candidates or that involve complex research activities. For example:  The Protocol Chairs for two sickle cell disease protocols (1503 and 1507) sent study synopses and letters to hematologists responsible for treating sickle cell disease patients. These materials informed the hematologists of the studies and requested their participation in referring potential patients to their local transplant center.  The 0801 team developed a video to demonstrate the chronic GVHD assessments required by the protocol.  The 1101 team published an article to promote the study, which included follow-up data from the Phase II 0603/0604 precursor studies and a donor selection algorithm flow chart. Protocol teams assess whether informational or educational sessions should be held to promote the study and the target audiences for these sessions. Educational sessions are also planned during the annual BMT Tandem Meetings at the BMT CTN Coordinators or Investigators Meetings, as a component of the scientific sessions, or as standalone investigator meetings. Other educational sessions have included grand round presentations at participating centers by Protocol Chairs and webinars for transplant center investigators and coordinators. The accrual plan is approved by the protocol team prior to release of the protocol. It is re-evaluated throughout the course of the study, as needed, e.g. if unanticipated accrual barriers occur, accrual is slower than anticipated, or opportunities for additional educational opportunities are identified. See Section 4.6.1 for more information about accrual monitoring and intervention. 4.2.4 Budget Preparation When a draft protocol is available, the NMDP/Be The Match Finance Department arranges a teleconference with the Protocol Chair(s), Officer, and Coordinator as well as other key parties to initiate budget preparation. The Finance Department drafts a budget based on the final draft protocol as well as laboratory and services requirements. Costs of labor for center and DCC personnel, medications, other therapies, shipping, and supplies are also considered. The Protocol Chair(s) and Protocol Officer review the draft budget, which is included in the materials that are distributed to the Protocol Review Committee. Before submission to NHLBI and NCI for approval, the NMDP/Be The Match Chief Financial Officer (or appropriate designee, such as the Chief Medical Officer), Steering Committee Chair, and DCC Principal Investigator review and sign the final draft budget.

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 4.0 Concept to Publication: The Protocol Process 4.2.5 Federal Regulations The DCC maintains protocol-specific regulatory files for the Network, including investigator agreements or FDA 1572 forms, investigator curriculum vitae, IRB approvals and approved consent forms, delegation of authority logs, financial disclosures, medical licenses, pharmacy licenses (if applicable), and evidence of Human Subjects Research Training staff certification for each Core and Affiliate Center. The DCC prepared and submitted four Investigational Device Exemption applications, which were required for BMT CTN protocols 0101, 0303, 0801, and 1301. The DCC also submitted 12 Investigational New Drug applications to the FDA for BMT CTN protocols 0102, 0201, 0302 / 0403, 0401, 0701, 0702 / 07LT, 0801, 1101, 1203, 1302, 1401, and 1501. The FDA subsequently deemed Investigational New Drug / Investigational Device Exemption applications unnecessary for BMT CTN protocols 0101, 0701, 0801, 1101, and 1501. 4.2.6 Final Draft Protocol The development process results in a final draft protocol document that provides the necessary details to perform a clinical trial. This document includes:  An outline of the study design;  Study background, scientific rationale, and objectives;  Detailed description of treatments;  Detailed description of experimental design, including the Statistical Analysis Plan;  Definition of primary and secondary endpoints;  Eligibility requirements;  Follow-up schedules and requirements for patient exams;  Specimen submission schedules;  Safety measurements and adverse event reporting procedures;  Registration and randomization procedures;  Procedures for blinding study treatments;  Protocol-specific technical guidelines (e.g., donor selection criteria and graft processing techniques);  Informed consent template(s);  References;  Appendices. The final draft protocol then undergoes a multi-step review process, as follows. 4.3 Protocol Approval The final draft protocol requires approval by the Steering Committee, BMT CTN Technical Committees, the Protocol Review Committee, the Data and Safety Monitoring Board, and applicable IRBs. 4.3.1 Steering Committee Review Two weeks in advance of Steering Committee review of a final draft protocol, the Steering Committee Chair assigns two or three members as primary reviewers. These reviewers study the final draft protocol in detail. They complete a BMT CTN Reviewer Checklist and evaluate the study’s background and rationale, design, endpoints, clinical and laboratory tests, statistical considerations, informed consent, and ancillary studies. They also provide an overall assessment of the protocol. The final draft of the protocol is then presented at a Steering Committee meeting.

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 4.0 Concept to Publication: The Protocol Process

If approved by the Steering Committee, a Protocol Review Committee presentation is scheduled. Simultaneously, the final draft protocol is distributed to the five Technical Committees responsible for final draft protocol review. 4.3.2 Protocol Review Committee The Protocol Review Committee assessment is scheduled through NHLBI. This group performs scientific review of each study. Several weeks in advance of each scheduled meeting, the DCC submits review materials, listed below, to the Protocol Review Committee:  Final draft protocol and informed consent(s);  Frequently Asked Questions document;  Accrual plan;  Reviewer Checklist. The Protocol Review Committee conducts a preliminary evaluation of the documents and returns the checklist to the Protocol Team with comments regarding the study objectives, design, feasibility, statistical approach, study operations, and human subjects protection. The Protocol Team sends its written responses back to the Protocol Review Committee prior to the scheduled presentation. This approach makes deliberations more efficient and usually avoids the need for follow-up meetings and potential delays in implementation of the protocol. Once it receives Protocol Review Committee approval, the protocol is scheduled for Data and Safety Monitoring Board review. 4.3.3 Data and Safety Monitoring Board Review Each BMT CTN trial is approved and monitored by one of two NHLBI-appointed Data and Safety Monitoring Boards. Boards have scheduled Webcasts in March, May, October, and December as well as in-person meetings in April and November to review the safety and efficacy endpoints outlined in the statistical sections of each protocol being presented. The DCC is responsible for providing the Boards with the information necessary for them to make their determinations. The Data and Safety Monitoring Boards must approve all new protocols or protocol amendments before implementation. When protocols or amendments are scheduled for review, the Data and Safety Monitoring Board provides written comments to the Protocol Team for response prior to the Data and Safety Monitoring Board meeting, similar to the Protocol Review Committee process. The BMT CTN’s Data Safety Monitoring Plan was reviewed by the Data and Safety Monitoring Boards and approved by NHLBI. All clinical sites enrolling patients on BMT CTN trials must adhere to the reporting requirements in the approved Data Safety Monitoring Plan. The DCC prepares all materials for Data and Safety Monitoring Board meetings and posts them for the Board on a password-protected website (bmtctnsp.net). The DCC also posts monthly safety monitoring reports, including adverse event reports and stopping guideline safety tables and graphs. These reports, in addition to accrual, monthly recruitment data quality, and site activation status reports, are available to the Data and Safety Monitoring Board members and to NIH program staff. After all Data and Safety Monitoring Board reviews, the DCC disseminates the Board’s recommendations (after approval by NHLBI) to the Protocol Chairs; Protocol Officer; additional protocol team members; and select DCC staff members. The DCC also distributes a summary of recommendations to Investigators, Coordinators, and other key personnel at the participating centers for relay of the information to their local IRBs. These memos are also posted on the appropriate protocol-specific pages of the Network password-protected website (bmtctnsp.net). The DCC ensures center compliance with the recommendations, including center IRB review and

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 4.0 Concept to Publication: The Protocol Process approval, training, accrual closure, and additional data review, as needed. 4.3.4 Final Review Prior to Release to Centers After the Data and Safety Monitoring Board approves the protocol, the two Protocol Chairs and the Protocol Officer review the protocol a final time, using a review checklist. Starting in 2011, a final sign-off process was implemented. After the review is complete, at least two of the three reviewers must sign the first page of the protocol before it is distributed to centers. 4.4 Protocol Pre-Activation To expedite study implementation and facilitate timely activation and successful accrual, the following activities occur concomitantly with protocol development:  Creating Case Report Forms;  Preparing and distributing other protocol-specific materials, including a Laboratory Research Sample Information Guide, Data Management Manual and Forms Guide, and guides for pharmacy procedures, if applicable;  Modifying data systems to receive and monitor protocol-specific data;  Developing systems to acquire, store, distribute, and analyze protocol-specific biospecimens;  Contracting with centers, laboratories, pharmacies, and contributors. The Protocol Team also forms an Endpoint Review Committee, with a charter, before the study opens to accrual. The Protocol Coordinator and Statistician are responsible for preparing review materials for the Endpoint Review Committee. These materials:  Outline the primary and secondary endpoints to be evaluated;  Identify the endpoints to be adjudicated and the process for adjudication;  Define procedures for resolving discrepancies and recording results;  Outline the mechanisms for assessing subject eligibility and protocol compliance;  Conduct final reviews of the study data in a blinded manner whenever possible. 4.4.1 Designing Case Report Forms Designing data collection forms is a collaborative venture involving each study’s scientific and clinical leadership, statisticians, laboratory collaborators, and the DCC. Standard processes ensure the study will have clear, easy-to-use forms that provide data to support its objectives without overwhelming study resources. The DCC is responsible for developing Case Report Forms and, to date, has developed 19 core Case Report Forms for use in all protocols. Another 424 protocol-specific forms were developed, and 43% are currently in use. Protocol-specific forms capture data on particular endpoints, important covariates, protocol-specified treatments, severe adverse events, and protocol compliance. Draft forms are distributed to the Protocol Team for review and input, and the revised forms are then reviewed by the Clinical Research Associates Committee, which evaluates them from a practical use perspective. Significant data elements are explicitly defined in a User’s Guide or via “help text” in the system to minimize variability in responses. DCC staff members test each form prior to release. 4.4.2 Educational Materials and Other Study Documents The NMDP/Be The Match’s Patient and Health Professional Services Department works with the Network to develop patient education materials to support new clinical trials. These materials help educate potential patients about the basics of clinical trials and provide a patient-friendly summary of the specific clinical trial. Educational materials are created for each new study and are available with the protocol when it is released for initial IRB 53

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 4.0 Concept to Publication: The Protocol Process submission. Patient and Health Professional Services staff members also help design informed consent documents so that they are patient-friendly and written at an eighth-grade reading level. The Network is evaluating a new two-column template for informed consent documents via the randomized Easy-to-Read Informed Consent study (BMT CTN 1205), for which accrual was completed during this reporting period. The full analysis and protocol team recommendations for future consent form format will be presented to the Steering Committee in May 2017. 4.4.3 Release to Center IRBs Once the protocol is approved by the Data and Safety Monitoring Board, the DCC releases the protocol materials to centers that agreed to participate so that they can submit the materials to their local IRBs. Each protocol includes a template for documenting Informed Consent that can be modified by participating centers to meet their local IRB requirements. In 2016, the DCC instituted an optional single IRB approach for BMT CTN 1501 and 1503. The NMDP IRB agreed to serve as the IRB of Record for this pilot project. To date, approximately 30% of participating centers selected the NMDP IRB as their IRB of record for these two studies. NHLBI leadership approved this plan and encourages centers to participate. The NMDP IRB is accredited by the Association for the Accreditation of Human Research Protection Programs and was audited by the FDA in 2006 and 2015, both times with no findings. The NMDP IRB assumed responsibility for the studies on behalf of institutions that agreed. Each institution completed an IRB Authorization Agreement and a local context questionnaire to delegate responsibility to the NMDP IRB. At the start of the new grant cycle on July 1, 2017, the NMDP IRB will serve as the single IRB for all new BMT CTN protocols. Centers will be required to use the NMDP IRB at that point in time. 4.4.4 Site Initiation Training Prior to protocol implementation, the Protocol Coordinator arranges multiple site initial web conferences with key center personnel to review materials and processes. A Protocol Chair or Officer also participates in the call. The purpose of the training is to make certain the responsibilities and communication lines within each center are clear. Study procedures are discussed, including procedures for data and sample collection. If local pharmacies or laboratories are involved in a study, representatives from those departments participate in the site initiation web conferences as well. A site initiation report is issued to all site personnel involved in the protocol within 60 days. The Network’s Sample Repository Research Administrator plays an important role in preparing centers for their biospecimen submissions by:  Creating a protocol-specific Research Sample Information Guide;  Providing telephone and email support for site-specific questions regarding the IRB, project laboratories, repositories, or information in the Research Sample Information Guide;  Providing training and ongoing technical and contractual support for all project laboratory staff on the protocol. Customized initiation training is provided when needed. For example:  BMT CTN 1101 has cord blood training requirements that differ from other trials, requiring additional training calls for clinical centers activating this trial.  BMT CTN 1301 is under an investigational device exemption (IDE) involving the CliniMACS® CD34 Reagent System to perform a cell selection procedure, which is not commonly performed on other trials. Training in the operation of the device is provided to center’s stem cell laboratory personnel by Miltenyi

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 4.0 Concept to Publication: The Protocol Process

Biotec. The CliniMACS® CD34+ Cell Selection Procedure Standard Operating Procedure (BMT-1301- 01.01 v2.0) was created specifically for this study to ensure centers follow a similar approach across multiple centers. The standard operating procedure requires sign off by the Stem Cell Laboratory Director at each center to acknowledge that they have reviewed and understand the procedure. To help ensure quality and consistency of processed products across multiple centers, stem cell laboratory personnel of each center are required to attend a Laboratory Coordinator training, via web conference.  BMT CTN 1401 is a unique study that involves not only a clinical component but also a cell therapy component. Sites are manufacturing patient specific vaccine in their own good manufacturing practice- compliant cell processing facilities. This process involves cell collection, sterile culture, and storage of myeloma tumor cells. These selected sites have undergone hands-on training at the 1401 central laboratory at Beth Israel Deaconess Medical Center in Boston, MA. Furthermore, these sites are also required to generate successful mock runs of vaccine generation at their own facility and send aliquots to Beth Israel Deaconess Medical Center to test whether the vaccine meets the specified release criteria prior to site activation. Because of the complexity of the training and regulatory oversight, there are a limited number of sites allowed to participate in the 1401 trial. 4.4.5 Medical Monitor Assignment The DCC assigns a Medical Monitor to each study when it is activated. Medical Monitors are transplant physicians familiar with the conduct of clinical research and regulatory requirements for safety monitoring and reporting. When applicable, Medical Monitors with disease-specific expertise are also recruited to monitor the study (e.g. sickle cell disease, HIV). The Network’s Medical Monitors hold teleconferences quarterly to ensure uniformity in assessing adverse events and to share updates on regulatory requirements. As a matter of policy and to avoid bias, these physicians may not enroll patients or care for patients enrolled in a study on which they serve as Medical Monitor. 4.5 Protocol Activation A protocol is activated when a sufficient number of committed centers receive IRB approval and provide all necessary documents to the DCC. Each center must provide proof of approval from its IRB and submit required regulatory documents. Centers must also demonstrate proficiency in data submission by reviewing an online training module and completing a post-module practicum. In addition, centers must demonstrate proficiency in preparing electronic manifests for laboratory samples to be shipped by reviewing an online training module and completing a post module quiz. 4.6 Protocol Maintenance 4.6.1 Accrual Monitoring and Intervention The success of a clinical trial depends on timely accrual, which is influenced by many factors. To ensure that problems relating to accrual are minimized, and promptly identified and addressed if they occur, the Protocol Team develops an accrual plan that includes monitoring accrual milestones, planning and holding trial promotion events, and assessing off-protocol transplantation activity through data obtained from the CIBMTR Research Database. Additionally, Core Centers receive a quarterly report that compares their actual versus projected accrual to each protocol.

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 4.0 Concept to Publication: The Protocol Process

When accrual to a study lags, the Protocol Team intervenes quickly to identify and resolve delays. These actions may include:  Reviewing the denominator of total transplants performed in patients potentially fulfilling clinical trial eligibility from the CIBMTR Research Database;  Holding calls or meetings with investigators to discuss accrual challenges and strategies;  Resending accrual surveys to participating centers to obtain new or revised accrual projections;  Asking centers to complete monthly screening reports;  Amending the protocol to address unanticipated accrual barriers;  Submitting regular study update emails to participating center investigators and coordinators to highlight current and target accrual;  Contacting investigators from participating centers that have not enrolled patients to encourage them to enroll;  Preparing protocol-specific educational materials to facilitate accrual;  Recruiting additional centers. Among the eight Network-led protocols currently open, the overall accrual rate is at 106% of target projections. 4.6.1.1 Recruitment of Underrepresented Populations The BMT CTN is committed to the ethical conduct of research involving all eligible patients, including women, minorities, and children. No patients are excluded on the basis of race or sex. Accrual to BMT CTN studies closely mirrors the CIBMTR Research Database in gender and racial composition and is only slightly disparate in pediatric composition (Table 4.1). Table 4.1. Characteristics of subjects enrolled in BMT CTN protocols, 2008-2013, compared to CIBMTR subjects Characteristic BMT CTN CIBMTR Number of Patients 3,429 80,804 Age Median 53 years 54 years ≤ 16 years 7.7% 10.5% > 16 years 92.3% 89.5% Sex Female 42.2% 41.0% Male 57.8% 59.0% Race American Indian / Alaskan Native 0.4% 0.5% Asian 2.8% 3.0% Hawaiian / Pacific Islander 0.3% 0.3% Black or African American 9.8% 10.8% White 84.1% 83.4% Other / Unknown Race 2.6% 2.0%

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 4.0 Concept to Publication: The Protocol Process

Notably, the percentage of males enrolled on BMT CTN protocols from 2008 through 2013 was 57.8%; during this same period, the percentage of male CIBMTR subjects was 59.0%. Males are over represented in the transplant population because several of the common indications for transplant (e.g. multiple myeloma, acute lymphoblastic leukemia, etc.) are either more common in males or have a worse prognosis with standard chemotherapy in males, leading to increased use of transplant, but the number of females reported is more than sufficient to study sex-specific differences in response to therapy. Regarding race, minority patients made up 15.9% of BMT CTN subjects versus 16.6% of CIBMTR subjects, including 2.6% and 2.0% of patients with other / unknown race reported, respectively. The BMT CTN and CIBMTR percentages of minority patients are both lower than the U.S. minority population rate of 22% (US Census 2013 Population Estimates Data) and reflect the overall barriers to transplantation for minority patients. The rates of BMT CTN and CIBMTR pediatric patients differ slightly at 7.7% and 10.5%, respectively. The slightly lower rate of BMT CTN pediatric patient subjects is due in part to large studies involving disease indications more prevalent in adults, studies of treatments that have not been sufficiently tested in children for inclusion in multicenter studies, and studies involving quality of life or comprehension primary endpoints for which there are not pediatric evaluation materials available. Additionally, pediatric patients have access to large transplant trials through the COG, and the BMT CTN is careful not to compete with these. As noted below, the BMT CTN has made and continues to make concerted efforts to increase pediatric participation on its studies and offers pediatric-specific studies in its portfolio. During this reporting period, the Network continued several initiatives to increase recruitment of underrepresented populations:  Double Accrual Credit for Non-Caucasian and Pediatric Patients Enrolled on BMT CTN 1202 and Accrual Closure of Adult Caucasians. The DCC observed that the average monthly Caucasian enrollment rate on the BMT CTN 1202 Biomarkers trial was approximately 87%, which is higher than anticipated and higher than the NIH standard of 75%. To boost accrual of non-Caucasian adults and children, the DCC provided double accrual credit for non-Caucasian patients enrolled on the BMT CTN 1202 study beginning in February 2015. Comparison of the accrual data from January to February 2015 suggested the accrual credit incentive was effective; however, before it could be fully evaluated, the accrual target of 1,500 patients was met. The protocol team decided that additional pediatric and minority patients would be beneficial for the analyses, so they proposed closure of enrollment to Caucasian adults and the study remain open until at least 200 pediatric and 200 African American patients were enrolled. The Data and Safety Monitoring Board approved the proposal, and in April, the study was closed to Caucasian adults. Double accrual credit continued to be offered; in September 2015, the pediatric patient target accrual was met, and enrollment closed to this group. The accrual target for African American patients was met in May 2016. The DCC plans to further explore these approaches for boosting enrollment of underrepresented populations in other protocols.  Participation in RECRUIT Trial. The Network participates in the Randomized Recruitment Intervention Trial (RECRUIT) trial, being conducted by Barbara Tilley, PhD, a statistician at the University of Texas Health Science Center at Houston. The study is funded by a National Institute on Minority Health and Health Disparities grant, which allows for collaboration among other NIH-funded Networks / Groups. The study’s primary objective is to test an intervention targeting clinical trial site investigators and coordinators to increase subject diversity in multi-site treatment trials for diseases that require physician referral. Eleven of the 16 eligible BMT CTN Core Centers agreed to participate. This study, BMT CTN 1505, was activated in the spring of 2015 and will continue until the spring of 2017.  Continued Prioritization of Studies Targeting Underrepresented Populations. The Steering Committee

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 4.0 Concept to Publication: The Protocol Process

carefully considers inclusion of underrepresented patient populations in the Network’s portfolio of studies. Four of the five BMT CTN-led protocols launched this reporting period (multiple myeloma study 1401, GVHD treatment study 1501, aplastic anemia study 1502, and sickle cell disease study 1503) include patients with diseases predominant in minority patients (1401 and 1503), pediatric and adolescent patients (1501, 1502, and 1503), and patients with rare diseases (1502 and 1503). Three of the four other BMT CTN-led studies enrolling patients (1101, 1301, and 1302) include diseases, graft sources, and/or enrollment restrictions that target a higher proportion of minority patients (1101 and 1302) and pediatric and adolescent patients (1301). 4.6.2 Clinical and Laboratory Data Collection One measure of the Network’s success is its efficient and accurate collection, processing, and retrieval of clinical and laboratory data. The Network uses several tools, described in this section, to ensure the integrity of each trial. In doing so, the Network provides the foundation for study results that can be analyzed properly and disseminated for use by physicians caring for patients. 4.6.2.1 AdvantageEDC The Emmes AdvantageEDC system is a Web-based, interactive data entry system, which serves as the Network’s primary data collection tool. To ensure high-quality data collection, the system performs field-level checks during data entry to ensure accuracy, consistency, and completeness of data. If an entry does not pass the validation check or the data do not meet the specified requirements, the system requires the user to resolve the inconsistency. As data are entered, they are maintained in data entry transaction master files, which are periodically processed into master files for analysis. Data entry transaction files are stored separately from the master analysis databases. This procedure provides the statisticians with a stable, fixed dataset for a predetermined period that can be used for multiple or frequently repeated analyses without needing to make private copies. It also pre- processes data for anomalies. Master files are updated nightly and typically stored in SAS® format. These files are the basis for all project reports and analyses. A dynamic forms grid provides an online list of currently submitted, due, and delinquent forms. During the past year, about 35,000 forms were submitted in the AdvantageEDC system for BMT CTN. Accrual reports stratified by center, gender, and ethnicity are updated nightly. Reports summarizing each trial’s progress are updated either weekly or monthly, depending on the report. The DCC developed an integrated, Web-based Severe Adverse Events module. Notification of severe adverse events is provided to key personnel through an automated email system, allowing rapid dissemination of critical information to the Medical Monitor. Source data regarding severe adverse events is available to Medical Monitors, and review of severe adverse events is incorporated into the data system. Integration of medical monitoring functionality in the data entry system facilitates rapid review and reporting of events to study sponsors and regulatory bodies. Adverse events are MedDRA coded to coincide with regulatory reporting through the integrated, Web-based module. 4.6.2.2 Specimen Tracking with GlobalTrace and Staff GlobalTrace is a proprietary Emmes product that the Network uses for all studies. This product is a unique, Web-based application for specimen tracking, inventory, and shipping. It uses bar-coded specimen labels to improve the reliability of specimen inventories by tracking individual samples shipped to either project laboratories or a repository. Individual centers and the NMDP/Be The Match Repository can use GlobalTrace to generate electronic manifests and trace / track each individual specimen. The application allows the study

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 4.0 Concept to Publication: The Protocol Process management team to know in real-time which specimens were collected, where they are, and when they were received by the NMDP/Be The Match Repository. This system has been used by the BMT CTN for more than 10 years for several clinical trials. Online GlobalTrace application training and competency assessment modules are available on the secured BMT CTN website for all new laboratory, biorepository, and clinical site staff. Clinical site and laboratory-specific GlobalTrace user guides can be easily accessed from the AdvantageEDC website to review functionality of specific elements of procedures related to this system. In addition to GlobalTrace, the DCC also has a unique asset in the HCT-knowledgeable staff at the CIBMTR and NMDP/Be The Match Research Sample Repository / Central Processing Laboratory. The Repository staff maintains a local database of processed and stored Network inventory that supports DCC queries. 4.6.2.3 CIBMTR Data Reporting All transplant centers in the US, including Network centers, are required by law to report pre-and post- transplantation clinical data on allogeneic HCT recipients to the Stem Cell Transplant Outcomes Database, which is a component of the C.W. Bill Young Cell Transplantation Program and is managed by the CIBMTR. The Network stipulates that Core and Affiliate Centers must also report similar data for autologous transplant recipients. Some pre-and post-HCT information collected by the CIBMTR is deliberately not captured by AdvantageEDC but rather is transferred from the CIBMTR Research Database to the Emmes database for incorporation into study files. All long term follow-up for Network studies (beyond the primary and secondary endpoints) is captured through CIBMTR report forms to avoid a duplicative long term follow-up program. The Network is committed to maximizing bidirectional data sharing between the databases, AdvantageEDC (Emmes) and FormsNet™ (CIBMTR), as a means of minimizing transplant center reporting burden. The CIBMTR collects data at two levels: A Transplant Essential Data level and a Comprehensive Report Form level. The Transplant Essential Data set contains a limited number of key variables for all consecutive transplant recipients. The Comprehensive Report Form data set captures additional patient, disease, and treatment-related data. Comprehensive Report Form level data is collected for most BMT CTN studies. The CIBMTR reimburses centers for all completed Comprehensive Report Forms utilizing a variety of funding sources, including the CIBMTR’s U24 grant. During this reporting period, more than 5,600 CIBMTR forms were submitted for patients enrolled on BMT CTN studies. A detailed description of CIBMTR data collection procedures is available at cibmtr.org/DataManagement. 4.6.3 Data Audits Data quality is critical to the BMT CTN’s success and is an important element for assessing transplant center performance. Data audits are performed at actively enrolling centers at least once every three years and as often as biannually for centers with high enrollment. Additional data audit site visits may be performed based on site performance or other issues identified during monitoring site visits or data review. These visits provide an opportunity for information exchange between the centers and the DCC as well as an opportunity to provide continuing education on protocol adherence and case report forms completion to help maximize data and overall study quality. During the past year, the DCC conducted data audit site visits at 32 BMT CTN centers. The Auditors / Protocol Monitors evaluated data submission compliance (missing forms / missing values completion / queries), laboratory sample compliance (collection and shipment of protocol-defined research samples), regulatory compliance, protocol compliance, and data quality.

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 4.0 Concept to Publication: The Protocol Process

Reports are issued to the participating transplant centers after each visit, detailing what was reviewed during the visit, such as regulatory files, pharmacy procedures, laboratory compliance, forms completion, and data accuracy. Findings from the visit, as well as an action items list, are included in the report, and center staff members are expected to successfully address all action items before the site visit is considered complete. Reports are reviewed by the NHLBI and DCC and referred to the Executive Committee if results are below expectations or other issues of concern are identified. 4.6.4 Amendments Protocol amendments are necessary for a variety of reasons, including clarifying eligibility criteria and study procedures, addressing unexpected toxicities, and improving accrual. The Protocol Coordinator, in consultation with the Protocol Team, drafts amendments and coordinates the Data and Safety Monitoring Board approval process. Like the initial protocol, the two Protocol Chairs and the Protocol Officer review the protocol amendment a final time, using a review checklist. The DCC ensures that centers have the most current amendments and provides training, if necessary, for changes in study procedures. 4.7 Study Completion 4.7.1 Notice to Cease Enrollment As a trial nears its accrual goal, a memo is sent to each participating center notifying them of the closing date, after which no patient may be enrolled. Centers are required to maintain IRB approval for each study that has completed accrual until follow-up is finished, endpoint data review is complete, the first manuscript is published, and the BMT CTN DCC protocol coordinator has notified the site that it is appropriate to permanently close the study with their IRB. 4.7.2 Follow-up Data Collection after Closure Once the protocol has closed to accrual, centers may be queried by the Endpoint Review Committee to submit outstanding report forms, follow-up data, or source documentation. 4.7.3 Data Review and Analysis The Endpoint Review Committee provides an independent review of submitted data. The Committee consists of an independent panel of physicians, usually including the Protocol Chair and Protocol Officer; a DCC Statistician; and a DCC Coordinator. To conduct an Endpoint Review, the Committee:  Establishes an Endpoint Review Committee Charter to define the review scope and procedure;  Determines the rules for endpoints adjudications;  Conducts central review of Case Report Forms and source documents;  Clarifies discrepant information;  Reviews complex grading or staging of clinical conditions, such as GVHD and disease status;  Adjudicates complex endpoints, such as primary cause of death. Endpoint Review Committees examine the study data in a blinded manner and meet regularly via phone or in- person to reach consensus; the DCC coordinator records adjudicated data in the data system. Source documents and clinical notes are provided by the participating sites, as needed, to facilitate the Endpoint Review. All data discrepancies identified during the review are resolved prior to the data lock for final analyses and primary publication. As of March 31, 2017, Endpoint Reviews were completed for 18 protocols (0101, 0102, 0201, 0301, 0302, 0303, 0401, 0402, 0403, 0501, 0601, 0603, 0604, 0701, 0801, 0802, 0803, and 0901). Each protocol-specific Endpoint

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 4.0 Concept to Publication: The Protocol Process

Review Committee retrospectively reviewed all study data related to the primary endpoint, and most important secondary endpoints, for each study participant. The primary manuscripts were published for 17 of these studies. The primary results manuscript for protocol 0801 is expected during the next reporting period. Endpoint Review Committees were also established to prospectively conduct data review for protocols 0702 and 1202 to ensure the study data regarding myeloma disease (0702) and acute GVHD (1202) are submitted accurately. For protocol 0702, the Endpoint Review Committee completed the review of the primary endpoint in October 2016, and the results were presented as a late-breaking oral abstract at the 2016 ASH Annual Meeting. For protocol 1202, the Endpoint Review Committee review is ongoing, and results are expected in the next reporting period. When centers have provided all required data and data review is complete, the dataset is locked for analysis. The DCC completes data analysis and prepares reports in accordance with the Statistical Analysis Plan (Section 4.2.2). Upon completion of the statistical analysis, the DCC issues an analysis report (technical data report) for the study. In general, the analysis report is available within two months of locking the trial dataset. Study results are available for presentation after final analyses are reviewed by the Protocol Team, Endpoint Review Committee, and Steering Committee. 4.8 Dissemination of Results Substantial effort is made by Protocol Teams to move forward quickly with manuscript preparation. When completed, the Publications Committee reviews proposed publications and presentations to ensure scientific validity and appropriate authorship and acknowledgements. 4.8.1 Authorship Network authorship guidelines are outlined in the Administrative Manual of Procedures, which is available on the public website (bmtctn.net). Authorship status is based on intellectual input and effort throughout the lifecycle of the trial. The Publications Committee maintains authorship policy guidelines, which are ratified by the Steering Committee and consistent with American Medical Association guidelines. Authorship credit on BMT CTN publications is a privilege commensurate with both personal and center contribution to the research, including:  Membership and active participation on the Protocol Team;  Active accrual to the protocol;  Timely and accurate reporting of data;  Active participation in data review and analysis. These activities may involve participation in hypothesis generation, concept development, protocol development, study implementation, subject enrollment, data collection, data analysis, and manuscript preparation. 4.9 Ancillary and Correlative Studies BMT CTN ancillary studies use data, biospecimens, and/or analyses that are outside the main objectives of the primary study. Within the BMT CTN, many ancillary studies are protocol-defined, but some are independent (not included in the primary protocol). Independent ancillary studies must be reviewed and endorsed by the Protocol Team and Biomarkers Committee, if applicable, and approved by the Executive or Steering Committee before the Network can endorse them. Figure 4.2 illustrates this process. A one-page summary document, which outlines these BMT CTN procedures, associated requesting clinical data or biospecimens for ancillary laboratory studies, and the review of study proposal concepts by the Biomarkers and Executive / Steering Committees can

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 4.0 Concept to Publication: The Protocol Process also be found on the Network’s public website (https://web.emmes.com/study/bmt2/ResearchSample.html). Prioritization depends on scientific merit, complexity of the request, and available resources. The goal of the Network is to make its data and specimens as available as possible to investigators to allow important questions to be addressed and, thereby, enhance the worth of NIH’s investment in the BMT CTN. A description of available BMT CTN trial data and summaries of available research biospecimen collections is available on the Network’s public website as a resource for investigators planning correlative and ancillary studies. This website section summarizes the planned data and sample collection schedules and sample processing, and it lists biological samples available for all BMT CTN studies by time point and sample type. Many patients enrolled in BMT CTN trials also contributed pre-transplant biospecimens to the CIBMTR Biorepository. These linked biospecimen collections represent a unique opportunity for investigators to propose a wide range of correlative laboratory study investigations associated with HCT. In 2015, a new resource was created on the CIBMTR public website (cibmtr.org) to provide research investigators with linked BMT CTN / CIBMTR biospecimen inventory summaries associated with BMT transplant study patients who have submitted biospecimens to both collections. To promote the use of BMT CTN biospecimen and clinical data resources, direct links on the CIBMTR website to the BMT CTN resources were added to provide investigators access to comprehensive biospecimen and clinical trial data summaries for future study planning. Procedures were developed for investigators to submit study proposals requesting linked biospecimens and associated clinical data from both the BMT CTN and CIBMTR collections. Proposals will be reviewed and approved primarily through established BMT CTN procedures; however, this process will also involve working closely with the CIBMTR to assess sample availability and obtain all necessary approvals for the linked biospecimens and associated clinical data for approved studies. Figure 4.2. Ancillary study proposal approval process

Proposals utilizing samples or data from BMT CTN Ancillary a specific protocol Protocol Steering/Exec Proposal Team Committees Secondary Review Primary Review

Biomarkers DCC Committee External Proposals utilizing samples or Reviewers data from multiple trials Expert review of methodologies Oversight of all biospecimen-related ancillary studies

Correlative studies are defined in the protocol, and ancillary laboratory or secondary data analyses performed after the primary analysis is complete. Funding for ancillary and correlative studies may come from Network resources or non-Network public or private funding agencies.

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 4.0 Concept to Publication: The Protocol Process

During this reporting period, there were 30 BMT CTN protocol-defined correlative or ancillary studies proposed or ongoing. The Network’s protocol-defined correlative and ancillary studies in progress are described in Table 4.2a. Reporting period updates are listed in bold font. Table 4.2a. Correlative and ancillary studies in progress

Correlative and Ancillary Studies in Progress

Protocol Project Status Laboratory / Location

 Protocol-defined correlative study  Research samples shipped  Investigational fungal diagnostic Clinical data file received from NHLBI / BMT CTN University of Florida assays to diagnose Aspergillus BioLINCC; data conversion and migration to 0101 College of Medicine and other infections another database, with associated query / reporting tool set, completed  Design and initiation of various studies in progress  Ancillary study completed Assessment of microRNA BMT CTN  The Ohio State expression in acute graft- Manuscript in preparation describing the 0101 University versus-host disease miR-29a biomarker and relationship with acute GVHD using BMT CTN patient samples

Combined long term follow-up  Ancillary study BMT CTN and patient quality of life  Data analysis nearing completion 0102 Protocol Team 0102 analysis  Manuscript draft in progress

Meta-analysis including 0102  Ancillary study data: Patient data meta-  Study approved by Executive Committee BMT CTN analysis of trials comparing University of Alabama 0102 tandem auto with sequential  Research materials distribution agreement auto and allo HCT in upfront being finalized and data set preparation being treatment of multiple myeloma discussed Immune reconstitution studies  Immunophenotype assays of lymphoid subsets and  Protocol-defined correlative study BMT CTN dendritic cells Emory University  Data analysis in progress by EK Waller, B 0201  Assays for antigen-specific T Winship Cancer Institute Logan, et al. cells  TREC assay for de novo T cell generation Laboratory: Esoterix  Protocol-defined correlative studies led by EK Clinical Trials Services BMT CTN Immune reconstitution studies Waller (Division of LabCorp) 0201  Antibody and cytokine levels  Data analysis in progress by EK Waller, B Data Analysis: Emory Logan, et al. University Winship Cancer Institute

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 4.0 Concept to Publication: The Protocol Process

Correlative and Ancillary Studies in Progress

Protocol Project Status Laboratory / Location

 Ancillary study analysis led by M Horowitz and N Khera completed BMT CTN Impact on donor selection /  Results presented as oral abstract at 2017 0201 Protocol Team 0201 failure to change practice BMT Tandem Meetings by N Khera  Manuscript draft in progress  Ancillary study analysis led by G Switzer BMT CTN Late donor symptoms  0201 Protocol Team 0201 Data analysis completed, and manuscript in progress BMT CTN 0302, 0402 Validation of a microRNA & 0802 signature for the prediction,  RFA award ancillary study led by Y He Duke University RFA diagnosis, and prognosis of  Manuscript / brief report near completion Funded acute graft-versus-host disease Study  RFA award ancillary study led by S Holtan o Aim 1: Completed and three manuscripts in preparation or completed . Low EGF in myeloablative allotransplantation: Association with severe acute GVHD – accepted, in press in BMT . Follistatin and endoglin: Potential biomarkers of endothelial damage – resubmitting to BMT BMT CTN Inflammation, endothelial . Composite score of FS and sEng at 0402 RFA damage, and angiogenesis after day +28 and NRM – presented at University of Minnesota Funded HCT: A biomarker study of BMT 2017 BMT Tandem Meetings and Study CTN 0402 manuscript being presented o Aim 2: Relationship between soluble VEGF receptors, VEGF ligands, and clinical outcomes post-HCT: Completed with manuscript in preparation; results reported in oral abstract at 2016 BMT Tandem Meetings by L Newell o Aim 3: Relationship of follistatin and activin-A in post-HCT outcomes – completed and results incorporate in third Aim 1 manuscript

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 4.0 Concept to Publication: The Protocol Process

Correlative and Ancillary Studies in Progress

Protocol Project Status Laboratory / Location

 Protocol-defined correlative study Laboratory: Esoterix  Testing completed, and final dataset provided Clinical Trials Services BMT CTN Immune reconstitution studies - to Protocol Team for analysis (Division of LabCorp) 0402 immunophenotyping  Data analysis in progress led by H Kim and Study Analysis: DFCI and C Cutler Harvard Allogeneic HY antibodies BMT CTN detected 3 months following 0402 & sex-mismatched HCT predict  RFA award ancillary study led by D Miklos 0201 RFA Stanford University chronic GVHD and non-relapse Funded  Study nearing completion mortality: A BMT CTN validation Study study Proteomic and genomic analysis  Protocol-defined correlative study led by K BMT CTN of plasma and genomic cytokine Cooke Johns Hopkins University 0403 and inflammatory markers  In progress  Protocol-defined correlative studies  Testing and result dataset verification BMT CTN Immune reconstitution studies completed Duke University 0501  Study team assembled and data analysis in progress  Ancillary study led by L Metheny  Trial data ERC adjudication nearing completion Case Western Reserve BMT CTN Obesity and multiple myeloma  Study in progress – testing and initial data University School of 0702 ancillary study analysis completed; waiting for final Medicine adjudicated outcomes to become available to complete study analysis Analysis of MRD by NGS and  Ancillary study led by A Garfall BMT CTN correlation with flow MRD University of 0702 monitoring in PRIMeR study and  Study in progress – baseline marrow samples Pennsylvania with patient outcomes received and testing initiated Laboratory: Roswell Park PRIMeR study: Minimal residual  Ancillary study Cancer Institute (RPCI) BMT CTN disease in multiple myeloma by  Patient sample testing completed Study Analysis: RPCI and 0702 flow cytometry  Data analysis in progress Medical College of Wisconsin

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 4.0 Concept to Publication: The Protocol Process

Correlative and Ancillary Studies in Progress

Protocol Project Status Laboratory / Location

Laboratory: Dana-Farber Cancer Institute Regulatory T cell / B cell  Protocol-defined correlative study Study Analysis: Fred BMT CTN immunophenotyping and B cell  Testing completed Hutchinson Cancer 0801 activating factor biomarker Research Center and levels by ELISA  Protocol Team to begin data analysis soon University of Minnesota Assessments of TCR diversity in HCT recipients at the time of diagnosis of GVHD and BMT CTN relatedness of TCR sequences  RFA award ancillary study led by E Meyer 0802 RFA between subsets of patients  Testing completed Stanford University Funded based upon shared  Study analysis and manuscript preparation Study characteristics, such as female underway donors into male recipients, HLA, or specific HLA mismatches  Protocol-defined correlative study BMT CTN Microbial translocation marker  Testing completed University of North 0803 measurements  Protocol Team-led data analysis plan in Carolina progress Characterization of HIV infection in AIDS-related  Protocol-defined correlative study malignancies: BMT CTN  Sample testing completed  HIV single-copy HIV viral Johns Hopkins University 0803 titer measurements  Protocol Team-led data analysis plan in progress  Plasma DNA tumor monitoring  Protocol-defined correlative study Immunophenotypic and BMT CTN  Testing completed functional characterization of Ohio State University 0803 immune reconstitution  Draft manuscript completed and circulated to authors for comment

 Protocol-defined correlative study Seattle Cancer Care BMT CTN Busulfan pharmacokinetics  Testing completed and final dataset provided Alliance 0901 study  Study analysis near completion Pharmacokinetics  Manuscript planning underway Laboratory

Severity, course, and predictors  Ancillary study led by H Jim BMT CTN H. Lee Moffitt Cancer of sleep disruption following  Trial dataset provided 0902 Center autologous HCT  Secondary data analysis in progress

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 4.0 Concept to Publication: The Protocol Process

Correlative and Ancillary Studies in Progress

Protocol Project Status Laboratory / Location

Immunophenotypic and BMT CTN  Protocol-defined correlative study functional characterization of Ohio State University 0903  immune reconstitution In progress BMT CTN Microbial translocation marker  Protocol-defined correlative study University of North 0903 measurements  In progress Carolina Characterization of HIV BMT CTN  Protocol-defined correlative study infection and latent HIV Johns Hopkins University 0903 reservoirs  In progress Characterization of HIV infection in AIDS-related BMT CTN  Protocol-defined correlative study malignancies: HIV single-copy University of Pittsburgh 0903 HIV viral titer measurements  In progress (PBMC & plasma)  Companion sub-study to BMT CTN 1101 and BMT CTN Determine cost-effectiveness 1102 Fred Hutchinson Cancer 1101 & expressed as cost per quality Research Center 1102 adjusted life year  Currently accruing patients enrolled on BMT CTN 1101 and 1102 BMT CTN Perspective: Real-time acute  Analysis and manuscript preparation led by 1202 Protocol Team 1202 GVHD clinical data adjudication J Levine, R Reshef, and J Hansen

Nine ancillary studies were completed this reporting period, bringing the total number of completed protocol-defined correlative or ancillary studies to 25. These studies are described in Table 4.2b. Reporting period updates are listed in bold font. Table 4.2b. Correlative and ancillary studies completed

Correlative and Ancillary Studies Completed

Protocol Project Status Laboratory/Location

 Ancillary study Cost-effectiveness analysis of  Study completed voriconazole compared with  Cost-effectiveness analysis of voriconazole BMT CTN fluconazole for prevention of compared with fluconazole for prevention RTI Health Solutions 0101 invasive fungal infection after of invasive fungal infection in patients allogeneic hematopoietic cell receiving allogeneic HCT. American Journal transplantation of Health-System Pharmacy. 2013 Sept 1; 70(17):1518-1527

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 4.0 Concept to Publication: The Protocol Process

Correlative and Ancillary Studies Completed

Protocol Project Status Laboratory/Location

 Protocol-defined correlative study Antimicrobial  Study completed Pharmacokinetic studies of Pharmacodynamics  voriconazole and fluconazole Results presented at 2014 ICAAC meeting and Therapeutics BMT CTN administered for prevention of by W Hope, et al. Laboratory 0101 invasive fungal infections in  Voriconazole pharmacokinetics following Department of allogeneic blood and marrow HCT: Results from the BMT CTN 0101 trial. Molecular and Clinical transplant recipients Journal of Antimicrobial Chemotherapy. Pharmacology 2016 Aug 1; 71(8):2234-2240. Epub 2016 University of Liverpool Apr 27  Ancillary study  Study completed  Initial results presented at ASH in 2011 by P Hari, et al. Free light chain analysis in  Long term follow-up results presented at patients undergoing autologous BMT CTN 2015 European Hematology Association or allogeneic hematopoietic stem The Binding Site 0102 meeting by A D’Souza, et al. cell transplantation for multiple  Heavy / light chain ratio normalization myeloma prior to transplant is of independent prognostic significance in multiple myeloma: A BMT CTN 0102 correlative study. British Journal of Haematology. 2016 Jun 13. [Epub ahead of print]  Protocol-defined correlative study  Results presented at ASH in 2011 by EK Waller, et al. Emory University BMT CTN Immune reconstitution studies  Improved survival after transplantation of Winship Cancer 0201 Donor HCT graft characterization more donor plasmacytoid dendritic or naïve T cells from unrelated-donor marrow Institute grafts: results from BMT CTN 0201. Journal of Clinical Oncology. 2014 Aug 1; 32(22):2365-2372. Epub 2014 Jun 30

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 4.0 Concept to Publication: The Protocol Process

Correlative and Ancillary Studies Completed

Protocol Project Status Laboratory/Location

 Protocol-defined correlative study Health-related quality of life of  bone marrow versus peripheral Health-related QoL of bone marrow vs. BMT CTN blood stem cell donors: a pre- PBSC donors: a pre-specified subgroup University of Pittsburgh 0201 specified subgroup analysis from analysis from a Phase III RCT-BMT CTN a Phase III RCT – BMT CTN protocol 0201. Biology of Blood and Protocol 0201 Marrow Transplantation. 2014 Jan 1; 20(1):118-127. Epub 2013 Nov 1  Protocol-defined correlative study  Results presented at 2016 EBMT Annual Meeting by L Burns, et al.  Recovery of unrelated donors of PBSC vs. BMT CTN Donor Clinical Manuscript / recovery of unrelated donors of bone 0201 Protocol Team 0201 Donor as a Research Subject marrow: A pre-specified analysis from the Phase III BMT CTN protocol 0201. Biology of Blood and Marrow Transplantation. 2016 Jun 1; 22(6):1108-1116. Epub 2016 Mar 21  Protocol-defined correlative study Analysis of infectious  Results presented at 2015 BMT Tandem complications related to Meetings by J Young, et al. patients’ clinical risk, comparing BMT CTN two treatment cohorts  Infections following transplantation of University of Minnesota 0201 (peripheral blood stem cell bone marrow or PBSC from unrelated versus marrow) and adjusting for donors. Biology of Blood and Marrow other relevant clinical risk factors Transplantation. 2016 Feb 1; 22(2):359- 370. Epub 2015 Sep 25  Ancillary study analysis led by S Lee  Results presented at 2015 ASH meeting by S Lee, et al.  Comparison of patient-reported BMT CTN Patient quality of life – 5-year outcomes in 5-year survivors who 0201 Protocol Team 0201 follow-up received bone marrow vs peripheral blood unrelated donor transplantation (long-term follow-up of a randomized clinical trial). JAMA Oncology. 2016 Dec 1; 2(12):1583-1589. Epub 2016 Aug 11

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 4.0 Concept to Publication: The Protocol Process

Correlative and Ancillary Studies Completed

Protocol Project Status Laboratory/Location

 Protocol-defined correlative study  Study completed  Results presented at EBMT Annual BMT CTN Analysis of serum biomarkers Meeting in 2011 by JE Levine, et al. University of Michigan 0302 during treatment of acute GVHD  Acute GVHD biomarkers measured during therapy can predict treatment outcomes: A BMT CTN study. Blood. 2012 Apr 19; 119(16):3854-3860. Epub 2012 Mar 1  Protocol-defined correlative study  Study completed Mycophenolate pharmacokinetics BMT CTN and association with response to  Mycophenolate pharmacokinetics and University of Minnesota 0302 acute GVHD treatment from the association with response to acute GVHD BMT CTN treatment from the BMT CTN. Biology of Blood and Marrow Transplantation. 2010 Mar 1; 16(3):421-429  Correlative study  Study completed BMT CTN Graft-versus-host disease  GVHD treatment: predictors of survival. N/A 0302 treatment: predictors of survival Biology of Blood and Marrow Transplantation. 2010 Dec 1; 16(12):1693- 1699. Epub 2010 Jun 10  Correlative study  Study completed Lymphocyte phenotype during BMT CTN therapy for acute graft versus  Lymphocyte phenotype during therapy for N/A 0302 host disease: a brief report from acute GVHD: a brief report from BMT-CTN BMT CTN 0302 0302. Biology of Blood and Marrow Transplantation. 2013 Mar 1; 19(3):481- 485. Epub 2012 Dec 12  Revised protocol-defined correlative study Pharmacogenetics of steroid  Study completed BMT CTN responsive acute graft-versus- University of Minnesota 0302  Pharmacogenetics of steroid-responsive host disease acute GVHD. Clinical Transplantation. 2017 Mar 7. [Epub ahead of print]

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 4.0 Concept to Publication: The Protocol Process

Correlative and Ancillary Studies Completed

Protocol Project Status Laboratory/Location

 Correlative study  Study completed Characteristics of CliniMACS(®) system CD34-enriched T cell-  Characteristics of CliniMACS(®) System BMT CTN depleted grafts in a multicenter CD34-enriched T cell-depleted grafts in a N/A 0303 trial for acute myeloid leukemia- multicenter trial for AML – BMT CTN BMT CTN protocol 0303 protocol 0303. Biology of Blood and Marrow Transplantation. 2012 May 1; 18(5):690-697. Epub 2011 Aug 26

Comparative outcomes of donor  Correlative study graft CD34+ selection and  Study completed immune suppressive therapy as graft-versus-host disease  Comparative outcomes of donor graft BMT CTN prophylaxis for patients with CD34+ selection and immune suppressive N/A 0303 acute myeloid leukemia in therapy as GVHD prophylaxis for patients complete remission undergoing with AML in complete remission HLA-matched sibling allogeneic undergoing HLA-matched sibling allogeneic hematopoietic cell HCT. Journal of Clinical Oncology. 2012 Sep transplantation 10; 30(26):3194-3201  Ancillary study Validation of a six-biomarker  Study completed panel for the prediction of acute BMT CTN  Plasma biomarkers of risk for death in a or chronic GVHD and correlations Indiana University 0402 multicenter Phase 3 trial with uniform with day 365 non-relapse transplant characteristics post-allogeneic mortality HCT. Blood. 2017 Jan 12; 192(2):162-170. Epub 2016 Nov 8  Ancillary study  Circulating angiogenic factors associated Angiogenic biomarkers of acute BMT CTN with response and survival in patients with GVHD (utilizing 0302/0802 University of Minnesota 0802 / 0302 acute GVHD: Results from BMT CTN 0302 samples) and 0802. Biology of Blood and Marrow Transplantation. 2015 Jun 1; 21(6):1029- 1036. Epub 2015 Mar 7  Ancillary study Extended acute GVHD biomarker  BMT CTN testing and Ann Arbor GVHD A prognostic score for acute GVHD based University of Michigan 0802 / 0302 scoring validation (utilizing 0802 / on biomarkers: A multicentre study. Lancet 0302 samples) Haematology. 2015 Jan 1; 2(1):e21-29. Epub 2014 Dec 23

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 4.0 Concept to Publication: The Protocol Process

Correlative and Ancillary Studies Completed

Protocol Project Status Laboratory/Location

 Ancillary study  A refined risk score for acute GVHD that BMT CTN Acute GVHD risk score (utilizing predicts response to initial therapy, University of Minnesota 0802 / 0302 0802 / 0302 samples) survival, and transplant-related mortality. Biology of Blood and Marrow Transplantation. 2015 Apr 1; 21(4):761-767. Epub 2015 Jan 10  Ancillary study led by W Wood Baseline SF36 independent BMT CTN  Patient-reported physical functioning University of North prognostic factors for overall 0902 predicts the success of HCT (BMT CTN Carolina survival 0902). Cancer. 2016 Jan 1; 122(1):91-98. Epub 2015 Oct 6  Ancillary study led by J Wingard  Pretransplantation exercise and HCT BMT CTN University of Florida Pre-transplant exercise survival: A secondary analysis of BMT CTN 0902 0902. Biology of Blood and Marrow College of Medicine Transplantation. 2017 Jan 1; 23(1):161- 164. Epub 2016 Oct 11  Ancillary study led by K Syrjala  Abstract presented at the 2015 IPOS / APOS World Congress on Psycho-Oncology by K Syrjala, et al. BMT CTN Psychometrics of cancer and Fred Hutchinson Cancer 0902 treatment-related distress data  Cancer and treatment distress Research Center psychometric evaluation over time: A BMT CTN 0902 secondary analysis. Cancer. 2017 Apr 15; 123(8):1416-1423. Epub 2016 Nov 28  Ancillary study led by H Jim  Trajectories of quality of life after HCT: BMT CTN Patterns of quality of life after Secondary analysis of BMT CTN 0902 H. Lee Moffitt Cancer 0902 transplant data. Biology of Blood and Marrow Center Transplantation. 2016 Nov 1; 22(11):2077–2083. Epub 2016 Aug 15

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 4.0 Concept to Publication: The Protocol Process

Correlative and Ancillary Studies Completed

Protocol Project Status Laboratory/Location

 Ancillary study led by J Knight  Abstract presented at the 2015 IPOS/APOS World Congress on Psycho-Oncology by J Knight, et al. Pre-transplant health-related BMT CTN Medical College of quality of life factors as predictors  Patient-reported outcomes and 0902 Wisconsin of outcomes following HCT socioeconomic status as predictors of clinical outcomes after HCT: A study from the BMT CTN 0902 trial. Biology of Blood and Marrow Transplantation. 2016 Dec 1; 22(12):2256-2263. Epub 2016 Aug 23  Design of a cost-effectiveness analysis alongside a randomized trial of transplantation using UCB vs. HLA- BMT CTN Cost-effective analysis methods Fred Hutchinson Cancer haploidentical related bone marrow in 1101 paper Research Center advanced hematologic cancer. Journal of Comparative Effectiveness Research. 2014 Mar 1; 3(2):135-144

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 5.0 Collaborations with other NIH-funded Research Networks 5.0 Collaborations with other NIH-funded Research Networks

The mission of the BMT CTN overlaps with the mission of NCI-sponsored National Clinical Trials Network as well as other NIH-sponsored networks and investigators. A major responsibility of DCC leadership is to enhance communication among these groups to minimize the number of competing trials and to foster collaboration to decrease the time required to complete studies. To that end, the Network has:  Collaborated and shared accrual on 16 protocols: o BMT CTN-led studies: . BMT CTN 0102 – SWOG . BMT CTN 0401 – SWOG . BMT CTN 0501 – COG . BMT CTN 0601 – Sickle Cell Disease Clinical Research Network and NIH’s National Center for Minority Health and Health Disparities . BMT CTN 0701 – Alliance for Clinical Trials in Oncology, ECOG-ACRIN Cancer Research Group, SWOG . BMT CTN 0702 – Alliance for Clinical Trials in Oncology, ECOG-ACRIN Cancer Research Group, SWOG . BMT CTN 0803 – AIDS Malignancy Consortium . BMT CTN 0903 – AIDS Malignancy Consortium o National Clinical Trials Network Group-led studies: . Alliance for Clinical Trials in Oncology / CALGB 100103 – BMT CTN 0502 . SWOG 0410 – BMT CTN 0703 . Alliance for Clinical Trials in Oncology / CALGB 100104 – BMT CTN 0704 . Alliance for Clinical Trials in Oncology / CALGB 100701 – BMT CTN 0804 . SWOG 0805 – BMT CTN 0805 . Alliance for Clinical Trials in Oncology / A051301 – BMT CTN 1201 . DFCI / IFM 10-106 – BMT CTN 1304 . University of Texas RECRUIT – BMT CTN 1505  Implemented a shared national agenda for myeloma transplantation trials that is represented by CALGB 100104 / BMT CTN 0704, BMT CTN 0702, BMT CTN 1302, DFCI 10-106 / BMT CTN 1304, and BMT CTN 1401; this agenda was led by the BMT CTN-initiated Multiple Myeloma Intergroup, including representatives from The Alliance for Clinical Trials in Oncology, ECOG-ACRIN, and SWOG;  Participated in the NCI Lymphoma, Myeloma, and Leukemia Steering Committees;  Included National Clinical Trials Network Group representation on the BMT CTN Steering Committee to promote communication and collaborative partnerships with these groups;  Partnered with the AIDS Malignancy Consortium to support innovative trials for AIDS-associated malignancies (BMT CTN 0803 and 0903).

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 6.0 Future Directions 6.0 Future Directions 6.1 Continued Planning for the Current Grant Cycle Prior to the start of the current grant cycle, a group of BMT CTN leaders met to lay out goals for the DCC and the Network. This group has continued to meet to evaluate ways to enhance the BMT CTN’s proficiency and efficiency, identify optimal uses of funds, and refine processes to promote success and scientific productivity of the Network. It was these leaders, along with the Steering Committee, that determined another State of the Science Symposium should be conducted to survey the HCT landscape and identify greatest areas of need. The 2014 State of the Science Symposium was held in February 2014 during the BMT Tandem Meetings and detailed in the 2014 Progress Report. Updates from the 2007 and 2014 State of the Science Symposiums, including status of prioritized concepts, are provided below. These priority concepts served as a road map for studies recommended for implementation by the US transplant community using the resources of the BMT CTN, NCI Cooperative (now National Clinical Trials Network) Groups, and other programs. As the current grant cycle comes to a close, the BMT CTN leaders re-convened several State of the Science Committees to evaluate new study concepts to be considered for the next grant cycle starting July 1, 2017. Study concepts to be reviewed include those submitted in the Core Center grant applications, concepts already deemed meritorious during the current grant cycle, and prioritized but deferred concepts from the 2014 State of the Science Symposium. Concepts will be presented and discussed at the June 2017 Steering Committee meeting with final decisions regarding implementation made during the July Steering Committee conference call, when the new Steering Committee roster will be finalized. 6.2 State of the Science Symposia 6.2.1 2007 State of the Science Symposium The publication from the Network’s 2007 State of the Science Symposium, listed below, provided prior guidance for high-priority studies to be developed by the Network and/or NCI Cooperative Groups.  Ferrara J, Anasetti C, Stadtmauer E, Antin J, Wingard J, Lee SJ, Levine J, Schultz K, Appelbaum F, Negrin R, Giralt S, Bredeson C, Heslop H and Horowitz M. BMT CTN State of the Science Symposium 2007. Biology of Blood and Marrow Transplantation. 2007 Nov 1; 13:1268-1285. During this reporting period, primary results from two studies (BMT CTN 0901 and SWOG S0805 / BMT CTN 0805) were published. Primary results from another study (BMT CTN 0702) were presented and will be submitted for publication during the next reporting period. Three studies completed enrollment and reached the date of evaluable analysis (BMT CTN 0801, CALGB 100701 / BMT CTN 0804, and BMT CTN 1204); they will be completed during the next reporting period. Table 6.1 displays the status of studies prioritized at the 2007 State of the Science Symposium.

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 6.0 Future Directions

Table 6.1. Status of studies prioritized at the 2007 State of the Science Symposium

Studies Prioritized at the 2007 State of the Science Symposium

BMT CTN Proposal Comments / Status Protocol Number Phase III trial of tandem autologous Accrual was completed in November 2013. The primary transplant versus consolidation with endpoint is progression-free survival as a time to event bortezomib, lenalidomide, and endpoint censored after 38 months of follow-up. The dexamethasone after a single BMT CTN Endpoint Review Committee is finalizing data review. The autologous transplant versus 0702 primary results were presented as a late-breaking abstract maintenance therapy with at the ASH Annual Meeting in December, and the primary lenalidomide after a single autologous results manuscript is being drafted. transplant for myeloma Phase III trial of chemotherapy versus unrelated donor transplantation in Development deferred. N/A patients with high-risk AML in first complete remission This collaborative study is led by SWOG, with active involvement of BMT CTN representatives; accrual was Phase II trial of chemotherapy and completed in October 2013. The primary endpoint is BMT CTN dasatinib versus allogeneic HCT in relapse-free survival at one year. Data analysis was 0805 / SWOG patients with Philadelphia completed during the previous reporting period, and S0805 chromosome positive ALL results presented at 2015 BMT Tandem Meetings. The primary results manuscript was published in November 2016. The primary manuscript was published in Biology of Blood Phase III trial of peri-transplant stress and Marrow Transplantation in June 2014 by PB Jacobsen BMT CTN management versus standard of care et al. Five ancillary analyses were published, four during 0902 this reporting period. One additional analysis is underway. This collaborative study is being led by Alliance, with active Phase II trial of allogeneic HCT with involvement of BMT CTN representatives; accrual was BMT CTN reduced-intensity conditioning in completed in January 2014. The primary endpoint is two- 0804 / CALGB patients with very high-risk CLL year progression-free survival. Data analysis is underway, 100701 and the manuscript will be drafted later in 2017.

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 6.0 Future Directions

Studies Prioritized at the 2007 State of the Science Symposium

BMT CTN Proposal Comments / Status Protocol Number Presented at July 2011 Steering Committee meeting and voted as lower priority as available pilot data not considered adequate. Concept re-presented at the February 2013 Steering Committee meeting and voted as higher priority. Design reconfigured and presented at 2014 State of the Science Symposium. Selected as priority study, Phase II trial of HLA-matched, viral- but not selected to be developed during this reporting Not yet specific cytotoxic T lymphocytes to period. However, two other concepts using third-party applicable treat adenoviral infections donor derived viral-specific T-cell products (for treatment of cytomegalovirus and BK virus, respectively) were proposed during this reporting period and will be re- evaluated at the June 2017 Steering Committee. A tentative protocol for the BK virus study is being developed with support of the ViraCyte Corporation and will be presented as part of that re-evaluation. Accrual to this trial was halted permanently in April 2014 after preliminary data appeared to show benefit for more intensive conditioning for allogeneic HCTs in patients Phase III trial of full-intensity eligible for the study. The primary endpoint of overall conditioning versus reduced-intensity BMT CTN survival at 18 months was completed, and a late-breaking conditioning for allogeneic HCT in 0901 abstract was presented at the annual 2015 ASH Annual recipients with AML ages 30–60 years Meeting as well as at the 2016 BMT Tandem Meetings as a special invite abstract. The primary results manuscript was published in January 2017. Accrual was completed in March 2015, much sooner than expected; consequently, an amendment was requested to expand the sample size from 35 patients total to 35 hemophagocytic lymphohistiocytosis (HLH) patients. Accrual remained open to all patients during the extension. Phase II trial of allogeneic HCT with The protocol was closed to enrollment in December 2015, reduced-intensity conditioning in BMT CTN one year ahead of projections despite the increase in children with hemophagocytic 1204 sample size. A total of 36 HLH patients and 11 patients with syndromes other hemophagocytic disorders enrolled. The primary endpoint is one year overall survival. The Endpoint Review Committee completed their review in November 2016. The final analysis report was provided to the team in April 2017, and the manuscript will be drafted in Summer 2017. Phase II trial of allogeneic HCT with reduced-intensity conditioning as Protocol concept no longer high priority. N/A primary therapy for T-cell lymphoma Phase II trial of autologous HCT for No protocol concept presented to date. N/A refractory Crohn’s disease

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 6.0 Future Directions

Studies Prioritized at the 2007 State of the Science Symposium

BMT CTN Proposal Comments / Status Protocol Number The study was designed as a Phase II/III study. Accrual was closed to enrollment in December 2013 after the Data and Safety Monitoring Board reviewed the Phase II data and determined the Phase III component should not be undertaken per protocol-specified parameters. The primary endpoint is complete or partial response after 6 months of Phase II trial of calcineurin-free GVHD therapy. The Endpoint Review Committee reviewed BMT CTN treatment regimens in patients with the 6-month data of all patients and completed the 0801 high-risk chronic GVHD adjudication of the chronic GVHD response endpoint. The primary results were presented at the 2016 BMT Tandem Meetings. It was determined the 2 year results should be included in the primary results manuscript. The updated analysis report will be provided to the protocol team in April 2017, and the manuscript will be drafted in Summer 2017.

6.2.2 2014 State of the Science Symposium The publication from the BMT CTN’s 2014 State of the Science Symposium, listed below, outlines the high- priority studies to be developed by the Network and/or NCI Cooperative Groups.  Appelbaum F, Anasetti C, Antin J, Atkins H, Davies S, Devine S, Giralt S, Heslop H, Laport G, Lee S, Logan B, Pasquini M, Pulsipher M, Stadtmauer E, Wingard J, Horowitz M. Blood and Marrow Transplant Clinical Trials Network State of the Science Symposium 2014. Biology of Blood and Marrow Transplantation. 2015 Feb 1; 21(2): 202-224. Epub 2014 Oct 14. Following the State of the Science Symposium, the symposium review committee prioritized twelve studies. During this reporting period, the Network activated one protocol (BMT CTN 1501), released a protocol to centers (BMT CTN 1506), and initiated development on another protocol (BMT CTN 1602). There were also continued collaborations on two studies led by other NIH Networks, including the Alliance A051301 / BMT CTN 1201 protocol that was activated during this reporting period. Tables 6.2 and 6.3 display the status of each of the prioritized studies.

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 6.0 Future Directions

Table 6.2. Status of studies prioritized at the 2014 State of the Science Symposium

Studies Prioritized at the 2014 State of the Science Symposium

BMT CTN Proposal Comments / Status Protocol Number The protocol team was formed in July 2015. In March 2016, Leukemia #1: AML: FLT3 inhibition the protocol was approved by the Protocol Review compared to placebo as maintenance BMT CTN Committee. The study received Data and Safety Monitoring therapy after allotransplant for FLT3+ 1506 Board approval in September 2016, and the protocol was AML released to centers in March 2017. Leukemia #2: AML / MDS: low dose Development deferred; additional funding sources being azacytidine maintenance compared to N/A sought. no maintenance Although initially planned as a BMT CTN-led study, it was determined the study was a better fit for the NCI National Clinical Trials Network since the drug was available through Lymphoma #1: Relapsed and refractory NCI’s cooperative research and development agreement BMT CTN diffuse large B cell lymphoma: ibrutinib (CRADA). Alliance is the lead group. It was already in 1201 / vs. placebo during and after autologous development before the symposium, but its identification as Alliance HCT a priority showcased the need for its timely development. A051301 BMT CTN has provided input on the study design throughout the development process. The protocol was released to centers and activated in July 2016. The NIAID committed to the development of this study, which will be conducted by the Immune Tolerance Network Non-Malignant Diseases #1: Multiple (ITN). The BMT CTN will endorse the study and collaborate ITN Sclerosis: autologous HCT vs. best with the NIAID / ITN on protocol development. Study BEAT-MS standard of care development commenced, and the protocol will be finalized in 2017. A Phase II trial of posttransplant moxetumomab was launched by the PBMTC, with help from the DCC, but was Pediatric Transplant – Indications #1: closed for toxicity. Other agents will be considered by the ALL post-HCT with either moxetumomab N/A Pediatric State of the Science Symposium Committee for or inotuzumab presentation at the June 2017 Steering Committee meeting. Development deferred to next funding cycle. The Pediatric Pediatric Transplant – Outcomes #1: State of the Science Symposium Committee will evaluate Daily vs. alternating day dosing of N/A for presentation at the June 2017 Steering Committee steroids in chronic GVHD meeting.

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 6.0 Future Directions

Studies Prioritized at the 2014 State of the Science Symposium

BMT CTN Proposal Comments / Status Protocol Number The Network has committed to evaluating the post- transplant cyclophosphamide / haploidentical donor transplantation approach in the reduced-intensity conditioning setting (1101, and upcoming 1502 and 1507 Optimal Donor and Graft Source #1: protocols). Development of a protocol using myeloablative N/A Post-HCT cyclophosphamide conditioning with haploidentical donors will be considered by the Optimal Donor and Graft Source State of the Science Symposium Committee for presentation at the June 2017 Steering Committee meeting. The GVHD State of the Science Symposium Committee presented several initial study concepts to the Steering Committee in February 2016. Upon further investigation, the committee proposed a Phase I / randomized Phase II GVHD #2a: Acute GVHD treatment for registration study using a JAK-1 inhibition for high risk BMT CTN high risk patients: rand Phase II of 1-2 acute GVHD treatment; the Steering Committee approved 1602 agents vs. control the study in August 2016. Protocol development began in September. The Protocol Review Committee approved the study in February 2017. It is anticipated the protocol will be released in Summer 2017. The protocol was approved by the Protocol Review GVHD #2b: Acute GVHD treatment for Committee in December 2015 and Data and Safety BMT CTN low risk patients: rand Phase II of 1 agent Monitoring Board in February 2016. The protocol was 1501 vs. control released to centers in April 2016 and activated in October 2016. Gene and Cell Therapy #2: This protocol will be developed once data from pilot studies Haploidentical donor natural killer cells are available, anticipated to be in 2018. Potential N/A for AML patients contributions from industry partners are being explored. Comorbidity / Regimen-Related Toxicity Development deferred to next funding cycle. The Leukemia #1: Improving health assessment and and Multiple Myeloma State of the Science Symposium N/A prediction of toxicity / mortality in older Committees will evaluate for presentation at the June 2017 patients undergoing allogeneic HCT Steering Committee meeting. Development deferred to next funding cycle. A concept Infection / Immune Reconstitution #1: using third-party donor derived viral-specific T-cell Cytomegalovirus-specific T cell adoptive products for treatment of cytomegalovirus was initially N/A therapy (joint proposal with Gene and proposed to the Steering Committee in February 2017 and Cell Therapy Committee) will be evaluated with other study concepts at the June 2017 Steering Committee.

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 6.0 Future Directions

Studies Prioritized at the 2014 State of the Science Symposium

BMT CTN Proposal Comments / Status Protocol Number Infection / Immune Reconstitution #2: Development deferred to next funding cycle. The Infection Novel parainfluenza entry inhibitor in and Immune Reconstitution State of the Science N/A HCT recipients with parainfluenza virus Symposium Committee will evaluate for presentation at upper respiratory tract infection the June 2017 Steering Committee meeting. Late Effect / Quality of Life / Economics Development deferred to next funding cycle. The Late Effect #1: Zoledronic acid vs. placebo for / Quality of Life / Economics State of the Science N/A prevention of bone loss after allogeneic Symposium Committees will evaluate for presentation at HCT the June 2017 Steering Committee meeting.

At its February 2015 meeting, the Steering Committee additionally prioritized two studies of transplantation for non-malignant disease for development in 2015, one for aplastic anemia patients and the other for sickle cell disease patients. Each was recommended by the State of the Science Symposium Non-Malignant Disease Subcommittee though not included in the high priority list above. Additionally, the Steering Committee approved a second sickle cell disease study be developed using a different transplant approach. Table 6.3 displays the status of each of the prioritized studies. Table 6.3. Status of studies prioritized after the 2014 State of the Science Symposium

Studies Prioritized after the 2014 State of the Science Symposium

BMT CTN Proposal Comments / Status Protocol Number The protocol team was formed in January 2015. The protocol was approved by the Protocol Review Committee Non-Malignant Diseases: Haploidentical in December 2015. The Data and Safety Monitoring Board BMT CTN bone marrow and/or unrelated cord approved the study in October 2016. The protocol was 1502 blood transplantation for aplastic anemia released to centers in December 2016 and is anticipated to be activated in April 2017. The protocol team was formed in July 2015. The protocol Non-Malignant Diseases: Unrelated was approved by the Protocol Review Committee in donor transplantation vs. standard of December 2015. The Data and Safety Monitoring Board BMT CTN care (biologic assignment) in young approved the study in April 2016. The protocol was 1503 adults with sickle cell anemia released to centers in May 2016 and activated in November 2016. The protocol team was formed in July 2015. The Protocol Non-Malignant Diseases: Haploidentical Review Committee approved the protocol in April 2016. bone marrow transplantation for The protocol was submitted to the Data and Safety BMT CTN children and adults with severe sickle cell Monitoring Board in September 2016. After multiple 1507 disease queries, approval is anticipated in April 2017, and the protocol will be released to centers shortly thereafter.

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 6.0 Future Directions 6.3 Projected Study Activities during the Next Reporting Period 6.3.1 Anticipated Results In the coming year, two trials will reach primary endpoints. The results will be analyzed to address important questions:  BMT CTN 1203. Does the one year GVHD / relapse or progression-free survival differ between patients who receive one of the three novel GVHD prophylaxis approaches being tested versus patients enrolled on the CIBMTR contemporary control arm? Do the results warrant further testing of novel approach(es) in a randomized Phase III study?  UT RECRUIT / BMT CTN 1505. Does the study intervention targeting clinical trial site investigators and coordinators increase enrollment of minority subjects onto BMT CTN studies? Does the intervention increase the number of referrals to transplant centers from community physicians? Additionally, 30 ancillary and correlative studies are in progress (Section 4.9). 6.3.2 Studies Nearing Completion of Accrual Four studies are likely to complete accrual during the next reporting period:  BMT CTN 07LT. Continued, long-term follow-up and lenalidomide maintenance therapy for patients who have enrolled on BMT CTN 0702 o The study was activated in March 2015 as a follow-up maintenance therapy study for patients enrolled on the BMT CTN 0702 study who have not experienced disease progression. Target accrual of approximately 450 patients was anticipated based on assumed progression-free survival estimates from the 0702 study; however, the final accrual will be dependent on the observed rate of progression-free survival on the 0702 study. Accrual is slated to be complete in late 2017.  BMT CTN 1102. A multi-center biologic assignment trial comparing reduced intensity allogeneic hematopoietic cell transplant to hypomethylating therapy or best supportive care in patients aged 50-75 with intermediate-2 and high risk myelodysplastic syndrome o The study was activated in December 2013. Target accrual is 338 patients, which is expected to be complete on time in March 2018.  BMT CTN 1304 / DFCI 10-106 / IFM/DFCI 2009 (The DETERMINATION Study): A randomized Phase III study comparing conventional dose treatment using a combination of lenalidomide, bortezomib, and dexamethasone to high-dose treatment with peripheral stem cell transplant in the initial management of myeloma in patients up to 65 years of age o This study is a collaboration between the DFCI and IFM with DFCI coordinating the study in the US and IFM in France. DFCI activated the study in October 2010. Slow accrual led the DFCI group to request BMT CTN endorsement. The BMT CTN endorsed the study in November 2013 when accrual to the competing BMT CTN 0702 completed. Participating BMT CTN centers have received accrual credit since then, and the monthly accrual more than doubled. In October 2016, it was determined the sample size should be increased from 660 to 720 randomized patients as the event rate was lower than anticipated and, therefore, there was insufficient power to detect the targeted difference between the study arms. The amended protocol was released to centers in November 2016. Accrual slowed considerably as IRB approval was required for continued enrollment. It is anticipated accrual will complete in 2017.

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 6.0 Future Directions

 UT RECRUIT / BMT CTN 1505. A Randomized Recruitment Intervention Trial o The RECRUIT study is conducted by Dr. Barbara Tilley, a PhD statistician at the University of Texas Health Science Center at Houston. The study is funded by a National Institute on Minority Health and Health Disparities grant, and the grant allows for collaboration among other NIH- funded networks / groups. The study was activated in April 2015. Participating centers were randomized into one of two arms: intervention or control, with the center investigators and coordinators enrolled as the research subjects. The study is slated to close in Spring 2017 at the end of the two-year study period. 6.3.3 Studies Activated Four studies were activated during this reporting period:  BMT CTN 1201 / Alliance A051301: Phase III Study of ibrutinib during and following autologous HCT vs. placebo in patients with relapsed / refractory DLBCL of the activated-B-cell subtype o Initially approved by BMT CTN in January 2012, this protocol was transferred to the National Clinical Trials Network to take advantage of NCI’s CRADA for ibrutinib, with Alliance serving as the lead group. The protocol was reviewed by NCI’s Cancer Therapy Evaluation Program and the FDA in late 2015. The protocol was released to centers and activated in July 2016. Target accrual is 302 patients over 48 months; as of March 31, 2017, 3 patients were enrolled.  BMT CTN 1401: Phase II multicenter trial of single autologous hematopoietic cell transplant followed by lenalidomide maintenance for multiple myeloma with or without vaccination with dendritic cell / myeloma fusions o The protocol team was formed in April 2014. The protocol was approved by the Protocol Review Committee in December 2014 and Data and Safety Monitoring Board in February 2015. The IND was approved by the FDA in October 2015. The protocol was released to centers in January 2016 and activated in July 2016. The estimated target enrollment is 188 patients (for final accrual of 132 patients) over 36 months; as of March 31, 2017, 33 patients were enrolled.  BMT CTN 1501: Randomized, Phase II, multi-center, open label study comparing sirolimus to prednisone in patients with refined Minnesota standard risk, Ann Arbor 1/2 confirmed acute GVHD o The protocol team held its first meeting in February 2015. The protocol was approved by the Protocol Review Committee in December 2015 and Data and Safety Monitoring Board in February 2016. It was released to centers in April 2016 and activated in October 2016. The estimated target enrollment is 150 patients (for final accrual of 120 patients) over 24 months; as of March 31, 2017, 25 patients were enrolled.  BMT CTN 1503: STRIDE2: A study to compare bone marrow transplantation to standard care in adolescents and young adults with severe sickle cell disease o The protocol team held its first meeting in July 2015. The protocol was approved by the Protocol Review Committee in December 2015 and Data and Safety Monitoring Board in April 2016. It was released to centers in May 2016 and activated in November 2016. The estimated target enrollment is 200 patients (for final accrual of 60 patients to donor arm) over 36 months; as of March 31, 2017, 3 patients were enrolled.

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 6.0 Future Directions 6.3.4 Studies to be Activated Five protocols will be activated during the next reporting period:  BMT CTN 1502: Optimizing cord blood and haploidentical aplastic anemia transplantation (CHAMP) o The protocol team held its first meeting in January 2015. The protocol was approved by the Protocol Review Committee in December 2015 and the Data and Safety Monitoring Board in October 2016. The protocol was released to centers in December 2016 and is anticipated to be activated in April 2017.  BMT CTN 1506: Multi-center, randomized, double-blind, placebo-controlled Phase III trial of the FLT3 inhibitor gilteritinib administered as maintenance therapy following allogeneic HCT for patients with FLT3 / ITD AML o The protocol team held its first meeting in July 2015. The protocol was approved by the Protocol Review Committee in February 2016. It was initially approved by the Data and Safety Monitoring Board in April 2016 with subsequent approval for amendments in September 2016. The protocol was released to centers in March 2017 and is expected to be activated in May 2017.  BMT CTN 1507: Reduced intensity conditioning for haploidentical bone marrow transplantation in patients with symptomatic sickle cell disease o The protocol team held its first meeting in July 2015. The protocol was approved by the Protocol Review Committee in April 2016 and the Data and Safety Monitoring Board in April 2017. It is anticipated the protocol will be released to centers in May 2017 and activated in August 2017.  ECOG EA4151 / BMT CTN 1601: A randomized Phase III trial of consolidation with autologous hematopoietic cell transplantation followed by maintenance rituximab vs. maintenance rituximab alone for patients with mantle cell lymphoma in minimal residual disease-negative first complete remission o The National Clinical Trials Network is leading this study with ECOG/ACRIN serving as the lead group. The proposal was initially presented to the BMT CTN Steering Committee in December 2015 after initial study synopsis development by the ECOG mantle cell lymphoma subcommittee. Feedback was also sought at the February 2016 Steering Committee meeting, and the protocol was officially endorsed by the BMT CTN Steering Committee at the June 2016 meeting. The protocol was approved by NCI Lymphoma Steering Committee in March 2016 and the NCI’s Cancer Therapy Evaluation Program and the NCI Central IRB in January 2017. The protocol is slated to be released to centers and activated in June 2017.  BMT CTN 1602. A Phase II, randomized, double-blind, placebo-controlled, study evaluating treatment of high risk acute graft-versus-host disease with filgotinib and corticosteroids o The protocol team held its first meeting in September 2016. The protocol was approved by the Protocol Review Committee in February 2017. It will be submitted to the Data and Safety Monitoring Board in May. Protocol release is slated for Summer 2017. 6.3.5 Future Study Concepts As noted in Section 6.1, future study concepts will be evaluated at the June 2107 Steering Committee meeting. In preparation for the next grant period, no additional concepts for BMT CTN-led studies were approved after September 2016.

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 6.0 Future Directions 6.4 Conclusions The BMT CTN has created a successful and efficient infrastructure for conducting important HCT trials. Network trials address critical issues in optimal graft sources, conditioning intensity, regimen-related toxicity, engraftment, GVHD, infection, disease control, and quality of life. Because of its comprehensive portfolio and successful accrual, the Network is recognized as the leading group to facilitate and complete clinical studies addressing HCT issues. This is clearly evidenced by successful collaborations with affiliate transplant centers, NIH National Clinical Trials Network, the Cancer Trials Support Unit, other consortia and research networks, and the increasing number of investigators and groups seeking partnerships with the Network. The availability of an effective network for transplant trials has also led to greater interest on the part of pharmaceutical and device companies to invest in transplant indications and to consider public-private partnerships that advance the field’s scientific agenda. While multicenter trials pose logistical and scientific challenges beyond those of a single-center study, they also address questions unanswerable in single institutions. Both large Phase II and Phase III approaches bring the strength of broader multi-institutional enrollment to confirm, amplify, or clarify conclusions from prior, more limited pilot studies. The HCT community understands that innovative and multi-institutional trials are needed to address the hardest questions facing patients with life-threatening hematopoietic diseases and are enthusiastic about the opportunities to conduct these trials through the Network. The BMT CTN plays a crucial role in advancing the field of HCT in a variety of ways. The most important is by providing the infrastructure to conduct trials successfully and efficiently. However, the Network also makes its data and specimens available for ancillary and correlative studies, disseminates research results, and brings the community together to determine future research needs. Through involvement of more than 100 transplant centers, BMT CTN trials have accrued almost 9,500 patients in a timely manner. Of the 42 studies opened, 31 are complete. The Network is committed to sharing the results of these trials in HCT, hematology, oncology, and medical peer- reviewed journals as well as at scientific meetings. To date, the BMT CTN has published and shared more than 150 manuscripts and presentations, including 15 manuscripts (5 of primary study results) and 15 presentations during this reporting period. The Network works together with the CIBMTR and ASBMT to publicize results and activities at the annual BMT Tandem Meetings where it has a prominent place in the meeting agenda organizing sessions for investigators and for clinical research staff. Additionally, the BMT CTN collaborates with leaders throughout the fields of hematology and oncology to survey the HCT landscape to determine future research directions through periodic State of the Science Symposia, which lay out an agenda for multicenter trials to have the maximal impact on improving health of patients facing life-threatening and/or debilitating blood diseases. The DCC and the Network’s Core and Affiliate Centers represent the highest level of commitment and participation by patients, researchers, transplant center staff, and support personnel – all working together in this valuable endeavor to achieve the BMT CTN’s original mission: to improve the outcomes of HCT for patients with life-threatening disorders.

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 6.0 Future Directions

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.1 Protocols Open to Accrual 7.0 Protocol Descriptions

The following section describes each BMT CTN research study. Accrual graphs, included as appropriate, are based on the period from study inception through March 31, 2017. Reporting period updates are highlighted in bold font. Protocols are grouped by study development stage:  Open to accrual and actively accruing patients (11)  Completed accrual during this reporting period (3)  Completed accrual during a previous reporting period (28)  Released to centers (2) 7.1 Protocols Open to Accrual BMT CTN Protocols Open to Accrual (as of March 31, 2017) BMT CTN Protocol Title Protocol # 07LT Continued, long-term follow-up and lenalidomide maintenance therapy for patients who have enrolled on BMT CTN 0702 1101 A multi-center, Phase III, randomized trial of reduced intensity conditioning and transplantation of double unrelated umbilical cord blood versus HLA-haploidentical related bone marrow for patients with hematologic malignancies 1102 A multi-center biologic assignment trial comparing reduced intensity allogeneic hematopoietic cell transplant to hypomethylating therapy or best supportive care in patients aged 50-75 with intermediate-2 and high risk myelodysplastic syndrome 1201 / A randomized double-blind Phase III study of ibrutinib during and following autologous stem cell Alliance transplantation versus placebo in patients with relapsed or refractory diffuse large B cell A051301 lymphoma of the activated B cell subtype 1301 A randomized, multi-center, Phase III trial of calcineurin inhibitor-free interventions for prevention of graft-versus-host disease 1302 Multicenter Phase II, double-blind placebo controlled trial of maintenance ixazomib after allogeneic hematopoietic stem cell transplantation for high risk multiple myeloma 1304 / A randomized Phase III study comparing conventional dose treatment using a combination of DFCI 10-106 / lenalidomide, bortezomib, and dexamethasone (RVD) to high-dose treatment with peripheral stem IFM/DFCI 2009 cell transplant in the initial management of myeloma in patients up to 65 years of age 1401 Phase II multicenter trial of single autologous hematopoietic cell transplant followed by lenalidomide maintenance for multiple myeloma with or without vaccination with dendritic cell / myeloma fusions 1501 A randomized, Phase II, multicenter, open label, study evaluating sirolimus and prednisone in patients with refined Minnesota standard risk, Ann Arbor 1/2 confirmed acute graft-versus-host disease 1503 A study to compare bone marrow transplantation to standard care in adolescents and young adults with severe sickle cell disease 1505 / A randomized recruitment intervention trial (RECRUIT) UT RECRUIT

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.1 Protocols Open to Accrual

BMT CTN 07LT

Protocol Number: BMT CTN 07LT Continued, long-term follow-up and lenalidomide maintenance therapy for patients who have enrolled Title: on BMT CTN 0702 Therapeutic advances in multiple myeloma have resulted in substantially improved survival. In a large population-based study of 45,595 multiple myeloma patients, myeloma-specific 5-year median overall survival improved from 36% to 68% under age 50, and from 34% to 58% among patients of ages 51-65 in the years between 1973 and 2009. Post-transplant consolidation and maintenance strategies have also yielded improved progression-free and overall survival. The BMT CTN 0702 study randomized patients to receive two autologous HCTs, one autologous HCT and post-transplant consolidation, or one autologous HCT with maintenance. Of Rationale: note, all patients receive a total of 3 years of maintenance therapy using lenalidomide. Since the implementation of BMT CTN 0702, the experience with maintenance has broadened, and at least two large Phase III clinical trials that continued lenalidomide maintenance for longer periods were associated with longer survival compared to placebo. This long-term follow-up protocol focuses on extending the follow-up period for all patients on BMT CTN 0702 to assess long-term outcomes, such as progression-free survival and incidence of second primary malignancies. A secondary objective is to provide patients with lenalidomide maintenance therapy free of charge until there is evidence of disease progression. To compare progression-free survival as a time to event analysis between the three randomized treatment arms from the BMT CTN 0702 protocol as a pairwise comparison. The analysis will be Primary Objective: conducted once all surviving patients have been followed for at least 5 years post randomization on the BMT CTN 0702 protocol. To examine the cumulative incidence of second primary malignancies, probability of overall survival, Secondary Objectives: probability of event-free survival, and health quality of life on all patients, including those not receiving long-term lenalidomide maintenance therapy. Team Principals: Name Email Amrita Krishnan [email protected] Chairs: George Somlo [email protected] Edward Stadtmauer [email protected] Officer: Marcelo Pasquini [email protected] Coordinator: Brianne Allison [email protected] Medical Monitor: Shannon Smiley [email protected] Statistician: Nancy Geller [email protected] Contract Rep: Nancy Poland [email protected] Additional Members: Email PRC Approval Date: 06/10/2014 Angela Dispenzieri [email protected] DSMB Approval Date: 07/30/2014 Sergio Giralt [email protected] Opened to Accrual: 03/04/2015 John Koreth [email protected] Closed to Accrual: N/A Adam Mendizabal [email protected] Target Accrual: 450 patients Philip McCarthy [email protected] Total Accrual as of 3/31/2017: 240 patients Courtney Nelson [email protected] Reporting Period Accrual: 110 patients Hari Parameswaran [email protected] IND Number: 104912 Muzaffar Qazilbash [email protected] Recent Version Released: 04/28/2016 David Vesole [email protected]

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.1 Protocols Open to Accrual

Protocol Number: BMT CTN 07LT In November 2013, a proposal was submitted to the Steering Committee to amend the BMT CTN 0702 protocol to continue lenalidomide maintenance therapy until progression based on recent data from two major clinical trials, including BMT CTN 0704 / CALGB 100104. The Steering Committee elected to Key Highlights: implement BMT CTN 07LT as a separate protocol instead of an amendment to 0702 in order to reduce the impact on the 0702 primary endpoint and to provide patients with the option to withdraw from long-term maintenance or follow up. From a regulatory standpoint, a separate protocol also provides the opportunity to finish, close, and conduct analyses on 0702 before all patients progress. Of the 55 centers that accrued on 0702, 12 declined to participate on 07LT. There are 42 sites activated on the 07LT protocol and one center pending activation in the next reporting period. It was anticipated that approximately 450 patients would be eligible to enroll on this protocol based on assumed estimates of progression-free survival from the 0702 study; however, the final accrual will be dependent on the observed rate of progression-free survival on the 0702 study. Accrual continues Reporting Period behind projections due to a multitude of factors, including slower than anticipated center activation, Update: consent timing logistics due to time between and location of 0702 patient follow up visits, patient refusal, and patients lost-to-follow-up. To promote accrual, emails were sent to remind sites of upcoming eligible patients to approach for participation. An updated protocol v2 was released to centers on April 28, 2016; it included modifications and clarifications to adverse event reporting requirements.

BMT CTN 07LT Target accrual = 450 patients

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.1 Protocols Open to Accrual BMT CTN 1101

Protocol Number: BMT CTN 1101 A multi-center, Phase III, randomized trial of reduced intensity conditioning and transplantation of Title: double unrelated umbilical cord blood versus HLA-haploidentical related bone marrow for patients with hematologic malignancies Reduced intensity conditioning (RIC) HCT has allowed older and less clinically fit patients to receive potentially curative treatment with allogeneic HCT for high risk or advanced hematological malignancies. Patients lacking an HLA-matched sibling may receive a graft from a suitably HLA-matched unrelated donor. However, up to a third of patients will not have an HLA-matched sibling or a suitably matched adult unrelated donor. Even when a suitably matched unrelated donor is identified, data from NMDP/Be The Match indicate that a median of four months is required to complete searches that result in transplantation; thus, some number of patients succumb to their disease while awaiting identification and evaluation of a suitably matched adult unrelated donor. Single or dual center studies showed partially HLA-mismatched related bone marrow and unrelated double umbilical cord blood are Rationale: valuable sources of donor cells for RIC HCT, extending this treatment modality to patients who lack other donors. To study the reproducibility, BMT CTN conducted two parallel prospective Phase II clinical trials. These two studies evaluated the safety and efficacy of related haplo-bone marrow (BMT CTN 0603) and double umbilical cord blood (BMT CTN 0604) transplantation after RIC. Both alternative donor approaches produced early results similar to that reported with unrelated donor, and even HLA- matched sibling, BMT. These data demonstrate not only the efficacy of both approaches but also that both can be safely exported from the single center setting. Both haplo-bone marrow and double umbilical cord blood grafts can be obtained rapidly for >90% of patients lacking an HLA-matched donor. In addition to the primary protocol, the 1101 study includes a companion Cost-Effectiveness protocol, which evaluates the cost differences between the two 1101 study arms. To compare progression-free-survival at two years between patients who receive unrelated double cord blood unit versus HLA haploidentical related bone marrow transplantation. Cost-Effectiveness: To Primary Objective: determine the cost-effectiveness between these two transplantation methodologies expressed as the cost per quality adjusted life year. To evaluate neutrophil recovery, graft failure, platelet recovery, donor cell engraftment, acute and chronic GVHD, overall survival, treatment-related mortality, infections, hospital admission and length of Secondary Objectives: stay, health related quality of life, and relapse / progression. Cost-Effectiveness: To examine out-of- pocket costs, the cost of informal caregiving, and the impact on workplace productivity, for both patients and caregivers. Team Principals: Name Email PRC Approval Date: 10/22/2011 Claudio Brunstein [email protected] DSMB Approval Date: 01/09/2012 Chairs: Ephraim Fuchs [email protected] Opened to Accrual: 6/19/2012 Paul O’Donnell [email protected] Closed to Accrual: N/A Officer: Mary Eapen [email protected] Target Accrual: 410 patients Coordinator: Jamie Garrison [email protected] Total Accrual as of 03/31/17: 313 patients Medical Monitor: Gabrielle Meyers [email protected] Reporting Period Accrual: 77 patients Statistician: Brent Logan [email protected] IND Number: N/A Contract Rep: Pam Budnick [email protected] Recent Version Released: 01/20/2017 Additional Members: Email Additional Members: Email Omar Aljitawi [email protected] Nancy DiFronzo [email protected] Joe Antin [email protected] Mary Horowitz [email protected] Karen Ballen [email protected] Chatchada Karanes [email protected] Javier Bolaños-Meade [email protected] Elizabeth Rich [email protected]

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.1 Protocols Open to Accrual

Protocol Number: BMT CTN 1101 Luciano Costa [email protected] Liz Wagner [email protected] Corey Cutler [email protected] John Wingard [email protected] Steve Devine [email protected] BMT CTN 1101 is a Phase III randomized follow-on study to the Phase II 0603 (haplo bone marrow) and the 0604 (double umbilical cord blood) studies. The protocol was approved by the PRC in October 2011 and DSMB in January 2012. Version 1 of the protocol was released to centers in February 2012. The study was opened to accrual in June 2012. The Cost-Effectiveness Companion study protocol was released in November 2012. The study has continually struggled to meet accrual targets. In addition to Key Highlights: revising the restrictive eligibility criteria through several amendments, the protocol team identified challenging issues hampering accrual, including referring and transplant physician bias and competing protocols. Accrual initiatives to address these barriers included the development of educational material explaining the trial and donor choices, site visits from the study chairs to interested centers, and routine email communication to 1101 site PIs and coordinators. Version 8 of the protocol was released in January 2017, further clarifying the eligibility criteria. Accrual continues to be a challenge for the study; however, with the addition of new sites and Reporting Period promotion from the protocol team, the study achieved 88% of the target enrollment for the Update: reporting period. The study team continues to work with sites to identify barriers and address institutional biases. Accrual is anticipated to complete in Spring 2018. 1. Design of a cost-effectiveness analysis alongside a randomized trial of transplantation using UCB versus HLA-haploidentical related bone marrow in advanced hematologic cancer. Journal of Comparative Effectiveness Research. 2014 Mar 1; 3(2):135-144. Publications: 2. Donor selection recommendations (including 0603 / 0604 long term follow-up data): Mismatched related and unrelated donors for allogeneic HCT for adults with hematologic malignancies. Biology of Blood and Marrow Transplantation. 2014 Oct 1; 20(10):1485-1492. Epub 2014 May 23.

BMT CTN 1101 Target accrual = 410 patients

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.1 Protocols Open to Accrual BMT CTN 1102

Protocol Number: BMT CTN 1102 A multi-center biologic assignment trial comparing reduced intensity allogeneic hematopoietic cell Title: transplant to hypomethylating therapy or best supportive care in patients aged 50-75 with intermediate-2 and high risk myelodysplastic syndrome Advances in both the understanding of MDS and in the development of alternatives to standard leukemia induction therapy in the treatment of MDS, including hypomethylating therapy and RIC allogeneic HCT for older patients, lead to questions about the appropriate role and timing of these therapies. This trial will compare RIC allogeneic HCT with hypomethylating / best supportive care in patients with higher risk MDS who are referred for transplantation evaluation. The study is consistent with the National Comprehensive Cancer Center Treatment Guidelines for MDS and with suggestions from a recent review article by Giralt et al. regarding clinical trials to provide Rationale: evidence for Medicare coverage of allogeneic transplant for MDS. The design will use assignment to transplantation when a donor is available or best supportive care (usually hypomethylating therapy) when a suitable matched related or unrelated donor is not available. Patients with an HLA-matched sibling or unrelated donor will proceed to allogeneic transplantation utilizing an institutionally-approved RIC regimen. Patients without a suitable donor will be offered hypomethylating therapy (or other best supportive care). The primary objective is to determine whether there is a meaningful benefit (overall survival advantage) among those who undergo RIC allogeneic HCT when compared to those who continue hypomethylating therapy / best supportive care. To compare the three-year overall survival probabilities between RIC allogeneic HCT and non-transplant Primary Objective: therapy / best supportive care using an intent-to-treat analysis. To compare leukemia-free survival at 3 years from enrollment and quality of life measures between Secondary Objectives: treatment arms. Team Principals: Name Email PRC Approval Date: 01/24/2013 Corey Cutler [email protected] DSMB Approval Date: 05/02/2013 Chairs: Ryo Nakamura [email protected] Opened to Accrual: 12/16/2013 Officer: Wael Saber [email protected] Closed to Accrual: N/A Coordinator: Alyssa Ramirez [email protected] Target Accrual: 338-400 pts Medical Monitor: Bipin Savani [email protected] Total Accrual as of 03/31/17: 248 patients Statistician: Raphael Fraser [email protected] Reporting Period Accrual: 83 patients Contract Rep: Nancy Poland [email protected] IND Number: N/A Additional Members: Email Recent Version Released: 07/02/2015 Fred Appelbaum [email protected] Additional Members: Email Joseph Alvarnas [email protected] Bill Merritt [email protected] Richard Champlin [email protected] Betul Oran [email protected] Dennis Confer [email protected] Joycelynne Palmer [email protected] Nancy DiFronzo [email protected] Marcelo Pasquini [email protected] Steve Forman [email protected] Scott Ramsey [email protected] Steven D. Gore [email protected] Bart Scott [email protected] Mary Horowitz [email protected] Mikkael Sekeres [email protected] Eric Leifer [email protected] Richard Stone [email protected] Brent Logan [email protected] Roni Tamari [email protected] Adam Mendizabal [email protected] The protocol was approved by the PRC in January 2013 and DSMB in May 2013. Version 1.0 was Key Highlights: released to centers for local IRB submission in August 2013. The study was activated for enrollment on December 16, 2013, after several centers received IRB approval. Twenty-Eight Core Centers and 8

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.1 Protocols Open to Accrual

Protocol Number: BMT CTN 1102 Affiliate Centers are activated for enrollment. Version 2.0 of the protocol was released to centers in July 2014. This amendment updated the eligibility requirements to state the unrelated donor search may begin once a patient consents, and the bone marrow aspirate may be within 30 days prior to consent instead of 30 days prior to enrollment. There was also a list of acceptable MDS subtypes added to the eligibility criteria. A Segment 0 enrollment staging area was added to capture patients who have consented but do not have a recent bone marrow biopsy. Lastly, the informed consent was updated to include more information about the different treatment options for MDS and to include more information about the risks associated with hypomethylating therapy, RIC, and transplant. Version 3.0 of the protocol was released to centers in December 2014.The brief amendment updated the eligibility requirements to state the bone marrow aspirate could be performed within 60 days prior to consent instead of 30 days. This timeframe had been identified as one of the most common accrual barriers, and after the amendment was implemented, accrual increased. The start of the unrelated donor search was also clarified to be at the time samples are requested from potential NMDP/Be The Match donors. Version 4.0 of the protocol was released to centers in July 2015. This amendment incorporated the Ancillary Cost-Effectiveness Analysis Protocol as an appendix to the study and added information regarding objectives, endpoints, and data for this ancillary study. Reporting Period Accrual has continued at a steady rate of 95-100% of projections. As of February, accrual was 75% Update: complete. The protocol is expected to complete accrual in March 2018. 1. Treatment of older patients with high-risk MDS: The emerging role of allogeneic HCT. Current Hematologic Malignancy Reports. 2014 Mar 1; 9(1):57-65.

Publications: 2. Multicenter biologic assignment trial comparing reduced-intensity allogeneic HCT to hypomethylating therapy or best supportive care in patients aged 50 to 75 with intermediate-2 and high-risk MDS: BMT CTN #1102 study rationale, design, and methods. Biology of Blood and Marrow Transplantation. 2014 Oct 1; 20(10):1566-1572. Epub 2014 Jun 24.

BMT CTN 1102 Target accrual = 400 patients

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.1 Protocols Open to Accrual BMT CTN 1201 / Alliance A051301

Protocol Number: BMT CTN 1201 / Alliance A051301 A randomized double-blind Phase III study of ibrutinib during and following autologous stem cell Title: transplantation versus placebo in patients with relapsed or refractory diffuse large B cell lymphoma of the activated B cell subtype DLBCL is the most common lymphoma worldwide. Even though rituximab / anthracycline-containing chemotherapy (e.g. R-CHOP) can cure a significant proportion of patients with this disease in the modern era, approximately 40% are either refractory to front-line treatment or relapse following therapy. Gene expression profiling has identified two distinct subtypes of DLBCL with a differential response to front-line chemotherapy: germinal center B cell-like and activated B cell-like (ABC), which have dramatically different 5-year survival rates of 60% versus 35% after CHOP, respectively. At the time of relapse, regardless of disease subtype, the standard of care involves salvage chemotherapy followed by autologous HCT in chemosensitive patients. With this approach, 24-month progression- free survival following transplantation in the rituximab era approaches 48% and 24-month overall survival 65%. Disease progression or relapse following autologous HCT is the major cause of mortality in this patient population. Most relapses (~70%) occur in the first 12 months following autologous HCT. The current study was thus designed to improve survival outcomes in this patient population by incorporating biologically targeted therapy in the treatment program. Rationale: Patients with relapsed DLBCL in the rituximab era have poor outcomes with conventional standard approaches to autologous HCT. Additionally, patients with the ABC subtype of DLBCL as defined by either mRNA or protein methods have proven inferior outcomes in the front-line setting with standard chemotherapy approaches and differential response to salvage therapies in the relapsed / refractory setting. Ibrutinib is a selective inhibitor of Bruton’s tyrosine kinase (BTK), a critical component of the chronic active B cell receptor (BCR) signaling pathway, which plays a central role in the pathogenesis of ABC DLBCL. Our hypothesis is that the addition of ibrutinib, which as a single agent is clinically active in the relapsed / refractory setting of ABC DLBCL, will augment transplant effectiveness and target residual low-burden disease thus leading to an improvement in 24-month progression-free and overall survival in this patient population. This is a randomized placebo-controlled Phase III study that will evaluate ibrutinib therapy during and following autologous HCT in this high-risk patient population. This approach is novel in selectively targeting the ABC subtype of disease using a biologically relevant small molecule inhibitor in combination with high-dose therapy. To compare progression-free survival at two years between patients who receive ibrutinib during and Primary Objective: following autologous HCT versus those who receive placebo during and following autologous HCT. To evaluate overall survival, post-transplant response rates, hematopoietic recovery, safety and Secondary Objectives: tolerability of ibrutinib, secondary malignancies, and immune reconstitution. Team Principals: Charalambos Babis Andreadis PRC Approval Date: N/A [email protected] DSMB Approval Date: N/A Chairs: Timothy Fenske (BMT CTN) Opened to Accrual: 07/06/2016 [email protected] Closed to Accrual: N/A Officer: Alliance Target Accrual: 302 patients Coordinator: Alliance Total Accrual as of 3/31/2017: 3 patients Medical Monitor: Alliance Reporting Period Accrual: 3 patients Statistician: Alliance IND Number: CTEP Contract Rep: Alliance Recent Version Released: 11/22/2016

Key Highlights: Initially approved by the BMT CTN in January 2012, this protocol was transferred later that year to the Natioanl Clinical Trials Network to take advantage of NCI’s CRADA for ibrutinib, with Alliance serving as

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.1 Protocols Open to Accrual

Protocol Number: BMT CTN 1201 / Alliance A051301 the lead group. After multiple revisions, the protocol was approved by the NCI Lymphoma Steering Committee in November 2014. The protocol was further revised as a registration trial and was reviewed by NCI’s Cancer Therapy Evaluation Program and the FDA in late 2015. The protocol was activated in July 2016. The BMT CTN DCC contacted Core and Consortia Center investigators announcing the activation, providing contact information regarding how to open the Reporting Period study via the NCI’s Clinical Trials Support Unit, and reminding that BMT CTN accrual credit will be Update: provided in addition to National Clinical Trial Network accrual credit. Subsequent communications to BMT CTN centers have been made via email and Steering Committee presentations, including activation updates and workflow logistics recommendations.

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.1 Protocols Open to Accrual BMT CTN 1301

Protocol Number: BMT CTN 1301

Title: A randomized, multi-center, Phase III trial of calcineurin inhibitor-free interventions for prevention of graft-versus-host disease Chronic GVHD is a devastating complication that affects HCT survivors and may offset the associated benefits of reducing rates of post-transplant disease relapse. The combination of calcineurin inhibitors (tacrolimus and cyclosporine A) with methotrexate is the most common GVHD prophylaxis used worldwide in the context of myeloablative conditioning transplants. This regimen, implemented more than three decades ago, demonstrated better control of acute GVHD. However, this strategy is ineffective against chronic GVHD. Management of chronic GVHD remains a challenge and it has become a significant health problem in transplant survivors with more frequent use of mobilized PBSC. Additionally, several issues arise with this treatment approach: 1) methotrexate- accentuated risk of conditioning regimen-related oral mucositis and renal toxicity; 2) increased risk of Rationale: thrombotic microangiopathy due to calcineurin inhibitors; 3) requirement for chronic monitoring of calcineurin inhibitor serum levels; and 4) chronic immunosuppression is not a conducive platform for post-HCT cellular therapies for treatment or prevention of infections or disease relapse. In vivo graft manipulation with anti thymocyte globulin or alemtuzumab, ex vivo graft manipulation with CD34 selection and T-cell depletion, and, most recently, use of high doses of cyclophosphamide after transplant are strategies that are associated with lower rates of chronic GVHD. In addition, a benchmark analysis of novel approaches to prevent GVHD using data from the CIBMTR identified two strategies for T-cell depletion, using either CD34-selection or administration of post-transplantation cyclophosphamide, as the most effective in preventing both acute and chronic GVHD after HCT. This clinical trial further explores these approaches to prevent chronic GVHD which have the additional benefit of not requiring prolonged immunosuppression. To compare chronic GVHD / relapse-free survival as a time to event endpoint after hematopoietic stem Primary Objective: cell transplant between each of the calcineurin inhibitor-free interventions and a tacrolimus / methotrexate control. To compare rates of grade II-IV and III-IV acute GVHD, chronic GVHD, chronic GVHD-free survival, Secondary immunosuppression-free survival at one year, neutrophil and platelet engraftment, disease relapse, Objectives: transplant-related mortality (TRM), rates of Grade ≥3 toxicity; incidence of cytomegalovirus and Epstein- Barr virus reactivation, incidence of infections; immune reconstitution, quality of life, and overall survival. Team Principals: Name: Email: Leo Luznik [email protected] Chairs: Miguel Perales [email protected] Chair / Officer: Marcelo Pasquini [email protected] Coordinator: Kristy Applegate [email protected] Tamila Kindwall-Keller [email protected] Medical Monitors: Dianna Howard [email protected] Statistician: Brent Logan [email protected] Contract Rep: Pam Budnick [email protected] Additional Members: Email: PRC Approval Date: 12/17/2013 Steve Devine [email protected] DSMB Approval Date: 02/06/2014 Nancy DiFronzo [email protected] Opened to Accrual: 08/17/2015 Nancy Geller [email protected] Closed to Accrual: N/A Sergio Giralt [email protected] Target Accrual: 345 patients Helen Heslop [email protected] Total Accrual as of 3/31/17: 173

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.1 Protocols Open to Accrual

Protocol Number: BMT CTN 1301 Vincent Ho [email protected] Reporting Period Accrual: 140 Carolyn Keever-Taylor [email protected] IDE Number: 16059 Lauren Kunz [email protected] Recent Version Released: 07/15/2016 Adam Mendizabal [email protected] Additional Member: Email: Eneida Nemecek [email protected] Robert Soiffer [email protected] Lynn O’Donnell [email protected] Scott Solomon [email protected] The study was approved by the PRC in December 2013 and DSMB in February 2014.Version 1.0 of the protocol was released to centers for IRB submission in September 2014. The study was activated in August 2015 and is currently open to enrollment at 22 of 31 possible participating centers. A protocol version 2.0 amendment to the protocol was reviewed and approved by the DSMB in April Key Highlights: 2015. This amendment included a change to chemotherapy dose calculations; language clarifying that donors of patients randomized to the CD34 selection arm will be considered research subjects because their specimens will be processed through an investigational device; additional language regarding data submission, adverse event reporting, ethics, and regulatory requirements; and new donor informed consent and assent forms for donors of patients randomized to the CD34 selection arm. A protocol version 3.0 amendment was approved in June 2016 by the DSMB. This amendment included inclusion criterion for chronic myelomonocytic leukemia patients, specifications to exclude post-transplant maintenance therapy patients except for those receiving FLT3 or tyrosine kinase Reporting Period inhibitors, replacement of toxoplasmosis NAAT testing post-transplant with toxoplasmosis Update: prophylaxis at day 30 for at-risk patients on the CD34-selection arm, and expansion of the window from randomization to initiation of conditioning regimen from 28 days to as soon as possible. Accrual has been higher than anticipated with 173 patients enrolled to date when only 109 were projected.

BMT CTN 1301 Target accrual = 345 patients

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.1 Protocols Open to Accrual BMT CTN 1302

Protocol Number: BMT CTN 1302

Title: Multicenter Phase II, double-blind placebo controlled trial of maintenance ixazomib after allogeneic hematopoietic stem cell transplantation for high risk multiple myeloma The treatment outcomes of high risk multiple myeloma patients remain suboptimal even in the era of novel agents and abundance of available regimens. There is considerable unmet need to improve their therapeutic outlook, and the role of allogeneic HCT in this population remains to be defined. The introduction of reduced intensity regimen has resulted in reduced TRM in allogeneic HCT for patients with myeloma. Emerging single center experience supports the feasibility of a RIC regimen of fludarabine, melphalan plus bortezomib in patients with multiple myeloma. However, myeloma relapse still needs to be reduced in order to maximize the efficiency of this therapeutic approach in high risk patients. This clinical trial addresses these two challenges with allogeneic HCT. First, addition of bortezomib to the conditioning regimen can optimize the anti-myeloma effect of melphalan against malignant plasma cells and bortezomib after the stem cell infusion is associated with lower rates of Rationale: severe acute GVHD. Second, the addition of a novel maintenance drug may further reduce the risk of disease relapse long enough for the graft versus myeloma to take effect. Given the small number of myeloma patients treated with an allogeneic HCT at individual institutions, we will perform a multicenter study evaluating the conditioning regimen of fludarabine, melphalan plus bortezomib followed by allogeneic HCT from a HLA-matched related or unrelated donor in patients with high risk multiple myeloma. Patients will be randomized to placebo-controlled maintenance therapy of ixazomib (MLN9708) after allografting, and the maintenance therapy will be prescribed for one year. The study will assess the novel conditioning regimen in high risk population as well as the efficacy of ixazomib in preventing disease relapse/progression following allogeneic HCT. The results of this trial will assist in understanding the role of this novel agent in post-allogeneic HCT maintenance and will assist in designing a definitive trial for this population with high risk multiple myeloma. To compare progression-free survival as a time to event endpoint from the time of randomization Primary Objective: between patients randomized to ixazomib versus placebo maintenance in patients with high risk multiple myeloma. To describe for each treatment arm: rates of grade II-IV and III-IV GVHD, chronic GVHD, best disease Secondary response rates, disease progression, transplant related mortality, overall survival, rates of Grade ≥ 3 Objectives: toxicity according to Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0, incidence of infections, and health-related quality of life. Team Principals: Name: Email: Qaiser Bashir [email protected] Chairs: Parameswaran Hari [email protected] Taiga Nishihori [email protected] Officer: Marcelo Pasquini [email protected] Coordinator: Samantha Wilkins [email protected] Medical Monitor: Dianna Howard [email protected] Statistician: Peter Dawson [email protected] Contract Rep: Kiila Lee [email protected] Additional Members: Email: PRC Approval Date: 02/04/2014 Melissa Alsina [email protected] DSMB Approval Date: 07/30/2014 Claudio Anasetti [email protected] Opened to Accrual: 08/17/2015 Yvonne Efebera [email protected] Closed to Accrual: N/A Cristina Gasparetto [email protected] Target Accrual: 138 Nancy Geller [email protected] Total Accrual as of 3/31/17: 22

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.1 Protocols Open to Accrual

Protocol Number: BMT CTN 1302 Sergio Giralt [email protected] Reporting Period Accrual: 5 John Koreth [email protected] IDE Number: 124415 Phil McCarthy [email protected] Recent Version Released: 10/18/2016 Emma Scott [email protected] Additional Member: Email: Edward Stadtmauer [email protected] David Vesole [email protected] The accrual period is 36 months, and patients will be followed for two years after transplant. The protocol was approved by the PRC in February 2014, DSMB in July 2014, and FDA in November 2014. Version 1.0 of the protocol was released to centers in March 2015. Twenty-nine centers are Key Highlights: participating in the trial. The protocol was opened to enrollment in August 2015. In March 2016, accrual was halted due to a higher than expected occurrence of neurologic toxicities within 100 days post-transplant. The unexpected occurrence of toxicities observed on the trial was reviewed by the protocol team, DSMB, and NHLBI over the course of several months. The FDA was informed in, and they placed a Reporting Period partial clinical hold on the study. The protocol’s conditioning regimen was modified in an amendment Update: to reduce the doses of study drug, and the accrual timeline was adjusted to account for the enrollment freeze. Protocol version 2.0 was approved by the DSMB in June 2016 and FDA in October 2016; it was released to centers in October 2016. Accrual resumed in November 2016, and five patients have enrolled since the study was reopened.

BMT CTN 1302 Target accrual = 138 patients

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.1 Protocols Open to Accrual BMT CTN 1304 / DFCI 10-106 / IFM/DFCI 2009 (The DETERMINATION Study)

Protocol Number: BMT CTN 1304 / DFCI 10-106 / IFM/DFCI 2009 (The DETERMINATION Study) A randomized Phase III study comparing conventional dose treatment using a combination of lenalidomide, Title: bortezomib, and dexamethasone (RVD) to high-dose treatment with peripheral stem cell transplant in the initial management of myeloma in patients up to 65 years of age For 15 years, high-dose therapy followed by autologous PBSC transplant has been the standard treatment for multiple myeloma in younger patients. For the last four or five years, the arrival of novel therapies (thalidomide, bortezomib, and lenalidomide) has revolutionized conventional therapeutic regimens. The Rationale: use of these new therapies has improved complete response and very good partial response rates of high- dose therapy, as well as those of conventional-dose therapy, to such a point that these rates have now become similar in both groups of treatment. Thus, the arrival of novel therapies has brought into question the necessity of high-dose therapy as first-line therapy in young patients. To compare progression-free survival between conventional-dose treatment and high-dose therapy plus Primary Objective: autologous PBSC transplant when both treatment arms receive novel drugs as part of induction, consolidation, and maintenance. To compare the response rates, time to progression, overall survival, toxicity, and quality of life between Secondary the two arms; define genetic prognostic groups evaluated by gene expression profiling; examine the best Objectives: treatment in each Gene Expression Profile-defined prognostic group; and collect medical resource utilization information which may be used in economic evaluation models. Team Principals: Name: Email: PRC Approval Date: DFCI Marcelo Pasquini (BMT CTN) [email protected] DSMB Approval Date: DFCI Chairs: paul_richardson@ DFCI: 10/2010 Paul Richardson (DFCI) Opened to Accrual: dfci.harvard.edu BMT CTN: 11/16/13 Officer: DFCI Closed to Accrual: N/A Amy Foley (BMT CTN) [email protected] Target Accrual: 720 patients Coordinators: andreaa_zeytoonjian@ Total Accrual as of Andrea Zeytoonjian 691 patients dfci.harvard.edu 3/31/17: Medical Monitor: DFCI Reporting Period Accrual: 92 patients Statistician: DFCI IND Number: Held by DFCI Contract Rep: DFCI This study is a collaboration between the DFCI and IFM with DFCI serving as the coordinating center for the US and the IFM coordinating the study in France. The French accrual (700 patients) is complete. The DFCI opened the study in October of 2010. Slower-than-anticipated accrual led the DFCI group to request BMT CTN endorsement of the study. The study was presented to the BMT CTN Steering Committee in February 2013, and the Committee agreed the BMT CTN would endorse the study and provide accrual credit for participating centers when the BMT CTN 0702 myeloma study completed accrual. The BMT CTN Myeloma Intergroup agreed with this plan and indicated 1304 would be the Network’s top priority myeloma study after BMT CTN 0702 closed. Key Highlights: BMT CTN 0702 participating centers were invited to participate on the 1304 study in June 2013 and complete activation requirements during the final months of 0702 accrual. The 0702 study closed to accrual on November 15, 2013, and centers were informed 1304 accrual credit would be provided as of the following day. To ease confusion about the multiple collaborators and study numbers, the study acronym of DETERMINATION (Delayed versus Early Transplant with Revlimid Maintenance and Antimyeloma Triple Therapy) was also created and is used on all study communications. The IFM study results were presented during the 2015 ASH Annual Meeting, showing a progression-free survival benefit at 3 years post-randomization. There was no statistically significant difference in overall survival. A key difference of the DETERMINATION study is that lenalidomide maintenance therapy is given

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.1 Protocols Open to Accrual

Protocol Number: BMT CTN 1304 / DFCI 10-106 / IFM/DFCI 2009 (The DETERMINATION Study) until disease progression whereas in the French study it was limited to one year post-transplant. There are 47 BMT CTN Core, Consortia, and Affiliate Centers activated on the study. BMT CTN centers have enrolled 443 patients since BMT CTN endorsement of the study in November 2013, including 88 this reporting period. Reporting Period In October, it was determined the sample size should be increased from 660 to 720 randomized patients. Update: Because the event rate was lower than anticipated, more patients were needed to provide sufficient power to detect the targeted difference between the study arms. The amended protocol was released to centers in November. Accrual slowed considerably as IRB approval was required for continued enrollment. Accrual is expected to complete in 2017.

This is a DFCI-led study, so a different type of accrual graph is provided. DFCI opened the trial to accrual in October 2010, and the BMT CTN endorsed it in November 2013.

BMT CTN 1304 / DFCI10-106 / IFM/DFCI 2009 (The DETERMINATION Study) 25

20 BMT CTN Endorsement

10 Patients Accruedper Month

2012-01 2012-11 2016-09 2010-12 2011-03 2011-05 2011-07 2011-09 2011-11 2012-03 2012-05 2012-07 2012-09 2013-01 2013-03 2013-05 2013-07 2013-09 2013-11 2014-01 2014-03 2014-05 2014-07 2014-09 2014-11 2015-01 2015-03 2015-05 2015-07 2015-09 2015-11 2016-01 2016-03 2016-05 2016-07 2016-11 2017-01 2017-03 2010-10

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.1 Protocols Open to Accrual BMT CTN 1401

Protocol Number: BMT CTN 1401

Title: Phase II multicenter trial of single autologous hematopoietic cell transplant followed by lenalidomide maintenance for multiple myeloma with or without vaccination with dendritic cell / myeloma fusions Multiple myeloma (MM) is associated with immune suppression, including defects in antigen presentation and effector cell function that are thought to play a role in disease progression. Although the outcomes for myeloma patients have improved greatly over the past decade, most patients relapse even after autologous stem cell transplant and post-transplant maintenance therapy with lenalidomide. This study assesses a tumor vaccine in which patient-derived myeloma cells are fused with autologous dendritic cells (DCs), such that a broad array of myeloma antigens is presented in the context of DC- mediated co-stimulation. Early phase clinical data demonstrate that post-transplant vaccination with a DC-MM fusion product with GM-CSF adjuvant increases the number of MM-specific T cells. Furthermore, it appears that lenalidomide can specifically augment vaccine-stimulated induction of MM-specific T cells. The study is therefore interested in combining standard immunomodulatory therapy (lenalidomide) with a potential immune stimulant (DC-MM vaccination) to increase post- transplant clinical response. Finally, pre-clinical data has suggested that immunomodulatory agents Rationale: augment natural killer cell activity and that natural killer cells interact with and can be activated by DCs. Thus this study will also assess the natural killer immunophenotype in the setting of post-transplant maintenance lenalidomide and the changes to this phenotype in the setting of DC-MM fusion vaccination. The study postulates that post-transplant lenalidomide maintenance will augment post-transplant antimyeloma immunity, thus providing an ideal platform for DC/MM fusion vaccination. Additionally, to understand the effect of vaccine versus the adjuvant in the post-transplant setting, the non-vaccine arms are split into lenalidomide alone and lenalidomide plus GM-CSF, with GM-CSF administered in the exact same schedule and dosing as in the vaccine arm. The results of this trial will provide information on whether this patient-specific vaccine administered after transplant is promising for further comparison with current standard of care treatment. Furthermore, this trial will address several important aspects of anti-myeloma immunity, including how lenalidomide maintenance influences post- transplant recovery and myeloma control. Lastly, isolating the effect of the GM-CSF adjuvant will address whether any effect observed is related solely to the vaccine. To compare the proportion of patients alive and in complete response at one year post-transplant between patients receiving DC/MM vaccine / GM-CSF with lenalidomide maintenance therapy to those receiving lenalidomide maintenance therapy with or without GM-CSF. Primary Objective: Immunologically: To compare the effect of DC/MM vaccine / GM-CSF with lenalidomide maintenance therapy to lenalidomide maintenance therapy alone or with GM-CSF on treatment-induced expansion of myeloma-specific T cells, defined as a 2.4-fold increase from pre-therapy to peak post-treatment levels. Clinically: To compare DC/MM vaccine / GM-CSF with lenalidomide maintenance therapy to lenalidomide maintenance therapy with or without GM-CSF with respect to: myeloma response, conversion of partial to complete response, disease progression, treatment-related mortality, progression-free survival, overall survival, toxicities according to the CTCAE v4.0, incidence of infections, and measures of minimal residual disease at one year post transplant (or approximately 10 months Secondary from randomization). Secondary exploratory analyses will also be conducted to compare in a pairwise Objectives: fashion the vaccine arm, lenalidomide / GM-CSF arm, and lenalidomide alone arm to describe the proportion of patients with collection of tumor cells who reach randomization, compliance with vaccine, and reproducibility of the vaccine manufacturing based on the release criteria. Immunologically: To compare each of the treatment arms for the percent of patients achieving at least a 10-fold expansion of myeloma-specific T cells, expansion of myeloma antigen-specific T cells by tetramer analysis, quantification of T cell subsets and PD-1 expressing lymphocytes, quantification of

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.1 Protocols Open to Accrual

Protocol Number: BMT CTN 1401 natural killer cells and identification of activation and inhibitory ligands, assessment of natural killer cell- mediated killing of myeloma targets, and assessment of humoral response against whole myeloma cells and myeloma-associated antigens by SEREX. Team Principals: Name: Email: David Avigan [email protected] Chairs: David Chung [email protected] Nina Shah [email protected] Officer: Marcelo Pasquini [email protected] Courtney Nelson [email protected] Coordinators: Kelly O’Brien [email protected] Medical Monitor: Marcie Riches [email protected] Statistician: Brent Logan [email protected] Contract Rep: Nancy Poland [email protected] Additional Members: Email: PRC Approval Date: 12/19/2014 Natalie Callander [email protected] DSMB Approval Date: 02/04/2015 Adam Cohen [email protected] Opened to Accrual: 07/25/2016 Steven Devine [email protected] Closed to Accrual: N/A Yvonne Efebera [email protected] Target Accrual: 188 patients Hillard Lazarus [email protected] Total Accrual as of 3/31/17: 33 Adam Mendizabal [email protected] Reporting Period Accrual: 33 Aaron Rapoport [email protected] IND Number: 16655 Jacalyn Rosenblatt [email protected] Recent Version Released: 03/20/2017 David Siegel [email protected] Additional Member: Email: Robert Soiffer [email protected] Edmund Waller [email protected] The study was approved by the PRC in December 2014 and DSMB in February 2015. The FDA provided Key Highlights: notice that the study may proceed in October 2015. Version 1.0 of the protocol was released to centers for IRB submission in January 2016. The study was activated on July 25, 2016, and the first patient was enrolled on August 1, 2016. Fifteen centers (5 Affiliate and 10 Core Centers) have been activated. The study is well ahead of projected Reporting Period accrual. Update: Two abstracts on translating the single center cellular therapy manufacturing process to multiple centers were accepted for presentation at the ISCT and SCT Annual Meetings in May 2017. 1. Development and management of a multi-center, center-specific cellular therapy manufacturing approach: The experience of the BMT CTN Protocol #1401. To be presented: 25th ISCT Annual Meeting, London, UK, May 2017 Presentations: 2. Translation of a single-center cellular therapy manufacturing approach to a multi-center, center- specific manufacturing platform: The experience of the BMT CTN Protocol #1401. To be presented: 38th SCT Annual Meeting, Liverpool, UK, May 2017

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.1 Protocols Open to Accrual BMT CTN 1401 Target accrual = 188 patients

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.1 Protocols Open to Accrual BMT CTN 1501

Protocol Number: BMT CTN 1501 A randomized, Phase II, multicenter, open label study evaluating sirolimus and prednisone in patients Title: with refined Minnesota standard risk, Ann Arbor 1/2 confirmed acute graft-versus-host disease Acute GVHD is a frequent complication of allogeneic HCT involving activation of donor T-lymphocytes against host tissues. Despite immune suppression prophylaxis, up to 50% of HCT recipients will experience acute GVHD of varying severity. The mainstay of treatment of acute GVHD for over 3 decades has been high-dose corticosteroids. Advances are needed in primary therapy of acute GVHD, as standard corticosteroid therapy is incompletely successful and associated with toxicity. Additionally, a growing body of evidence suggests that standard-risk GVHD patients can be identified using clinical Rationale: and biomarker-based risk stratification tools. Lower-intensity therapy may be effective and spare toxicity in this setting. Existing data support safety and activity of sirolimus as a sole, steroid-free primary therapy in acute GVHD; however, a prospective randomized trial is needed. Using a combined risk stratification approach, this study will select a standard-risk (refined Minnesota standard risk, Ann Arbor 1/2 risk) acute GVHD population and conduct a randomized Phase II trial examining acute GVHD response rates after primary therapy with either sirolimus or standard prednisone therapy. To assess the rate of complete / partial remission on day 28 post-randomization in patients with Primary Objective: standard-risk acute GVHD defined by both clinical and Ann Arbor 1/2 risk status. To evaluate among treatment arms: proportion of patients with complete / partial remission and steroid dose 0.25 mg/kg or less, proportion of response, treatment failure, incidence of chronic GVHD, incidence of systemic infections, event-free survival, overall survival, disease-free survival, GVHD-free Secondary Objectives: survival, non-relapse mortality, steroid dose, topical therapy, discontinuation of immune suppression, incidence of EBV-associated lymphoproliferative disorder, incidence of hyperglycemia, steroid and sirolimus associated complications, cytomegalovirus reactivation, and patient reported outcomes. Team Principals: Name Email PRC Approval Date: 12/9/2015 Joseph Pidala [email protected] DSMB Approval Date: 2/5/2016 Chairs: Margaret MacMillan [email protected] Opened to Accrual: 10/31/2016 Chair / Officer: Mehdi Hamadani [email protected] Closed to Accrual: N/A Coordinator: Terry Pritchard [email protected] Target Accrual: 150 patients Medical Monitor: Natasha Kekre [email protected] Total Accrual as of 03/31/17: 25 patients Statistician: Brent Logan [email protected] Reporting Period Accrual: 25 patients Contract Rep: Pam Budnick [email protected] IND Number: N/A Additional Members: Email Recent Version Released: 07/02/2015 Amin Alousi [email protected] Additional Members: Email Claudio Anasetti [email protected] Madan Jagasia [email protected] Joe Antin [email protected] Lauren Kunz [email protected] Kate Bickett [email protected] Eric Leifer [email protected] Javier Bolaños-Meade [email protected] John Levine [email protected] Peter Dawson [email protected] Adam Mendizabal [email protected] Nancy DiFronzo [email protected] William Merritt [email protected] James Ferrera [email protected] Marco Mielcarek [email protected] Vincent Ho [email protected] Roy Wu [email protected] Shernan Holtan [email protected] The study was approved by the PRC in December 2015 and DSMB in February 2016. Version 1.0 of the protocol was released to centers for IRB submission in April 2016. Thirty-three centers committed to Key Highlights: participate on the study.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.1 Protocols Open to Accrual

Protocol Number: BMT CTN 1501 The study was activated in October 2016 and is currently open to enrollment at 18 of 33 possible participating centers. Accrual is on target with 25 patients enrolled. Reporting Period The DSMB approved a protocol amendment in November 2016, including the removal of the Update: required DEXA scan assessment as well as secondary endpoints of incidence of osteoporosis and change in bone mineral density. These changes will be reflected in the next protocol amendment scheduled to be released in Spring 2017.

BMT CTN 1501 Target accrual = 150 patients

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.1 Protocols Open to Accrual BMT CTN 1503

Protocol Number: BMT CTN 1503 A study to compare bone marrow transplantation to standard care in adolescents and young adults Title: with severe sickle cell disease HCT from an HLA-matched sibling donor is curative in children with sickle cell disease. However, HCT is used sparingly for young adults with sickle cell disease, in part because HCT-related complications are more likely in adults compared to children. HCT-related complications add to the burden of morbidity and mortality and typically occur within the first 1-2 years after HCT. While the burden of morbidity is also relatively high for young adults with severe sickle cell disease, death occurs later. This trial aims to study whether the up-front risk of morbidity and mortality associated with HCT (curative treatment) will eventually result in better survival compared to the standard of care (non-curative treatment). Not everyone with severe sickle cell disease will have a tissue-matched donor needed for HCT. Therefore, Rationale: the trial will assign patients to a donor arm and a no donor arm based on whether a tissue-matched donor is available. Two years after enrollment, it is hypothesized the survival difference between the treatment arms will be no more than 15%. If the difference is greater than 15%, it is unlikely to result in longer-term survival advantage for those who receive HCT. Secondly, this trial aims to establish whether HCT will protect patients from sickle-related events and organ injury while resulting in better quality of life and mean pain intensity compared to standard of care. The findings of this trial have the potential to change the treatment option for young adults with sickle cell disease, from a supportive care approach to one that is curative. To compare overall survival at 2 years after biological assignment between the donor and no donor Primary Objective: arms. Those assigned to the donor arm are expected to undergo HCT while those on the no donor arm are expected to receive standard of care supportive therapy. To compare changes in sickle cell disease-related events (pulmonary hypertension, cerebrovascular events, renal function, avascular necrosis, and leg ulcers) and functional outcomes (6-minute walk distance, health-related quality of life, cardiac function, pulmonary function, and mean pain intensity as Secondary Objectives: assessed by a multidimensional electronic pain diary) from baseline to 2 years after assignment to treatment arm. Secondary objectives for the donor arm include neutrophil recovery, platelet recovery, graft failure, chimerism, acute and chronic GVHD, idiopathic pneumonia syndrome, veno-occlusive disease, and central nervous system toxicity. Team Principals: Name Email PRC Approval Date: 12/15/2015 Lakshmanan lakshmanan.krishnamurti@ DSMB Approval Date: 04/06/2016 Chairs: Krishnamurti choa.org Opened to Accrual: 11/28/2016 Mark Walters [email protected] Closed to Accrual: N/A Officer: Mary Eapen [email protected] Target Accrual: 200 Coordinator: Jamie Garrison [email protected] Total Accrual as of 3/31/17: 3 Medical Monitor: Angie Smith [email protected] Reporting Period Accrual: 3 Statistician: Donna Neuberg [email protected] IDE Number: N/A Contract Rep: Casie Lyon (Emory) [email protected] Last Version Released: 12/29/2016 Additional Members: Email Additional Members: Email Allistair Abraham [email protected] Elizabeth Klings [email protected] Nintya Bakshi [email protected] Lauren Kunz [email protected] Beth Blackwell [email protected] John Levine [email protected] Andrew Campbell [email protected] Robert McKinstry [email protected] Carlton Dampier [email protected] Adam Mendizabal [email protected] Laura De Castro [email protected] Courtney Nelson [email protected] Nancy DiFronzo [email protected] Julie Panepinto [email protected]

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.1 Protocols Open to Accrual

Protocol Number: BMT CTN 1503 Nahed El Kassar [email protected] Marlene Peters Lawrence [email protected] Fuad El Rassi [email protected] Shannon Smith [email protected] Nancy Geller [email protected] Wally Smith [email protected] John Gorscan [email protected] Kristin Stevenson [email protected] Anne Haight [email protected] Keith Sullivan [email protected] Kathryn Hassell [email protected] Edmund Waller [email protected] Carolyn Hoppe [email protected] Catherine Wu [email protected] Naynesh Kamani [email protected] This study is different from other BMT CTN studies as it is being funded by two separate NIH grants. One is held by Emory University, which is acting as the clinical coordinating center for the study. The other is held by the BMT CTN, which is acting as the DCC. Emory is responsible for contracting with Key Highlights: participating sites and the per patient reimbursements while the BMT CTN is responsible for other study management activities, including site activation, data collection, and monitoring. Emory and the BMT CTN DCC collaborate on these and other protocol development and trial management activities. The protocol was approved by the PRC in December 2015. Forty sites plan to participate. The protocol was approved by the DSMB in April 2016, and version 1 was released to centers in May 2016. For this study, the NMDP IRB agreed to serve as a central IRB as part of a pilot project. Participating sites chose whether to use the NMDP IRB or their own IRB. The NMDP IRB approved version 1.0 of the protocol in July 2016. The study was opened to enrollment in November 2016. Protocol version 2.0 was released to centers in December 2016 and approved by the NMDP IRB in Reporting Period January 2017. The version 2.0 amendment included updates to inclusion criteria and follow-up Update: instructions as well as additional quality of life measures and research samples. Initial accrual was behind projections, with delays primarily attributed to scheduling eligibility assessments, the increased consenting timeframe for non-malignant diseases, and ongoing activation of participating sites. The protocol team worked closely with sites to identify and address barriers to activation and accrual. All 40 participating centers are anticipated to be activated by June 2017, and accrual is anticipated to increase once the study is open at all centers.

BMT CTN 1503 Target accrual = 200 patients

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.1 Protocols Open to Accrual BMT CTN 1505

Protocol Number: BMT CTN 1505 Title: A randomized recruitment intervention trial (RECRUIT) The lack of minority participation in clinical trials is a long-standing problem. This lack of diversity in clinical trial participation is a barrier to the development of new therapies because of potential racial / ethnic differences in response to treatment. Very little rigorous research has been conducted regarding Rationale: approaches to increasing subject diversity in clinical trials. This trial tests an enhanced training program based on what was learned from a previous recruitment trial, the literature, and on an intervention mapping strategy to improve and enhance implementation of a recruitment program to increase subject diversity in clinical trials that require physician referrals.

Primary Objective: To test an intervention targeting clinical trial site investigators and coordinators to increase subject diversity in multi-site treatment trials for diseases that require physician referral. Secondary To compare intervention and control sites on the number of referrals from community physicians, mean Objectives: potential and enrolled participant satisfaction scores, and numbers and types of recruitment activities. TEAM PRINCIPALS Name Email ACCRUAL Barbara Tilley (RECRUIT) [email protected] Opened: 4/28/15 Chairs: Adam Mendizabal (BMT CTN) [email protected] Closed: N/A Officer: N/A Target: N/A Coordinator: RECRUIT Total as of 3/31/16: N/A Medical Monitor: N/A Reporting Period: N/A Statistician: RECRUIT The RECRUIT study is conducted by Dr. Barbara Tilley, a PhD statistician at the University of Texas Health Science Center at Houston. The study is funded by a National Institute on Minority Health and Health Disparities grant, and the grant allows for collaboration among other NIH-funded networks / groups. Participating centers are randomized into one of two arms: intervention or control. The intervention centers receive an educational recruitment program and will work with the RECRUIT team to enhance and individualize their recruitment methods. Training includes an all-day kickoff meeting, 4-5 one hour training webinars, and follow-up calls with RECRUIT team members. The control centers follow their institution’s standard recruitment practices. All participating centers send a monthly screening logs and recruitment activities checklist to the RECRUIT coordinating center. Centers are also required to distribute anonymous satisfaction surveys screened for and/or enrolled on the selected BMT CTN “parent” studies. The RECRUIT team will collect recruitment data until the sites have completed Key Highlights: recruitment to the parent studies or for approximately two years. Dr. Tilley presented the study to the BMT CTN Steering Committee in December 2014, and the Steering Committee approved the Network’s participation. Three BMT CTN “parent” studies were selected to be included in the RECRUIT study: 1203, 1301, and 1302. The RECRUIT team screened BMT CTN Core and Consortia Centers for eligibility, including minimum of 25% minority population within 30 mile radius of the center and minimum of six patients projected to be enrolled on the three parent studies annually. BMT CTN Core and Consortia Centers were invited to participate in the study in January 2015, and 13 of the 16 eligible centers agreed to participate. For this study, the investigators and coordinators at participating centers are the research subjects. Consents were obtained from participants and centers were randomized in February 2015. The training kickoff meetings for intervention centers were held in April 2015, and centers were activated starting that month. Two of the randomized centers were ultimately unable to participate and withdrew from the study. Eleven randomized centers are participating. Reporting Period Update: The study is slated to close in April 2017 at the end of the planned two year study period.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.2 Protocols that Completed Accrual during this Reporting Period

7.2 Protocols that Completed Accrual during this Reporting Period BMT CTN Protocols that Completed Accrual during this Reporting Period (April 1, 2016 – March 31, 2017) BMT CTN Protocol Title Protocol # 1202 Prospective multi-center cohort for the evaluation of biomarkers predicting risk of complications and mortality following allogeneic HCT 1203 A multi-center Phase II trial randomizing novel approaches for graft-versus-host disease prevention compared to contemporary controls 1205 Easy-to-read informed consent (ETRIC) for hematopoietic cell transplantation clinical trials

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.2 Protocols that Completed Accrual during this Reporting Period BMT CTN 1202

Protocol Number: BMT CTN 1202

Title: Prospective multi-center cohort for the evaluation of biomarkers predicting risk of complications and mortality following allogeneic HCT

While HCT offers the only cure for many patients with malignant and non-malignant hematologic diseases, this treatment is associated with significant risks, leading to high rates of morbidity and mortality. There is a critical need for more effective prevention and treatment strategies for HCT- associated complications. The most serious of the latter include GVHD, cancer recurrence, organ toxicity, and opportunistic infection. Although some clinical variables (e.g., recipient age, donor- recipient HLA mismatch) predict higher risk of some events (e.g., GVHD, infection), no diagnostic tests exist that reliably predict occurrence, severity, or response to therapy of any of these complications. Recent compelling results from single center studies suggest that biomarkers can be identified that stratify patients into discrete risk groups for some outcomes and for overall mortality. However, these Rationale: relatively small studies generally lack the statistical power or validation necessary to allow their results to be incorporated into practice. One key factor in the success of biomarker studies is the quality of clinical outcomes data that is linked to the specimens being analyzed. An adequate resource for these studies requires longitudinal sample collection integrated with longitudinal collection of comprehensive, standardized, high quality clinical data regarding complications, from onset to resolution, and regarding other clinical variables affecting risk of post-HCT outcomes. The 1202 resource is designed to allow genomic, proteomic and transcriptional data to be integrated with high quality clinical phenotype and outcomes data to identify risk factors for development and severity of acute GVHD, chronic GVHD, organ toxicity, relapse, mortality, infection and other clinically significant complications occurring after allogeneic HCT.

To establish a cohort of biologic samples collected prospectively from patients treated in BMT CTN Primary Objective: centers that will be a shared biospecimen resource for conducting future allogeneic HCT correlative studies. Team Principals: Name: Email: John Hansen [email protected] Chairs: John Levine [email protected] Officer: Wael Saber [email protected] Coordinator: Brianna Johnson [email protected] Medical Monitor: Wael Saber [email protected] Statistician: Mat Makowski [email protected] Contract Rep: Kiila Lee [email protected] Additional Members: Email: PRC Approval Date: 11/19/2012 Amin Alousi [email protected] DSMB Approval Date: 12/17/2012 Asad Bashey [email protected] Opened to Accrual: 06/11/2013 Dennis Confer [email protected] Closed to Accrual: 05/28/2016 Nancy DiFronzo [email protected] Target Accrual: 1,500 patients James Ferrara [email protected] Total Accrual as of 3/31/17: 1,741 patients Theresa Hahn [email protected] Reporting Period Accrual: 11 patients Vincent Ho [email protected] IND Number: N/A Mary Horowitz [email protected] Recent Version Released: 03/18/2015 Alan Howard [email protected] Additional Members: Email: Leslie Kean [email protected] Miguel-Angel Perales [email protected] Phillip McCarthy [email protected] Stefanie Sarantopoulos [email protected]

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.2 Protocols that Completed Accrual during this Reporting Period

Protocol Number: BMT CTN 1202 Adam Mendizabal [email protected] Steve Spellman [email protected] Bill Merritt [email protected] The BMT CTN 1202 Protocol Team was formed in March 2012. The protocol received PRC approval in November 2012 and DSMB approval in December 2012. The protocol opened to enrollment on June 11, 2013. Forty-five centers were activated. Version 2.0 of the protocol was released in August 2013 to modify the specimen collection. Version 3.0 of the protocol was released in March 2015 to continue enrollment of non-Caucasian adult and pediatric participants until 200 African American and 200 pediatric participants are enrolled and transplanted. Due to rapid accrual, >1,500 transplanted patients were enrolled by March 2015 (originally projected Key Highlights: for February 2018). However, an evaluation of enrolled patients showed fewer minority and pediatric patients than originally anticipated. To boost accrual of non-Caucasian adults and children, the DCC provided double accrual credit for non-Caucasian patients enrolled on the BMT CTN 1202 study beginning in February 2015. To increase the sample size of these patient populations even though the study accrual target was almost met, the Steering Committee also approved a protocol amendment in February 2015 to extend accrual until at least 200 African American and 200 pediatric participants were enrolled and transplanted. The DSMB approved the amendment. After the target accrual of 200 pediatric patients was met in September 2015, accrual was restricted to African American patients only. The target accrual of 200 African American patients was met during this reporting period, and the study closed to enrollment in May 2016. Data adjudication was started in October 2013 and is Reporting Period ongoing. A study-specific SOP was updated in October 2016 further outlining the process for Update: proposal submission and review. During the next reporting period, requests for proposals will be released to investigators, with the initial release to Endpoint Review Committee members. A descriptive manuscript about the adjudication of acute GVHD data was started in this reporting period and is expected to be submitted in the next reporting period.

BMT CTN 1202 Target accrual = 1,500 patients

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.2 Protocols that Completed Accrual during this Reporting Period BMT CTN 1203

Protocol Number: BMT CTN 1203

Title: A multi-center Phase II trial randomizing novel approaches for graft-versus-host disease prevention compared to contemporary controls Acute GVHD is an important cause of morbidity and mortality after allogeneic HCT. Clinically significant grade II-IV acute GVHD occurs in 34-40% of patients undergoing HLA-matched related donor HCT, 47-52% of HLA-matched unrelated donor HCT, and is further increased in those lacking HLA-matched donors. The goal of this multi-center Phase II clinical trial is to evaluate three novel GVHD prophylaxis approaches for their efficacy in improving the proportion of patients who do not develop severe acute Rationale: GVHD, chronic GVHD that requires systemic therapy, and disease progression or relapse by one year post-transplant. All treatment arms will be compared to a contemporary control group from the CIBMTR Research Database in which all patients received the most commonly used GVHD prophylaxis regimen, tacrolimus and methotrexate. The results of this study will identify the most promising approach(es) to be tested in a Phase III trial. Selection of the most promising therapy(ies) will be made based on the magnitudes of difference in the primary endpoint between each intervention group and the control. To compare one year GVHD / relapse or progression-free survival after HCT between each of three novel GVHD prophylaxis approaches and a contemporary control from the CIBMTR Research Primary Objective: Database. An event for this time to event outcome is defined as grade III-IV acute GVHD, chronic GVHD requiring systemic immunosuppressive treatment, disease relapse or progression, or death by any cause. To describe for each treatment arm: rates of grade II-IV and III-IV acute GVHD, visceral acute GVHD, Secondary Objectives: chronic GVHD, immunosuppression-free survival at one year, hematologic recovery (neutrophil and platelet), donor cell engraftment, disease relapse or progression, TRM, rates of Grade  3 toxicities according to CTCAE Version 4.0, incidence of infections, immune reconstitution, and overall survival. Team Principals: Name: Email: Javier Bolaños-Meade [email protected] Chairs: John Koreth [email protected] Ran Reshef [email protected] Officer: Marcelo Pasquini [email protected] Coordinator: Terry Pritchard [email protected] Shannon Smiley (primary) [email protected] Medical Monitors: Dianna Howard (alternate) [email protected] Statistician: Brent Logan [email protected] Contract Rep: Nancy Poland [email protected] Additional Members: Email: PRC Approval Date: 03/25/2013 Amin Alousi [email protected] DSMB Approval Date: 05/02/2013 Joseph Antin [email protected] Opened to Accrual: 09/17/2014 Kate Bickett [email protected] Closed to Accrual: 06/30/2016 Nancy DiFronzo [email protected] Target Accrual: 270 patients Nancy Geller [email protected] Total Accrual as of 3/31/16: 279 patients David Jacobsohn [email protected] Reporting Period Accrual: 20 patients Richard Jones [email protected] IND Number: 119524 Margaret MacMillan [email protected] Recent Version Released: 07/20/2015 Adam Mendizabal [email protected] Additional Members: Email: Marco Mielcarek [email protected] David Porter [email protected]

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.2 Protocols that Completed Accrual during this Reporting Period

Protocol Number: BMT CTN 1203 Joseph Pidala [email protected] Daniel Weisdorf [email protected] The protocol was approved by the PRC in March 2013 and DSMB in May 2013; it was released to centers in December 2013 and opened to enrollment in September 2014. Key Highlights: Protocol version 3.0 was released to sites in July 2015. Changes include tightening of pre-transplant required assessment timeframes as well as minor additions to eligibility criteria and clarifications concerning adverse event reporting. Twenty-nine of 31 activated centers enrolled patients on the trial.

Reporting Period A total of 259 patients were enrolled in the last reporting period, and an additional 20 patients Update: were enrolled in this period for a total of 279 patients. Accrual was completed and closed in June 2016, ten month ahead of projected. The ERC process is scheduled to begin in Spring 2017.

BMT CTN 1203 Target accrual = 270 patients

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.2 Protocols that Completed Accrual during this Reporting Period BMT CTN 1205

Protocol Number: BMT CTN 1205 Title: Easy-to-read informed consent (ETRIC) for hematopoietic cell transplantation clinical trials This study hypothesizes that use of a novel evidence-based ETRIC form template with enhanced readability and processability components will be associated with higher levels of patient comprehension of BMT CTN treatment protocols than use of the existing standard institution-specific consent forms. Furthermore, the ETRIC form may be associated with lower anxiety and greater satisfaction with the consent process. Also, institutional barriers exist to the implementation of the ETRIC form, and it is important to understand what these are so that they can be addressed effectively if this form is proved to be superior to standard forms. The study has two components: Rationale: 1. Randomized Study: Randomized, multicenter, prospective comparative study of ETRIC or standard consent form to improve patient comprehension of BMT CTN parent clinical trials. Patients who are being considered for one of the clinical trials will be approached, and on providing verbal consent to 1205, will be randomized to and will undergo the consent process for the parent trial using either ETRIC or standard consent form. Assessments will be conducted for patient comprehension of the clinical trial and satisfaction and anxiety related to the consent process. 2. Evaluation Study: To understand barriers to implementation of ETRIC, site visits to 10-12 transplant centers participating in the BMT CTN parent studies will be conducted with semi- structured interviews of IRB administrators, site protocol investigators, and study coordinators. Sites will include centers that are participating and are not participating in the ETRIC study. To determine whether the ETRIC form increases patient comprehension of informed consent compared to the standard consent form for the BMT CTN 1101, 1203, and 1301 studies (considered Primary Objective: the “parent” clinical trials for the 1205 protocol). This will be achieved by comparing patient comprehension scores on the Quality of Informed Consent Part A instrument between patients randomized to the two arms. To compare additional measures of comprehension and measures of patient anxiety, satisfaction, and information location between the two arms. Specifically, these will include subjective comprehension Secondary Objectives: scores on the Quality of Informed Consent (Part B) instrument, comprehension scores on the modified Deaconess Informed Consent Comprehension Test, state anxiety scores on the State Trait Anxiety Inventory, satisfaction scores, and time taken for information location. The study will also explore patient consent rates on parent clinical trials for the two arms. Team Principals: Name: Email: Navneet Majhail [email protected] Chairs: Ryan Spellecy [email protected] Officer: Mary Horowitz [email protected] Coordinator: Alyssa Ramirez [email protected] Statistician: Sergey Tarima [email protected] Contract Rep: Kiila Lee [email protected] Additional Members: Email: PRC Approval Date: N/A Ellen Denzen [email protected] DSMB Approval Date: 03/04/2013 Amy Foley [email protected] Opened to Accrual: 11/26/2013 Iris Gersten [email protected] Closed to Accrual: 08/08/2016 Mitchell Horwitz [email protected] Target Accrual: 198 patients Lensa Idossa [email protected] Total Accrual as of 3/31/17: 198 patients Steven Joffe [email protected] Reporting Period Accrual: 27 patients Naynesh Kamani [email protected] IND Number: N/A

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.2 Protocols that Completed Accrual during this Reporting Period

Protocol Number: BMT CTN 1205 Roberta King [email protected] Recent Version Released: 07/27/2016 Heather Moore [email protected]

Elizabeth Wagner [email protected] The protocol was approved by the DSMB on March 4, 2013. Version 1.0 of the protocol and the study assessments were released to 12 centers in July 2013 and seven centers in September 2013. The study was activated for enrollment in November 2013 after several centers received IRB approval. Twenty centers have been activated on the randomized study. Accrual decreased significantly when the 0901 parent study closed unexpectedly, so it was determined that the 1203 study should be added as a new parent study. Version 2.0 of the 1205 Key Highlights: protocol was released in June 2014 to remove the parent protocol 0901 and add the parent protocol 1203. Accrual continued to lag, so Version 3.0 was released in November 2014, adding BMT CTN 1301 as another parent study. Due to an estimated 25% incompletion rate of the Quality of Informed Consent assessments (the primary endpoint), the DSMB approved an amendment to increase accrual from 160 to 198 participants. The amended protocol (v4) was released in January 2016. The protocol team addressed the incompletion rate with participating centers, and compliance increased. Version 5.0 was released in July 2016 to update the protocol because of the completion of the BMT CTN 1203 (GVHD Prophylaxis) parent study and as a result of an amendment to the BMT CTN 1301 (CNI-Free GVHD) study, which affected the informed consent. Reporting Period Update: Accrual to the Randomized Study was complete in August 2016. The primary endpoint is to compare objective comprehension scores on the QuIC Part A instrument between patients randomized to the ETRIC and the standard consent arms. Site interviews for the Evaluation Study are also complete, and the analysis nearly complete. The manuscript will be drafted in Spring 2017.

Presentation: 1. ETRIC forms for multi-center HCT clinical trials (BMT CTN 1205). Presented: Institute for Healthcare Advancement’s 14th Annual Health Literacy Conference, Irvine, CA, May 2015 BMT CTN 1205 Target accrual = 198* patients

* Target accrual was expanded from original sample size of 160 to 198.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.2 Protocols that Completed Accrual during this Reporting Period

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.3 Protocols that Completed Accrual during a Previous Reporting Period

7.3 Protocols that Completed Accrual during a Previous Reporting Period BMT CTN Protocols that Completed Accrual during a Previous Reporting Period BMT CTN Protocol Title Protocol # 0101 A randomized double-blind trial of fluconazole versus voriconazole for the prevention of invasive fungal infections in allogeneic blood and marrow transplant recipients 0102 A trial of tandem autologous stem cell transplants with or without post second autologous transplant maintenance therapy versus single autologous stem cell transplant followed by matched sibling nonmyeloablative allogeneic stem cell transplant for patients with multiple myeloma 0201 A Phase III randomized multicenter trial comparing G-CSF mobilized peripheral blood stem cell with marrow transplantation from HLA compatible unrelated donors 0202 Autologous vs. non-myeloablative allogeneic hematopoietic stem cell transplantation for patients with chemosensitive follicular non-Hodgkin’s lymphoma beyond first complete response or first partial response 0301 Fludarabine-based conditioning for allogeneic marrow transplantation from HLA-compatible unrelated donors in severe aplastic anemia 0302 Initial systemic treatment of acute GVHD: A Phase II randomized trial evaluating etanercept, mycophenolate mofetil, denileukin diftitox (Ontak), and pentostatin in combination with corticosteroids 0303 A single arm, multicenter Phase II trial of transplants of HLA-matched, CD34+ enriched, T cell depleted peripheral blood stem cells isolated by the CliniMACS system in the treatment of patients with AML in first or second morphologic complete remission 0401 Phase III Rituxan / BEAM versus Bexxar / BEAM with autologous hematopoietic stem cell transplantation for persistent or relapsed chemotherapy sensitive diffuse large B cell non-Hodgkin’s lymphoma 0402 A Phase III randomized, multicenter trial comparing sirolimus / tacrolimus with tacrolimus / methotrexate as graft-versus-host disease prophylaxis after HLA-matched, related peripheral blood stem cell transplantation 0403 A Phase III, randomized double-blind, placebo controlled trial of soluble tumor necrosis factor receptor: Enbrel (etanercept) for the treatment of acute non-infectious pulmonary dysfunction (idiopathic pneumonia syndrome) following allogeneic cell transplantation 0501 Multi-center, open label, randomized trial comparing single versus double umbilical cord blood transplantation in pediatric patients with leukemia and myelodysplasia 0502 / A Phase II study of allogeneic transplant for older patients with AML in first morphologic complete CALGB 100103 remission using a non-myeloablative preparative regimen 0601 Unrelated donor reduced intensity bone marrow transplant for children with severe sickle cell disease (SCURT) 0603 / 0604 A multi-center, Phase II trial of non-myeloablative conditioning and transplantation of partially HLA- mismatched bone marrow (0603) or umbilical cord blood from unrelated donors (0604) for patients with hematologic malignancies 0701 Phase II trial of non-myeloablative allogeneic hematopoietic cell transplantation for patients with relapsed follicular non-Hodgkin’s lymphoma beyond first complete response

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.3 Protocols that Completed Accrual during a Previous Reporting Period

BMT CTN Protocol Title Protocol # 0702 A trial of single autologous transplant with or without consolidation therapy versus tandem autologous transplant with lenalidomide maintenance for patients with multiple myeloma 0703 / Tandem autologous stem cell transplantation for patients with primary progressive or recurrent SWOG 0410 Hodgkin disease (a BMT study), Phase II 0704 / A Phase III randomized, double-blind study of maintenance therapy with CC-5013 or placebo following CALGB 100104 autologous stem cell transplantation for multiple myeloma / ECOG 100104 0801 A Phase II / III randomized, multicenter trial comparing sirolimus plus prednisone, and sirolimus / calcineurin inhibitor plus prednisone for the treatment of chronic graft-versus-host disease 0802 A multi-center, randomized, double blind, Phase III trial evaluating corticosteroids with mycophenolate mofetil versus corticosteroids with placebo as initial systemic treatment of acute GVHD 0803 High dose chemotherapy with autologous stem cell rescue for aggressive B cell lymphoma and Hodgkin lymphoma in HIV-infected patients 0804 / Phase II study of reduced-intensity allogeneic stem cell transplant for high-risk chronic lymphocytic CALGB 100701 leukemia 0805 / A Phase II study of combination of hyper-CVAD and dasatinib with or without allogeneic stem cell SWOG 0805 transplant in patients with Philadelphia chromosome positive and / or BCR-ABL positive acute lymphoblastic leukemia (a BMT study) 0901 A randomized, multi-center Phase III study of allogeneic stem cell transplantation comparing regimen intensity in patients with myelodysplastic syndrome or acute myeloid leukemia 0902 A Phase III randomized, multicenter trial testing whether exercise or stress management improves functional status and symptoms of autologous and allogeneic recipients 0903 Allogeneic hematopoietic cell transplant for hematological cancers and myelodysplastic syndromes in HIV-infected individuals 1204 Reduced-intensity conditioning for children and adults with hemophagocytic syndromes or selected primary immune deficiencies

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.3 Protocols that Completed Accrual during a Previous Reporting Period BMT CTN 0101

Protocol Number: BMT CTN 0101 A randomized double-blind trial of fluconazole versus voriconazole for the prevention of invasive fungal Title: infections in allogeneic blood and marrow transplant recipients Primary Objective: To compare the fungal-free survival rates between the two study arms through day 180. To compare the frequencies of invasive fungal infection, time to invasive fungal infection, survival rate, Secondary duration of amphotericin B or caspofungin therapy for possible invasive fungal infection, time to neutrophil Objectives: and platelet engraftment, time to and severity of acute and chronic GVHD, and adverse events and routine laboratory tests; also, to explore the quantitative aspects of the galactomannan assay. TEAM PRINCIPALS Name Email Thomas Walsh [email protected] Chairs: John Wingard [email protected] Officer: Dennis Confer [email protected] Coordinator: Iris Gersten [email protected] Statistician: Adam Mendizabal [email protected] ACCRUAL DATES Opened: 12/01/2003 PRC Approval: 11/15/2002 Closed: 09/21/2006 DSMB Approval: 01/22/2003 Target: 600 patients Last Version Released: 03/29/2006 Total: 600 patients Evaluable for Primary Analysis: 09/2007 IDE Number: G020306 (closed prior to enrollment) The study experienced a delay from DSMB approval to study activation due to prolonged negotiations for drug acquisition and funding. Ultimately, an over-encapsulated blinded drug was secured, and the trial opened to accrual in December 2003. Key Highlights: The study closed to accrual in September 2006 when 600 patients, as planned, were enrolled. The Endpoint Review Committee, which included five transplant physicians from the protocol team, spent considerable time checking and reconciling data, including a review of primary data documents to confirm diagnoses. Reporting Period The voriconazole pharmacokinetic analysis was published in the Journal of Antimicrobial Chemotherapy Update: in April 2016. 1. Design issues in a prospective randomized double-blinded trial of prophylaxis with fluconazole vs. voriconazole after allogeneic HCT. Clinical Infectious Disease. 2004 Oct 15; 39 Suppl 4:S176-180. 2. Primary results: Randomized double-blind trial of fluconazole vs. voriconazole for prevention of invasive fungal infection after allogeneic HCT. Blood. 2010 Dec 9; 116(24):5111-5118. Epub 2010 Sep 8.

Publications: 3. Cost-effectiveness analysis of voriconazole compared with fluconazole for prevention of invasive fungal infection in patients receiving allogeneic HCT. American Journal of Health-System Pharmacy. 2013 Sept 1; 70(17):1518-1527. 4. Voriconazole pharmacokinetics following HCT: Results from the BMT CTN 0101 trial. Journal of Antimicrobial Chemotherapy. Journal of Antimicrobial Chemotherapy. 2016 Aug 1; 71(8):2234-2240. Epub 2016 Apr 27. 1. Results of a randomized, double-blind trial of fluconazole vs. voriconazole for the prevention of invasive fungal infections in 600 allogeneic BMT patients. Presented: 49th ASH Annual Meeting, Atlanta, GA, December 2007. Presentations: 2. Relationship between voriconazole concentrations and the probability of breakthrough fungal infection. Presented: Interscience Conference of Antimicrobial Agents and Chemotherapy Meeting, Washington DC, June 2014.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.3 Protocols that Completed Accrual during a Previous Reporting Period BMT CTN 0102

Protocol Number: BMT CTN 0102 A trial of tandem autologous stem cell transplants with or without post second autologous transplant Title: maintenance therapy versus single autologous stem cell transplant followed by matched sibling nonmyeloablative allogeneic stem cell transplant for patients with multiple myeloma Primary Objective: To compare three-year progression-free survival between the two arms. Secondary Objectives: To compare current myeloma-stable survival, three-year overall survival, and incidence of progression. TEAM PRINCIPALS Name Email Amrita Krishnan [email protected] Chairs: David Maloney [email protected] Officer: Marcelo Pasquini [email protected] Coordinator: Kristin Knust [email protected] Statistician: Brent Logan [email protected] ACCRUAL DATES Opened: 11/15/2003 PRC Approval: 11/15/2002 Closed: 03/30/2007 DSMB Approval: 08/11/2003 Target: 710 patients Last Version Released: 05/15/2006 Total: 710 patients Evaluable for Primary Analysis: 04/2010 IND Number: 67956 Accrual and analysis for this study were based on the anticipated number of standard-risk multiple myeloma patients with an available HLA-matched sibling donor. Statistical power required that 150 standard-risk patients be assigned to the autologous-allogeneic transplant arm. Enrollment would remain open until this goal was achieved, with concurrent enrollment of both standard-risk and high- risk patients, with and without HLA-matched sibling donors. When the protocol was developed, it was estimated that 500–750 total subjects would be required, as it was assumed that 20% to 30% of subjects would have available HLA-matched sibling donors. The study closed to enrollment on March 30, 2007, after 150 patients declared their intent to receive an allogeneic transplant. A total of 710 subjects were required to obtain 189 subjects with standard-risk disease biologically assigned to the autologous-allogeneic transplant arm. Patients were followed for three years after their second transplant. Key Highlights: The Endpoint Review Committee formed in July 2008 after all patients completed maintenance therapy; the Committee conducted an independent assessment of the study’s primary and secondary endpoints. This preliminary review demonstrated many inconsistencies between the reported data and interpretation of disease response by transplant centers. Adjudication of such discrepancies was required, with source document review and consultation with the institutional PIs. The Endpoint Review Committee acknowledged the inherent difficulties in interpreting disease response in multiple myeloma, which suggests ongoing review of incoming data is preferred during active accrual for future myeloma clinical trials conducted by the BMT CTN. The Endpoint Review Committee completed review of all patients in June 2010. The primary manuscript was published in Lancet Oncology in September 2011. A review of long term follow-up data for a secondary analysis was completed in February 2014. A manuscript on heavy light chain ratio normalization was published during this reporting period. An Reporting Period abstract and manuscript on long term follow-up and quality of life data are expected to be submitted Update: in the next reporting period. 1. Use of biological assignment in HCT clinical trials. Clinical Trials. 2008; 5(6):607-616. Publications: 2. Tandem vs. single autologous HCT for the treatment of multiple myeloma: a systematic review and

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.3 Protocols that Completed Accrual during a Previous Reporting Period

Protocol Number: BMT CTN 0102 meta-analysis. Journal of the National Cancer Institute. 2009 Jul 1; 101(13):964; author reply 966- 967. Epub 2009 Jun 17. [Comment on: Journal of the National Cancer Institute 101(2):100-106, 2009]. 3. Primary results: Autologous HCT followed by allogeneic or autologous HCT in patients with multiple myeloma (BMT CTN 0102): A Phase 3 biological assignment trial. Lancet Oncology. 2011 Dec; 12(13):1195-1203. Epub 2011 Sep 29. 4. Heavy / light chain ratio normalization prior to transplant is of independent prognostic significance in multiple myeloma: A BMT CTN 0102 correlative study. British Journal of Haematology. 2016 Jun 13. [Epub ahead of print]. 1. Biologic assignment clinical trials in HCT for multiple myeloma: baseline characteristics by treatment allocation from BMT CTN 0102 according to availability of an HLA-matched sibling donor. Presented: 49th ASH Annual Meeting, Atlanta, GA, December 2007. 2. Tandem autologous HCT with or without maintenance therapy vs. single autologous HCT followed by HLA matched sibling non-myeloablative allogeneic HCT for patients with standard risk multiple myeloma: results from the BMT CTN 0102 trial. Presented: 52nd ASH Annual Meeting, Orlando, FL, December 2010. 3. Tandem autologous HCT with or without maintenance therapy vs. single autologous HCT followed by HLA-matched sibling non-myeloablative allogeneic HCT for patients with high risk multiple myeloma: results from the BMT CTN 0102 trial. Presented: 52nd ASH Annual Meeting, Orlando, FL, December Presentations: 2010. 4. Tandem autologous HCT vs. single autologous HCT followed by HLA matched sibling non- myeloablative allogeneic HCT for patients with standard risk multiple myeloma: results from the BMT CTN 0102 trial. Presented: 13th International Myeloma Workshop, Paris, France, May 2011. 5. Immunoglobulin free light chain and heavy chain / light chain assays – comparison with electrophoretic responses in multiple myeloma. Presented: 53rd ASH Annual Meeting, San Diego, CA, December 2011. 6. Heavy light chain ratio normalization allows identification of electrophoretic non-complete response patients with improved outcomes: A long term follow up update for BMT CTN 0102 correlative study. Presented: 20th Congress of the European Hematology Association, Vienna, Austria, June 2015.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.3 Protocols that Completed Accrual during a Previous Reporting Period BMT CTN 0201

Protocol Number: BMT CTN 0201 A Phase III randomized multicenter trial comparing G-CSF mobilized peripheral blood stem cell with marrow Title: transplantation from HLA compatible unrelated donors To compare two-year survival probabilities between patients receiving PBSC versus marrow transplants from Primary Objective: unrelated donors using an intent-to-treat analysis. To compare survival, incidences of neutrophil and platelet engraftment, graft failure, acute GVHD, chronic Secondary GVHD, time off immunosuppressive therapy, relapse, infections, adverse events, immune reconstitution, and Objectives: quality of life. Donors in each arm of the study were compared for time to return to baseline toxicity score, complete blood count and white blood count differential values after donation, and quality of life. TEAM PRINCIPALS Name Email Chair: Claudio Anasetti [email protected] Officer: Dennis Confer [email protected] Coordinator: Kristin Knust [email protected] Statistician: Brent Logan [email protected] ACCRUAL DATES Opened: 01/20/2004 PRC Approval: 05/05/2003 Closed: 10/16/2009 DSMB Approval: 09/04/2003 Target: 550 patients Last Version Released: 09/15/2006 Total: 551 patients Evaluable for Primary Analysis: 10/2011 IND Number: 6821 A coordinated effort involving transplant and donor centers and the NMDP/Be The Match Search Coordinating Unit made this study possible. It is the only study of its kind, and the BMT CTN is the only mechanism through which it could be accomplished. A total of 551 patients and unrelated donors were Key Highlights: enrolled on this study, which successfully closed to accrual on October 16, 2009. The Endpoint Review Committee was formed in January 2010 to review outcomes data and was completed in November 2011. The primary manuscript was published in the New England Journal of Medicine in October 2012. The 5 year patient QOL manuscript was published in this reporting period. A secondary analysis on donor recovery was presented at the 2016 EBMT Annual Meeting (manuscript published at the end of the Reporting Period previous reporting period). Additionally, two secondary analyses were presented at the 2017 BMT Update: Tandem Meetings: 1) exploring the discontinuation of immune suppression after transplant in 0201 and 0402 patients; and 2) assessing physician perspectives about translating research into clinical practice. The manuscripts for these analyses are in progress. 1. Human CMV-induced memory-like NKG2C(+) NK cells are transplantable and expand in vivo in response to recipient CMV antigen. Journal of Immunology. 2012 Nov 15; 189(10):5082-5088. Epub 2012 Oct 17. 2. Primary results: PBSC vs. bone marrow from unrelated donors. New England Journal of Medicine. 2012 Oct 18; 367(16):1487-96. 3. Health-related QoL of bone marrow vs. PBSC donors: a pre-specified subgroup analysis from a Phase III RCT-BMT CTN protocol 0201. Biology of Blood and Marrow Transplantation. 2014 Jan 1; 20(1):118-127. Publications: 4. Improved survival after transplantation of more donor plasmacytoid dendritic or naïve T cells from unrelated-donor marrow grafts: results from BMT CTN 0201. Journal of Clinical Oncology. 2014 Aug 1; 32(22):2365-2372. Epub 2014 Jun 30. 5. Comparison of characteristics and outcomes of trial participants and nonparticipants: Example of BMT CTN 0201 trial. Biology of Blood and Marrow Transplantation. 2015 Oct 1; 21(10):1815-1822. Epub 2015 Jun 11.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.3 Protocols that Completed Accrual during a Previous Reporting Period

Protocol Number: BMT CTN 0201 6. Infections following transplantation of bone marrow or PBSC from unrelated donors. Biology of Blood and Marrow Transplantation. 2016 Feb 1; 22(2):359-370. Epub 2015 Sep 25. 7. Recovery of unrelated donors of PBSC vs. recovery of unrelated donors of bone marrow: A prespecified analysis from the Phase III BMT CTN Protocol 0201. Biology of Blood and Marrow Transplantation. 2016 Jun 1; 22(6):1108-1116. Epub 2016 Mar 21. 8. Comparison of patient-reported outcomes in 5-year survivors who received bone marrow vs peripheral blood unrelated donor transplantation: Long-term follow-up of a randomized clinical trial. JAMA Oncology. 2016 Dec 1; 2(12):1583-1589. Epub 2016 Aug 11. 1. Health-related quality-of-life among adult unrelated stem cell donors: a BMT CTN randomized trial of marrow versus PBSC donation. Presented: 52nd ASH Annual Meeting, Orlando, FL, December 2010. 2. Increased incidence of chronic GVHD and no survival advantage with filgrastim-mobilized PBSC compared to bone marrow transplants from unrelated donors: results of BMT CTN Protocol 0201, a Phase III, prospective, randomized trial. Presented: 53rd ASH Annual Meeting, San Diego, CA, December 2011. 3. Larger numbers of donor naïve CD8+ T-cells and plasmacytoid dendritic cell precursors in allogeneic BM grafts from unrelated donors are associated with improved survival: results from BMT CTN 0201. Presented: 53rd ASH Annual Meeting, San Diego, CA, December 2011. 4. Grade III - IV acute GVHD and treatment-related mortality are reduced among recipients of larger numbers of donor naïve CD8+ T-cells and plasmacytoid dendritic cell precursors in allogeneic BM grafts from unrelated donors: results from BMT CTN 0201. Presented: 38th EBMT Annual Meeting, Geneva, Switzerland, April 2012. 5. Increased incidence of chronic GVHD and no survival advantage with filgrastim-mobilized PBSC Presentations: compared to bone marrow transplants from unrelated donors: results of BMT CTN Protocol #0201, a Phase III, prospective, randomized trial. Presented: ASCO Annual Meeting, Chicago, IL, June 2012. 6. More infections with transplantation of bone marrow vs. PBSC from unrelated donors. Presented: BMT Tandem Meetings, San Diego, CA, February 2015. 7. 5 year results of BMT CTN 0201: Unrelated donor bone marrow is associated with better psychological well-being and less burdensome chronic GVHD symptoms than peripheral blood. Presented: 57th ASH Annual Meeting, Orlando, FL, December 2015. 8. Faster recovery of unrelated donors of PBSC vs BM: A prespecified analysis from BMT CTN 0201. Presented: 42nd EBMT Annual Meeting, Valencia, Spain, April 2016. 9. Multi-state modeling identifies determinants of successful immune suppression discontinuation: Secondary analysis of BMT CTN 0201 and 0402 trials. Presented: BMT Tandem Meetings, Orlando, FL, February 2017. 10. Understanding physicians’ perspectives about translating research into clinical practice: Example of BMT CTN 0201 results. Presented: BMT Tandem Meetings, Orlando, FL, February 2017.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.3 Protocols that Completed Accrual during a Previous Reporting Period BMT CTN 0202

Protocol Number: BMT CTN 0202 Autologous vs. non-myeloablative allogeneic hematopoietic stem cell transplantation for patients with Title: chemosensitive follicular non-Hodgkin’s lymphoma beyond first complete response or first partial response Primary Objective: To compare three-year progression-free survival between the two treatment arms. To compare three-year overall survival, time to progression, time to complete and partial response, time to off-study therapy, and incidence of infections and NCI CTCAE Version 3.0 Grade ≥ 3 toxicities. Secondary objectives for the nonmyeloablative allogeneic HCT recipients include the incidence and Secondary Objectives: severity of acute and chronic GVHD and incidence of primary and secondary graft failure. Additional objectives are the efficacy of cyclophosphamide plus rituximab in vivo purging, the prediction of disease relapse by measurement of t(14;18) by quantitative polymerase chain reaction, and quality of life as measured by the SF-36 and the FACT-BMT. TEAM PRINCIPALS Name Email Ginna Laport [email protected] Chairs: Robert Negrin [email protected] Officer: Marcie Riches [email protected] Coordinator: Kristin Knust [email protected] Statistician: Marian Ewell [email protected] ACCRUAL DATES Opened: 07/28/2004 PRC Approval: 08/01/2003 Closed: 03/02/2006 DSMB Approval: 03/01/2004 Target: 480 patients Last Version Released: 01/17/2006 Total: 30 patients Evaluable for Primary Analysis: 04/2009 When the study closed to accrual in March 2006, 22 patients were enrolled on the autologous HCT + rituximab arm and eight on the allogeneic HCT + rituximab arm. Discussions with BMT CTN and Cooperative Group investigators and analysis of the CIBMTR Research Database led the Protocol Team to conclude that poor accrual on this trial came from low referrals of eligible patients by primary care oncologists. The Network continued to follow the enrolled patients for three-year survival and adverse events as recommended by the DSMB. The last patient three-year survival follow-up finished on April Key Highlights: 13, 2009. The primary results manuscript was published in Biology of Blood and Marrow Transplantation in November 2010. Important questions regarding the role of HCT for patients with follicular lymphoma must still be addressed. The NCI-funded Cooperative Group Transplant and Lymphoma Committee Chairs collaborated with the Network to design and implement a new trial with better feasibility (BMT CTN 0701, which opened on April 27, 2009, and completed accrual on October 22, 2012). Reporting Period N/A Update: 1. Primary results: Autologous vs. reduced intensity allogeneic HCT for patients with chemosensitive Publication: follicular non-Hodgkin lymphoma beyond first complete response or first partial response. Biology of Blood and Marrow Transplantation. 2011 Jul; 17(7):1051-1057. Epub 2010 Nov 10. 1. Autologous vs. reduced-intensity allogeneic HCT for patients with follicular non-Hodgkins lymphoma Presentation: beyond first complete response or first partial response. Presented: ASCO Annual Meeting, Chicago, IL, May 2008.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.3 Protocols that Completed Accrual during a Previous Reporting Period BMT CTN 0301

Protocol Number: BMT CTN 0301 Fludarabine-based conditioning for allogeneic marrow transplantation from HLA-compatible unrelated Title: donors in severe aplastic anemia To select the optimal cyclophosphamide dose in a regimen of fludarabine, cyclophosphamide, total Primary Objective: body irradiation and antithymocyte globulin, based on day 100 assessments of graft failure (primary and secondary), regimen-related toxicity, and early death. To evaluate post-transplant survival, graft failure, treatment-related mortality, and acute and chronic Secondary Objectives: GVHD. TEAM PRINCIPALS Name Email Paolo Anderlini [email protected] Chairs: Joachim Deeg [email protected] Officer: Mary Eapen [email protected] Coordinator: Iris Gersten [email protected] Statistician: Maggie Wu [email protected] ACCRUAL DATES Opened: 01/24/2006 PRC Approval: 03/31/2005 Closed: 12/02/2013 DSMB Approval: 07/15/2005 Target: 94 patients Last Version Released: 06/06/2013 Total: 97 patients Evaluable for Primary Analysis: 06/25/2014 This study was activated in January 2006. Thirty-one centers were activated, and 23 centers enrolled patients. Patient accrual was initially slower than projected. The most significant factor affecting accrual was study design, which required review of day 100 outcomes data from a sufficient number of patients to ensure that stopping boundaries were not crossed. Another factor was the lack of severe aplastic anemia patients referred for unrelated donor transplantation (85 per year average in the US). Accrual on the trial was temporarily suspended in May 2008 for DSMB review of toxicities. An amendment was released to centers in August 2008 after the consent form was revised to address the findings of the 150 mg/kg (excess toxicity) and 0 mg/kg cyclophosphamide (excess graft failure) cohorts. In addition, the stopping rules were revised to reflect a combined day 100 endpoint of graft failure and treatment-related mortality. Accrual resumed in December 2008. An amendment was released in February 2010, allowing accrual on parallel tracks using cyclophosphamide at 100 mg/kg and 50 mg/kg levels, with the proviso that if a stopping threshold was reached on 100 mg/kg, the DCC would notify the DSMB before enrolling to the 50 mg/kg dose. As a Key Highlights: result, the protocol temporarily closed less often while patients were followed to the day 100 safety point. This amendment enhanced accrual, and the DSMB recommendation in Fall 2011 to preferentially enroll on the 50mg/kg dose level until at least 20 patients with 8/8 HLA match were accrued was met. In June 2013, the protocol was amended to extend study accrual beyond the original goal of 78-81 patients to 94 patients with completion anticipated in Spring 2014. The objective was to rebalance HLA matched (8/8) and HLA-mismatched (7/8) transplants and gain more data on engraftment in the 50 mg/kg cyclophosphamide dose level. The study completed accrual with 97 patients in December 2013. In November 2013, the DSMB approved a request for an endpoint review committee to conduct a blinded data review of participants with 24 month follow-up once the 97th enrolled participant reached their Day 100. The Endpoint Review Committee formed in May 2014 and completed their review of the primary endpoint in July 2014. The primary results were published in Lancet Haematology in September 2015.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.3 Protocols that Completed Accrual during a Previous Reporting Period

Protocol Number: BMT CTN 0301 Reporting Period Primary results with additional follow-up data were presented at a poster session at the 2016 EBMT Update: Annual Meeting. 1. Optimization of therapy for severe aplastic anemia based on clinical, biological and treatment response parameters: conclusions of an international working group on severe aplastic anemia convened by the BMT CTN, March 2010. Biology of Blood and Marrow Transplantation. 2011 Mar; 17(3)291-299. Epub 2010 Oct 27. 2. Fludarabine-based conditioning for marrow transplantation from unrelated donors in severe aplastic Publications: anemia: early results of a cyclophosphamide dose deescalation study show life-threatening adverse events at predefined cyclophosphamide dose levels. Biology of Blood and Marrow Transplantation. 2012 July; 18(7):1007-1011. Epub 2012 Apr 27. 3. Primary results: Cyclophosphamide conditioning in patients with severe aplastic anaemia given unrelated marrow transplantation: a phase 1-2 dose de-escalation study. Lancet Haematology. 2015 Sep 1; 2(9):e367-375. Epub 2015 Sep 2. 1. Fludarabine-based conditioning for allogeneic marrow transplantations from unrelated donors in severe aplastic anemia: serious and unexpected adverse events in pre-defined cyclophosphamide dose levels. Presented: 53rd ASH Annual Meeting, San Diego, CA, December 2011. 2. Fludarabine-based conditioning for allogeneic marrow transplantation from unrelated donors in severe aplastic anemia: serious and unexpected adverse events in pre-defined cyclophosphamide dose levels. Presented: 38th EBMT Annual Meeting, Geneva, Switzerland, April 2012. Presentations: 3. Optimized cyclophosphamide dosing in combination with fludarabine, TBI and ATG as conditioning for unrelated donor bone marrow transplantation in severe aplastic anemia: A Phase I / II study from the BMT CTN. Presented: 56th ASH Annual Meeting, San Francisco, CA, December 2014. 4. Cyclophosphamide conditioning in patients with severe aplastic anaemia given unrelated marrow transplantation: Final results of a Phase 1-2 dose de-escalation study (BMT CTN 0301). Presented: 42nd EBMT Annual Meeting, Valencia, Spain, April 2016.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.3 Protocols that Completed Accrual during a Previous Reporting Period BMT CTN 0302

Protocol Number: BMT CTN 0302 Initial systemic treatment of acute GVHD: A Phase II randomized trial evaluating etanercept, mycophenolate Title: mofetil, denileukin diftitox (Ontak), and pentostatin in combination with corticosteroids To estimate the proportion of day 28 complete remissions for newly-diagnosed acute GVHD for each of Primary Objective: these agents given in combination with corticosteroids. To determine the proportion of patients achieving a partial response, mixed response, and progression at day 28; proportion of patients with treatment failure (no response, progression, administration of additional therapy for GVHD, or mortality) by day 14; incidence of GVHD flares requiring increasing therapy Secondary before day 90; incidences of discontinuation of immune suppression without flare by days 90, 180, and 270 Objectives: after initiation of therapy; incidence of chronic GVHD by 9 months; overall survival at 6 and 9 months after initiation of therapy; incidences of systemic infections within 3 months of initiation of therapy; and incidence of Epstein-Barr virus-associated lymphoma. TEAM PRINCIPALS Name Email Chair: Daniel Weisdorf [email protected] Officer: Marcelo Pasquini [email protected] Coordinator: Kristin Knust [email protected] Statistician: Maggie Wu [email protected] ACCRUAL DATES Opened: 08/25/2005 PRC Approval: 01/26/2004 Closed: 03/24/2008 DSMB Approval: 05/13/2004 Target: 180 patients Last Version Released: 08/21/2007 Total: 180 patients Evaluable for Primary Analysis: 12/2008 IND Number: 11726 Despite early concerns about slow accrual, the May 2006 amendment had a positive impact on the accrual rate, and the study was completed on March 24, 2008, with 180 patients enrolled as planned. That amendment involved four changes: (1) development of a second stratum (3-arm, balanced randomization with etanercept, pentostatin, and Ontak) for patients previously exposed to mycophenolate mofetil for GVHD prophylaxis; (2) enrollment of all patients with acute GVHD in whom the clinical decision to treat with corticosteroids was made at the participating center rather than to exclude those patients with upper gastrointestinal GVHD or limited skin diseases as the sole manifestations; (3) consent, enrollment, and randomization within 48 hours (previously 24) of initiating corticosteroid therapy; and (4) allowing enrollment of patients administered low-dose steroids for less than 7 days prior to enrollment. Key Highlights: The DSMB approved formation of an Endpoint Review Committee comprised of six transplant physicians from BMT CTN 0302 centers. All patients completed follow-up per protocol except two who were lost to follow up before nine months. The Endpoint Review Committee reviewed the study data for each patient, and results are published in a primary manuscript and secondary manuscripts. The results of the study suggested that mycophenolate mofetil was the most promising candidate for evaluation in a Phase III study. BMT CTN protocol 0802 was developed as a Phase III, randomized double blind, placebo controlled trial to evaluate the addition of mycophenolate mofetil versus placebo to systemic corticosteroids as initial therapy for acute GVHD. Protocol 0802 was closed due to futility in November 2011, and study results were published in a primary manuscript. A pharmacogenetics secondary analysis was conducted, and the manuscript was accepted for publication in Clinical Transplantation. Additionally, a validation analysis of microRNA signature for the prediction, Reporting Period diagnosis, and prognosis of acute GVHD was undertaken using the lab samples and data obtained on this Update: and other studies (BMT CTN 0402 and 0802). The manuscript is drafted and will be submitted in the next reporting period.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.3 Protocols that Completed Accrual during a Previous Reporting Period

Protocol Number: BMT CTN 0302 1. Optimal two-stage randomized Phase II clinical trials. Clinical Trials. 2005 Feb 1; 2(1):5-12. 2. Primary results: Etanercept, mycophenolate, denileukin or pentostatin plus corticosteroids for acute GVHD, a randomized Phase 2 trial from the BMT CTN. Blood. 2009 Jul 16; 114(3)511-517. Epub 2009 May 14. 3. Mycophenolate pharmacokinetics and association with response to acute GVHD treatment from the BMT CTN. Biology of Blood and Marrow Transplantation. 2010 Mar 1; 16(3):421-429. 4. GVHD treatment: predictors of survival. Biology of Blood and Marrow Transplantation. 2010 Dec 1; 16(12):1693-1699. Epub 2010 Jun 10. 5. Acute GVHD biomarkers measured during therapy can predict treatment outcomes: A BMT CTN study. Blood. 2012 Apr 19; 119(16):3854-3860. Epub 2012 Mar 1. Publications: 6. Lymphocyte phenotype during therapy for acute GVHD: A brief report from BMT CTN 0302. Biology of Blood and Marrow Transplantation. 2013 Mar 1; 19(3)481-485. Epub 2012 Dec 12. 7. A prognostic score for acute GVHD based on biomarkers: A multicentre study. Lancet Haematology. 2015 Jan 1; 2(1):e21-29. Epub 2014 Dec 23. 8. A refined risk score for acute GVHD that predicts response to initial therapy, survival, and transplant- related mortality. Biology of Blood and Marrow Transplantation. 2015 Apr 1; 21(4):761-767. Epub 2015 Jan 10. 9. Circulating angiogenic factors associated with response and survival in patients with acute GVHD: Results from BMT CTN 0302 and 0802. Biology of Blood and Marrow Transplantation. 2015 Jun 1; 21(6):1029-1036. Epub 2015 Mar 7. 10. Pharmacogenetics of steroid responsive acute GVHD. Clinical Transplantation. [In Press]. 1. A Phase II randomized trial evaluating etanercept, mycophenolate mofetil, denileukin diftitox and pentostatin in combination with corticosteroids in 180 patients with newly diagnosed acute GVHD. Presented: 50th ASH Annual Meeting, San Francisco, CA, December 2008. 2. GVHD biomarkers measured during treatment independently predict response to therapy and survival: A Blood and Marrow Transplant Clinical Trials Network study. Presented: 37th EBMT Annual Meeting, Paris, France, April 2011. 3. A new Ann Arbor grading system uses biomarkers to risk stratify patients for non-relapse mortality at Presentations: the onset of acute GVHD. Presented: 40th EBMT Annual Meeting, Milan, Italy, March-April 2014. 4. Circulating angiogenic factors as biomarkers of acute GVHD onset and response to therapy: repair and regeneration vs. endothelial damage and inflammation. Presented: 56th ASH Annual Meeting, San Francisco, CA, December 2014. 5. A biomarker algorithm defines onset grades of acute GVHD with distinct non-relapse mortality. Presented: 56th ASH Annual Meeting, San Francisco, CA, December 2014. 6. Prognostic impact of follistatin in acute GVHD: Results from BMT CTN 0302 and 0802. Presented: BMT Tandem Meetings, San Diego, CA, February 2015.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.3 Protocols that Completed Accrual during a Previous Reporting Period BMT CTN 0303

Protocol Number: BMT CTN 0303 A single arm, multicenter Phase II trial of transplants of HLA-matched, CD34+ enriched, T cell depleted Title: peripheral blood stem cells isolated by the CliniMACS system in the treatment of patients with AML in first or second morphologic complete remission To assess disease-free survival six months after transplant. Outcome measures to assess this endpoint were Primary Objective: death or relapse. To assess infusional toxicity, time to neutrophil and platelet engraftment, incidence and severity of acute and Secondary chronic GVHD, incidence of TRM, incidence of Epstein-Barr virus after transplant, lymphoproliferative Objectives: disorder, time to leukemia relapse, probability of survival and disease-free survival at 2 years, and the proportion of grafts with both > 5 x 106/kg CD34+ cells and < 1 x 105/kg CD3 cells. TEAM PRINCIPALS Name Email Steve Devine [email protected] Chairs: Richard O’Reilly [email protected] Officer: Marcelo Pasquini [email protected] Coordinator: Kristin Knust [email protected] Statistician: Adam Mendizabal [email protected] ACCRUAL DATES Opened: 06/30/2005 PRC Approval: 03/17/2004 Closed: 12/24/2008 DSMB Approval: 10/15/2004 Target: 45 patients Last Version Released: 11/13/2006 Total: 47 patients Evaluable for Primary Analysis: 07/2009 IDE Number: 11965 There was a delay between PRC and DSMB approvals, due to a determination by the DSMB in April 2004 that safety data were required for donors and recipients. This required protocol resubmission to the DSMB. The long interval between DSMB approval and study activation was due to lengthy processing of the IDE. The protocol was submitted on September 30, 2004, to the FDA; it was approved by the FDA on December 28, 2004, and released to centers in January 2005. The study was opened to accrual on June 30, 2005, after centers had received training by Miltenyi Biotech, Inc. and provided laboratory standard operating procedures for review. The study completed accrual in Key Highlights: December 2008 with 47 patients enrolled. The Endpoint Review Committee completed an independent assessment of the primary and secondary endpoints of the study. The primary manuscript was published in Biology and Blood and Marrow Transplantation in February 2011. In January 2014, the FDA approved the CliniMACS CD34 Reagent System as a Humanitarian Use Device for the prevention of graft-versus-host disease in patients with AML in first complete remission undergoing allogeneic HCT from a matched related donor. The BMT CTN 0303 data were used by the FDA in their determination. Reporting Period The follow-up study to BMT CTN 0303, a Phase III calcineurin inhibitor-free GVHD prophylaxis protocol Update: utilizing the CliniMACS CD34 Reagent System (BMT CTN 1301), is ongoing. 1. Primary results: Low risk of chronic GVHD and relapse associated with T cell depleted PBSC transplantation for AML in first remission: results of the BMT CTN Protocol 0303. Biology of Blood and Marrow Transplantation. 2011 Sep 1; 17(9):1343-1351. Epub 2011 Feb 12. 2. Characteristics of CliniMACS(®) System CD34-enriched T cell-depleted grafts in a multicenter trial for AML Publications: – BMT CTN Protocol 0303. Biology of Blood and Marrow Transplantation. 2012 May 1; 18(5):690-697. Epub 2011 Aug 26. 3. Comparative outcomes of donor graft CD34+ selection and immune suppressive therapy as GVHD prophylaxis for patients with AML in complete remission undergoing HLA-matched sibling allogeneic HCT.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.3 Protocols that Completed Accrual during a Previous Reporting Period

Protocol Number: BMT CTN 0303 Journal of Clinical Oncology. 2012 Sep 10; 30(26):3194-3201. 1. HLA-identical sibling-matched, CD34+ selected, T cell depleted PBSC following myeloablative conditioning for first or second remission AML, results of BMT CTN Protocol 0303. Presented: 51st ASH Annual Meeting, New Orleans, LA, December 2009. 2. Comparative effectiveness analysis of CD34+ selected, T cell depleted HLA-matched sibling grafts on Presentations: allogeneic HCT for patients with AML in complete remission. Presented: BMT Tandem Meetings, Orlando, FL, February 2010. 3. Characteristics of CD34-enriched products processed at multiple centers using the CliniMACS System - BMT CTN 0303. Presented: 16th Annual International Society for Cellular Therapy meeting, Philadelphia, PA, May 2010.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.3 Protocols that Completed Accrual during a Previous Reporting Period BMT CTN 0401

Protocol Number: BMT CTN 0401 Phase III Rituxan / BEAM versus Bexxar / BEAM with autologous hematopoietic stem cell Title: transplantation for persistent or relapsed chemotherapy sensitive diffuse large B cell non-Hodgkin’s lymphoma To compare progression-free survival after autologous HCT for chemotherapy-sensitive DLBCL using Primary Objective: Rituxan / BEAM versus Bexxar / BEAM as a pre-transplant conditioning regimen. To compare overall survival; time to progression; proportion of complete response and partial response at day 100; time to hematopoietic recovery; hematologic function; incidence of infection; maximum Secondary Objectives: mucositis score by day 21; immune reconstitution; treatment-related mortality; and development of myelodysplasia, secondary acute myelogenous leukemia, or abnormal cytogenetics. TEAM PRINCIPALS Name Email Chair: Julie Vose [email protected] Officer: Marcie Riches [email protected] Coordinator: Kristin Knust [email protected] Statistician: Maggie Wu [email protected] ACCRUAL DATES Opened: 12/07/2005 PRC Approval: 09/24/2004 Closed: 07/17/2009 DSMB Approval: 02/04/2005 Target: 224 patients Last Version Released: 01/14/2009 Total: 224 patients Evaluable for Primary Analysis: 07/2011 IND Number: 12520 This study was activated on December 7, 2005. Although diffuse large B cell non-Hodgkin lymphoma is a common indication for autologous HCT, an increasing percentage of these procedures are performed in diverse community hospitals without academic programs, so only a few transplant centers have access to large numbers of eligible patients. To increase patient accrual, additional centers were recruited, and Key Highlights: a collaboration with SWOG was developed. The study closed on July 17, 2009, after reaching its accrual goal of 224 patients. Thirty-seven centers enrolled patients on the study. An Endpoint Review Committee was formed in April 2011, completing data review in June 2011 and presenting at ASH in December 2011. The primary manuscript was published in the Journal of Clinical Oncology in March 2013. Reporting Period N/A Update: 1. Primary results: Phase III randomized study of BEAM compared with Iodine-131 tositumomab / Publication: BEAM with autologous HCT for relapsed DLBCL: results from the BMT CTN 0401 trial. Journal of Clinical Oncology. 2013 May 1; 31(13):1662-1668. Epub 2013 Mar 11. 1. Randomized Phase III trial of 131Iodine-tositumomab (bexxar) / BEAM vs. rituximab / BEAM and Presentation: autologous HCT for relapsed DLBCL: no difference in progression-free or overall survival. Presented: 53rd ASH Annual Meeting, San Diego, CA, December 2011.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.3 Protocols that Completed Accrual during a Previous Reporting Period BMT CTN 0402

Protocol Number: BMT CTN 0402 A Phase III randomized, multicenter trial comparing sirolimus / tacrolimus with tacrolimus / Title: methotrexate as graft-versus-host disease prophylaxis after HLA-matched, related peripheral blood stem cell transplantation To compare day 114 grades II through IV acute GVHD-free survival rates between patients receiving Primary Objective: sirolimus and tacrolimus with those receiving methotrexate and tacrolimus from the time of patient randomization, using an intent-to-treat analysis. To compare time to neutrophil and platelet engraftment, incidence of grades III-IV acute GVHD, mucositis severity, time to first hospital discharge after transplantation, all infections, cytomegalovirus Secondary Objectives: reactivation, thrombotic microangiopathy incidence, veno-occlusive disease during the first 100 days after transplantation, malignant disease relapse, and one-year relapse-free and overall survival rates. TEAM PRINCIPALS Name Email Joseph Antin [email protected] Chairs: Corey Cutler [email protected] Officer: Marcelo Pasquini [email protected] Coordinator: Kristin Knust [email protected] Statistician: Brent Logan [email protected] ACCRUAL DATES Opened: 11/20/2006 PRC Approval: 09/24/2004 Closed: 10/26/2011 DSMB Approval: 02/04/2005 Target: 312 patients Last Version Released: 12/03/2010 Total: 314 patients Evaluable for Primary Analysis: 07/01/2013 Although this protocol was approved by the DSMB in a timely fashion, the Network delayed activating the study until closure of BMT CTN 0101 to reduce competition for a similar patient population. Initial accrual to this study was slower than projected. Protocol version 2.0, released in June 2007, increased the allowed cholesterol / triglyceride level at study entry, removed the requirement for donor toxicity assessments, and modified the required mucositis assessment periods. In September 2007, the veno-occlusive stopping guideline was crossed, and enrollment was suspended. The DSMB approved re-opening the study in October 2007, with exclusion of the busulfan Key Highlights: and cyclophosphamide conditioning regimen. The revised protocol was released to centers in November 2007. Some centers were unable to transition to a total body irradiation-based conditioning regimen in lieu of the busulfan regimen, so additional center participation was solicited. Version 4.0 of the protocol was released in December 2010 to allow patients whose primary disease was acute biphenotypic leukemia in first or subsequent remission. Twenty-six centers (13 Core and 13 Affiliate) participated on this trial. The study completed accrual in October 2011. The protocol team began the Endpoint Data Review in December 2011. The primary manuscript was published in Blood in June 2014. A secondary analysis of immune reconstitution data is ongoing. A biomarker ancillary analysis of manuscript was published in Blood in January 2017 and presented at both the 2016 ASH Annual Reporting Period Meeting and the 2017 BMT Tandem Meetings. A secondary analysis of the BMT CTN 0201 and 0402 Update: results exploring the discontinuation of immune suppression after transplant was presented at the 2017 BMT Tandem Meetings. The manuscript is in process. 1. Sirolimus is associated with veno-occlusive disease of the liver after myeloablative allogeneic HCT. Publications: Blood. 2008 Dec 1; 112(12)4425-4431. Epub 2008 Sep 5.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.3 Protocols that Completed Accrual during a Previous Reporting Period

Protocol Number: BMT CTN 0402 2. Primary results: Tacrolimus / sirolimus vs. tacrolimus / methotrexate as GVHD prophylaxis after matched, related donor allogeneic HCT. Blood. 2014 Aug 21; 124(8): 1372-1377. Epub 2014 Jun 30. 3. Plasma biomarkers of risk for death in a multicenter Phase 3 trial with uniform transplant characteristics post-allogeneic HCT. Blood. 2017 Jan 12; 129(2):162-170. Epub 2016 Nov 8. 1. Tacrolimus / sirolimus vs. tacrolimus / methotrexate for GVHD prophylaxis after HLA-matched, related donor HCT: Results of BMT CTN trial 0402. Presented: 54th ASH Annual Annual Meeting, Atlanta, GA, December 2012. 2. Angiogenic factors, inflammation, and outcomes in myeloablative allogeneic HCT: A biomarker analysis of GVHD prophylaxis in BMT CTN Protocol 0402. Presented: BMT Tandem Meetings, Honolulu, HI, February 2016. 3. Follistatin and endoglin: Potential biomarkers of endothelial damage and non-relapse mortality Presentations: after myeloablative allogeneic HCT in BMT CTN 0402. Presented: 58th ASH Annual Meeting, San Diego, CA, December 2016. 4. Follistatin and endoglin: Potential biomarkers of endothelial damage and non-relapse mortality after myeloablative allogeneic HCT in BMT CTN 0402. Presented: BMT Tandem Meetings, Orlando, FL, February 2017. 5. Multi-state modeling identifies determinants of successful immune suppression discontinuation: Secondary analysis of BMT CTN 0201 and 0402 trials. Presented: BMT Tandem Meetings, Orlando, FL, February 2017.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.3 Protocols that Completed Accrual during a Previous Reporting Period BMT CTN 0403

Protocol Number: BMT CTN 0403

A Phase III, randomized double-blind, placebo controlled trial of soluble tumor necrosis factor receptor: Enbrel Title: (etanercept) for the treatment of acute non-infectious pulmonary dysfunction (idiopathic pneumonia syndrome) following allogeneic cell transplantation To determine the day 28 response rate following treatment with etanercept plus corticosteroids compared with Primary Objective: placebo plus corticosteroids for patients with idiopathic pneumonia syndrome (IPS) after allogeneic HCT. (Response is defined as (1) survival at day 28; and (2) discontinuation of all supplemental oxygen support for more than 72 consecutive hours by day 28.)

Secondary To evaluate response to therapy at day 56; overall mortality in patients with IPS; time to discontinuation of Objectives: supplemental oxygen; and pro-inflammatory markers of pulmonary disease in both bronchoalveolar lavage fluid and plasma of patients with IPS. TEAM PRINCIPALS Name Email Kenneth Cooke [email protected] Chairs: Gregory Yanik [email protected] Officer: Mary Horowitz [email protected] Coordinator: Roe Wright [email protected] Statistician: Maggie Wu [email protected] ACCRUAL DATES Opened: 08/27/2007 PRC Approval: 09/26/2005 Closed: 09/14/2011 DSMB Approval: 12/01/2005 Target: 60 patients Last Version Released: 06/02/2010 Total: 37 patients Evaluable for Primary Analysis: 08/26/2012 IND Number: 11726 (Part of 0302 IND) The study was activated August 27, 2007. A protocol amendment was released in January 2008 that adjusted the eligibility criteria to include patients who developed IPS within 120 days after a donor leukocyte infusion, revised definitions of cytomegalovirus infection, and revised study drug blinding logistics. An additional protocol amendment in January 2009 extended eligibility to patients who develop IPS within 180 days post transplantation or post donor leukocyte infusion. Protocol Version 4 was released in October 2009, relaxing the bronchoscopy requirements for patients less than 30 days post transplantation who were too medically unstable to undergo the procedure. Protocol Version 5 was released to centers in June 2010, reducing the sample size from 120 patients Key Highlights: (60 per arm) to 60 patients (30 per arm). Accrual continued to lag behind projections, despite the amendments. In April 2011, the DSMB approved the Protocol Team’s accrual plan for two interval assessments of enrollment; however, these accrual targets were not met, and the Protocol Team received DSMB approval to close the study on September 14, 2011. The Endpoint Review Committee was formed and reviewed the study data from March to August 2012. After completion of data review, the study results were presented at the 2013 BMT Tandem Meetings. The primary manuscript was published in Biology of Blood and Marrow Transplantation in March 2014.The final study data was submitted to the NHLBI BioLINCC data repository in December 2014.

Reporting Period A proteomic and genomic analysis of plasma and genomic cytokine and inflammatory markers is in process, Update: and a manuscript will be submitted during the next reporting period. The lab samples for the bioassay studies were finalized by the investigators for the ancillary study. 1. Primary results: Randomized, double-blind, placebo-controlled trial of soluble tumor necrosis factor receptor: Publication: Enbrel (etanercept) for the treatment of idiopathic pneumonia syndrome following allogeneic HCT: BMT CTN protocol. Biology of Blood and Marrow Transplantation. 2014 Jun 1; 20(6):858-864. Epub 2014 Mar 7. 1. Randomized, double blind, placebo-controlled trial of a TNF inhibitor (etanercept) for the treatment of Presentation: idiopathic pneumonia syndrome after allogeneic HCT, a BMT CTN study. Presented: BMT Tandem Meetings, Salt Lake City, UT, February 2013.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.3 Protocols that Completed Accrual during a Previous Reporting Period BMT CTN 0501

Protocol Number: BMT CTN 0501

Title: Multi-center, open label, randomized trial comparing single versus double umbilical cord blood transplantation in pediatric patients with leukemia and myelodysplasia

Primary Objective: To determine the efficacy of using two cord blood units versus one; the primary endpoint is one-year survival rate. To compare disease-free survival, incidences of neutrophil and platelet engraftment, chimerism, Secondary Objectives: acute GVHD, chronic GVHD, TRM, infections, immune reconstitution, and relapse in patients randomized to the two study arms. TEAM PRINCIPALS Name Email Joanne Kurtzberg [email protected] Chairs: John Wagner [email protected] Officer: Mary Eapen [email protected] Coordinator: Roe Wright [email protected] Statistician: Maggie Wu [email protected] ACCRUAL DATES Opened: 10/16/2006 PRC Approval: 01/20/2006 Closed: 02/29/2012 DSMB Approval: 04/24/2006 Target: 220 patients Last Version Released: 03/18/2010 Total: 224 patients Evaluable for Primary Analysis: 08/13/2013 This trial received PRC approval in January 2006 and DSMB approval in April 2006. In September 2006, the protocol was amended to include patient registration procedures for COG. The study was activated October 16, 2006. Ten BMT CTN Core Centers and 38 COG Centers were activated for enrollment. Accrual on this study was completed in February 2012 with 224 patients enrolled. In April 2011, the DSMB approved the Protocol Team’s request to review blinded data on patients that have met the Key Highlights: primary endpoint; this review process began in January 2012. The Endpoint Review Committee completed an independent assessment of the primary and secondary endpoints of the study. The primary study results were presented at ASH in December 2012, and the results compared to an earlier cord blood transplantation study (COBLT) were presented at the BMT Tandem Meetings in February 2013. The primary manuscript was published in the New England Journal of Medicine in October 2014. A secondary analysis of the impact of conditioning on transplant outcomes was presented as an Reporting Period oral presentation at the 2016 ASH Annual Meeting. Additional secondary analyses of immune Update: reconstitution and comparison of trial recipients to unrelated and related donor HCT recipients during the trial period are in process. Publication: 1. One-unit vs. two-unit cord-blood transplantation for hematologic cancers. New England Journal of Medicine. 2014 Oct 30; 371(18):1685-1694. 1. No survival advantage after double UCB compared to single UCB transplant in children with hematological malignancy: Results of the BMT CTN 0501 randomized trial. Presented: 54th ASH Annual Meeting, Atlanta, GA, December 2012. Presentations: 2. Superior survival after single unit UCB transplantation in children with hematological malignancies treated on BMT CTN 0501 relative to the cord blood transplantation (COBLT). Presented: BMT Tandem Meetings, Salt Lake City, UT, February 2013. 3. UCB in children with acute leukemia: Impact of conditioning regimen on transplant outcomes. Presented: 58th ASH Annual Meeting, San Diego, CA, December 2016.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.3 Protocols that Completed Accrual during a Previous Reporting Period BMT CTN 0502 / CALGB 100103

Protocol Number: BMT CTN 0502 / CALGB 100103 A Phase II study of allogeneic transplant for older patients with AML in first morphologic complete Title: remission using a non-myeloablative preparative regimen To determine if allogeneic transplantation from an HLA-matched sibling or unrelated donor using a reduced-intensity preparative regimen results in two-year disease-free survival that is better than Primary Objective: that reported in published trials evaluating standard chemotherapy among patients with AML in first complete remission who are older than 60 years of age. To evaluate two-year actuarial risk of TRM; acute and chronic GVHD and relapse rates; rate and extent of recovery of T and B cell number and function; time course of T cell, B cell, and myeloid Secondary Objectives: progenitor chimerism following this preparative regimen; and pharmacokinetics of intravenous busulfan when used in a reduced-intensity preparative regimen in patients older than 60. TEAM PRINCIPALS Name Email Steven Devine [email protected] Chairs: Sergio Giralt [email protected] Officer: Marcelo Pasquini [email protected] Coordinator: Kate Bickett [email protected] Statistician: CALGB ACCRUAL DATES 08/29/2006 CALGB PRC Approval: CALGB Opened: 01/29/2007 BMT CTN DSMB Approval: CALGB Closed: 12/29/2011 Last Version Released: 12/01/2014 Target: 136 patients

Total: 132 (41 through BMT CTN) This protocol is a collaborative effort between CALGB and BMT CTN. CALGB patient accrual began August 29, 2006; the BMT CTN activated the study January 29, 2007. The study met its original accrual goal December 29, 2008. After DSMB review, the study was re-activated in November 2009 after NCI approved a CALGB amendment to increase the accrual goal to 136 to allow adequate numbers for separate analysis of related and unrelated donor transplantations. Key Highlights: The study closed to enrollment at both CALGB and BMT CTN centers on December 29, 2011, after enrolling 132 patients. Of the 132 patients, 41 enrolled directly through the BMT CTN and were accrued by five Core Centers and three Affiliate Centers. An additional 71 of the 132 patients were accrued by six BMT CTN Core Centers that enrolled patients directly through CALGB. An abstract for the study was presented at the December 2012 ASH meeting. The primary manuscript was published in the Journal of Clinical Oncology in November 2015. Reporting Period Update: N/A 1. Phase II study of allogeneic transplantation for older patients with AML in first complete remission using a reduced-intensity conditioning regimen: Results from CALGB 100103 (Alliance Publication: for Clinical Trials in Oncology) / BMT CTN 0502. Journal of Clinical Oncology. 2015 Dec 10; 33(35):4167-4175. Epub 2015 Nov 2. 1. A Phase II study of allogeneic transplant for older patients with AML in first morphologic Presentation: complete remission using a reduced intensity preparative regimen: results from CALGB 100103 / BMT CTN 0502. Presented: 54th ASH Annual Meeting, Atlanta, GA, December 2012.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.3 Protocols that Completed Accrual during a Previous Reporting Period BMT CTN 0601

Protocol Number: BMT CTN 0601

Unrelated donor reduced intensity bone marrow transplant for children with severe sickle cell disease Title: (SCURT)

To determine one-year event-free survival after unrelated donor bone marrow transplantation in Primary Objective: patients with sickle cell disease (death, disease recurrence, or graft rejection rates at one year will be used to measure this endpoint).

To determine the effect of HCT on clinical and laboratory manifestations of sickle cell disease, inc. stroke; the incidence of other transplant-related outcomes, inc. overall survival, neutrophil and platelet recovery, grades II-IV and III-IV acute GVHD, chronic GVHD, hepatic veno-occlusive disease, idiopathic Secondary Objectives: pneumonia syndrome, central nervous system toxicity (reversible posterior leukoencephalopathy syndrome, hemorrhage, and seizures), neurocognitive dysfunction, cytomegalovirus infection, adenovirus infection, Epstein-Barr virus after transplant, lymphoproliferative disease, invasive fungal infection, donor chimerism, immune reconstitution, and health-related quality of life. TEAM PRINCIPALS Name: Email: Naynesh Kamani [email protected] Chairs: Shalini Shenoy [email protected] Officer: Mary Eapen [email protected] Coordinator: Iris Gersten [email protected] Statistician: Brent Logan [email protected] ACCRUAL DATES Opened: 06/27/2008 PRC Approval: 08/13/2007 Closed: 04/24/2014 DSMB Approval: 11/19/2007 Target: 30 BM recipients / 8 CB Last Version Released: 06/04/2014 Total: 30 BM recipients / 8 CB Evaluable for Primary Analysis: 06/04/2015 This study, known as the “SCURT” study (sickle cell unrelated transplantation), was activated in June 2008. The trial was delayed because centers were not activated until enrollment of a first patient, to minimize activating too many centers for a study that targets only 45 patients. Two Core and 16 PBMTC Centers were activated. In June 2010, the DSMB recommended an amendment to exclude cord blood grafts, due to an observed high graft failure rate after cord blood transplantation. Cord blood as a graft source was removed from Protocol Version 6. In addition, eligibility criteria were modified to increase the age limit to 19.75 years and include increased transcranial Doppler findings as a clinically significant neurological event. The amendment excluding cord blood grafts required centers to submit a revised protocol to their IRBs before continuing enrollment. Before this revision, 8 of 15 transplants used cord blood as the graft Key Highlights: source. Not unexpectedly, accrual significantly slowed. The original accrual projections and completion were revised in April 2011 to address both the pause in enrollment required by these events and the anticipated decrease in the rate of future accrual since fewer patients would have an available graft source. In May 2011, the glomerular filtration rate requirement in the protocol was adjusted to include patients 16 years of age and older. In October 2011, the protocol was modified to ensure consistent HLA- matching criteria language. The protocol was further amended in June 2012 to reduce the targeted sample size to 30 bone marrow recipients and again in December 2012 (version 10.0) to change the liver biopsy requirements from 30 days prior to initiation of alemtuzumab to 90 days prior. In December 2013, as recommended by the DSMB, study investigators were notified of the increased incidence of RPLS / PRES, and the need to maintain strict blood pressure control, as outlined in the protocol. In addition, patients and family members were informed and instructed, via a “RPLS and PRES Letter for Participants”, to report any symptoms of RPLS / PRES that may be evident to the transplant

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.3 Protocols that Completed Accrual during a Previous Reporting Period

Protocol Number: BMT CTN 0601 physician. In April 2014, the BMT CTN DCC submitted information to the Office for Human Research Protections regarding the increased incidence of PRES in BMT CTN 0601 patients. The Office for Human Research Protections responded that the report and the corrective actions were appropriate under HHS regulations and did not request any additional information. The study closed to accrual in April 2014. In June 2014, the protocol team released a “physician advisory document” for distribution to BMT CTN 0601 patients’ health care providers. The purpose of this document is to raise awareness for maintaining and controlling (via parenteral intervention if necessary) blood pressures within 10% above the baseline age-related blood pressures for sickle cell patients pre-transplant and through day 180 post transplant. This information was also added to version 11.0 of the protocol. In November 2014, the DSMB recommended the data be released at one year for analysis, preliminary publication, and an ASH abstract submission. The Endpoint Review Committee was formed in March 2015. Data review began in April 2015 and was completed in August 2015. Results were presented as an oral abstract at the ASH Annual Meeting in December 2015 and at the 2016 BMT Tandem Meetings. Reporting Period Update: The primary manuscript was published in Blood in November 2016. 1. Unrelated donor cord blood transplantation for children with severe sickle cell disease: results of one cohort from the Phase II study from the BMT CTN. Biology of Blood and Marrow Transplantation. Publication: 2012 Aug 1; 18(8):1265-1272. Epub 2012 Feb 16. 2. A BMT CTN Phase II trial of unrelated donor marrow transplantation for children with severe sickle cell disease. Blood. 2016 Nov 24; 128(21):2561-2567. Epub 2016 Sept 13. 1. A multicenter Phase II trial of unrelated donor reduced intensity bone marrow transplantation for children with severe sickle cell disease (SCURT): results of the BMT CTN 0601 study. Presented: 57th ASH Annual Meeting, Orlando, FL, December 2015. Received a Best Abstract Award. Presentations: 2. Results of the BMT CTN 0601 study: SCURT – A multicenter Phase II trial of unrelated donor reduced intensity bone marrow transplantation for children with severe sickle cell disease. Presented: BMT Tandem Meetings, Honolulu, HI, February 2016.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.3 Protocols that Completed Accrual during a Previous Reporting Period BMT CTN 0603 / 0604

Protocol Number: BMT CTN 0603 / 0604

A multi-center, Phase II trial of non-myeloablative conditioning and transplantation of partially HLA- Title: mismatched bone marrow (0603) or umbilical cord blood from unrelated donors (0604) for patients with hematologic malignancies

Primary Objective: To determine overall survival 180 days after HLA-haploidentical bone marrow transplantation or double cord blood transplantation using a non-myeloablative preparative regimen. To assess neutrophil and platelet recovery, graft failure, acute GVHD, chronic GVHD, incidence of Secondary Objectives: infection, treatment-related mortality, time to relapse / progression, overall survival time, and progression-free survival time. TEAM PRINCIPALS Name Email Claudio Brunstein (0604) [email protected] Chairs: Ephraim Fuchs (0603) [email protected] Officer: Mary Eapen [email protected] Coordinator: Kristin Knust [email protected] Statistician: Brent Logan [email protected] ACCRUAL 0603 0604 DATES Opened: 10/17/2008 12/23/2008 PRC Approval: 12/21/2007 Closed: 05/17/2010 03/31/2010 DSMB Approval: 06/06/2008 Target: 50 patients 50 patients Last Version Released: 01/28/2009 Total: 55 patients 54 patients Evaluable for Primary Analysis: 12/2010 A single Protocol Team was formed in December 2006 to develop both BMT CTN 0603 and 0604. Presentation to the DSMB for both protocols was delayed to allow competing protocols to near completion. The protocols were released to centers for IRB approval in Summer 2008. Institutions participating in both protocols were required to submit allocation schemes or prioritization plans to avoid bias. These required approval by the Protocol Team before site activation. The 0603 protocol was activated in October 2008. Eight Core Centers and 9 Affiliate Centers enrolled a Key Highlights: total of 55 patients on the trial. The study closed to enrollment in May 2010, well ahead of projections. The 0604 protocol was activated in December 2008. Eight Core Centers and 8 Affiliate Centers enrolled a total of 54 patients on the trial. The study closed to enrollment in March 2010, well ahead of projections. The Endpoint Review Committee formed in summer 2010 and conducted data review for all the primary and secondary endpoints of the study. A secondary data review with all patients followed for two years was completed in 2014. The manuscript summarizing the two year follow-up results was published in Biology of Blood and Marrow Transplantation in May 2014. 1. Primary results: Alternative donor transplantation after reduced intensity conditioning: Results of parallel Phase II trials using HLA-mismatched related bone marrow or unrelated UCB grafts. Blood. 2011 Jul 14; 118(2):282-288. Epub 2011 Apr 28. 2. Long term follow-up (including donor selection recommendations for 1101 investigators): Publications: Mismatched related and unrelated donors for allogeneic HCT for adults with hematologic malignancies. Biology of Blood and Marrow Transplantation. 2014 Oct 1; 20(10):1485-1492. Epub 2014 May 23. 3. Comparable outcomes with marrow or peripheral blood as stem cell sources for HCT from haploidentical donors after non-ablative conditioning: A matched-pair analysis. Bone Marrow Transplantation. 2016 Dec 1; 51(12):1599-1601. Epub 2016 Aug 15. 1. Phase II trial of nonmyeloablative conditioning and partially HLA-mismatched BMT for patients with Presentations: hematologic malignancies: Results of BMT CTN Protocol 0603. Presented: BMT Tandem Meetings, Honolulu, HI, February 2011. Received a Best Abstract Award.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.3 Protocols that Completed Accrual during a Previous Reporting Period

Protocol Number: BMT CTN 0603 / 0604 2. Phase II trial of non-myeloablative conditioning double UCB transplantation from unrelated donors in patients with hematologic malignancies: Results of BMT CTN Protocol 0604. Presented: BMT Tandem Meetings, Honolulu, HI, February 2011.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.3 Protocols that Completed Accrual during a Previous Reporting Period BMT CTN 0701

Protocol Number: BMT CTN 0701

Title: Phase II trial of non-myeloablative allogeneic hematopoietic cell transplantation for patients with relapsed follicular non-Hodgkin’s lymphoma beyond first complete response

Primary Objective: To measure two-year progression-free survival after allogeneic HCT with a reduced-intensity pre- transplant conditioning regimen of fludarabine, cyclophosphamide, and rituximab. To examine two-year overall survival; time to complete and partial responses; time to off-study therapy; incidences and severity of acute and chronic GVHD; treatment-related mortality; and incidences of Secondary Objectives: primary and secondary graft failure; quality of life, as measured by the SF-36 and the FACT-BMT; and the ability to predict disease relapse by measuring t(14;18) using a quantitative polymerase chain reaction. TEAM PRINCIPALS Name Email Chair: Ginna Laport [email protected] Officer: Marcie Riches [email protected] Coordinator: Iris Gersten [email protected] Statistician: Brent Logan [email protected] ACCRUAL DATES Opened: 04/27/2009 PRC Approval: 04/01/2008 Closed: 10/22/2012 DSMB Approval: 05/20/2008 Target: 65 patients Last Version Released: 05/12/2011 Total: 65 patients Evaluable for Primary Analysis: 07/02/2014 IND Application # Exempt The study was placed on the Cancer Trials Support Unit (CTSU) roster in February 2009 and endorsed by SWOG, CALGB, and ECOG. The study was activated on April 27, 2009, after several centers received IRB approval. Twelve Core Centers and 25 Affiliate Centers were activated for enrollment, 13 of which participated through the CTSU. Several initiatives were implemented to address slower-than-anticipated enrollment, including periodic study updates to transplant center PIs and Coordinators; template referral and insurance appeal letters to centers; a campaign to encourage all non-enrolling centers to enroll; and advertisements in the CTSU, Key Highlights: ASBMT, Leukemia / Lymphoma Society, and Leukemia Research Foundation newsletters. The Protocol Version 5 amendment was approved May 12, 2011. This amendment clarified the inclusion criteria to allow patients with stable follicular lymphoma to enroll if all lymph node masses are ≤ 3 cm and are smaller or unchanged in size to the most recent salvage regimen. The study closed to accrual in October 2012 when 65 patients, as planned, were enrolled. The Endpoint Review Committee formed in September 2013, once the majority of patients had completed two year follow-up. The endpoint data review was completed in June 2014, and an oral abstract was presented at the ASH Annual Meeting in December 2014. Reporting Period The primary results manuscript was published in the Biology of Blood and Marrow Transplantation in Update: August 2016. 1. Reduced-intensity conditioning with fludarabine, cyclophosphamide and high dose rituximab for Publication: allogeneic HCT for follicular lymphoma: A Phase two multicenter trial from the BMT CTN. Biology of Blood Marrow Transplantation. 2016 Aug 1; 22(8):1440-1448. Epub 2016 Apr 23. 1. Reduced intensity conditioning with rituximab yields excellent outcomes after allogeneic HCT for Presentation: relapsed follicular lymphoma: A Phase II multicenter trial from the BMT CTN (0701). Presented: 56th ASH Annual Meeting, San Francisco, CA, December 2014.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.3 Protocols that Completed Accrual during a Previous Reporting Period BMT CTN 0702

Protocol Number: BMT CTN 0702 A trial of single autologous transplant with or without consolidation therapy versus tandem autologous Title: transplant with lenalidomide maintenance for patients with multiple myeloma Primary Objective: To compare three-year progression-free survival among the three treatment arms. To compare response rates of very good partial remission or better; rates of complete remission conversion for patients not in complete remission at initiation of maintenance; overall survival; rates of Secondary Objectives: Grade  3 toxicity according to CTCAE; incidences of infections; treatment-related mortality rates; and rates of discontinuation of therapy. The study will also describe and compare quality-of-life in the three arms. TEAM PRINCIPALS Name Email Amrita Krishnan [email protected] Chairs: George Somlo [email protected] Edward Stadtmauer [email protected] Officer: Marcelo Pasquini [email protected] Coordinator: Courtney Nelson [email protected] Statistician: Beth Blackwell [email protected] ACCRUAL DATES Opened: 06/01/2010 PRC Approval: 10/31/2008 Closed: 11/15/2013 DSMB Approval: 03/18/2009 Target: 750 patients Last Version Released: 01/26/2016 Total: 758 patients Evaluable for Primary Analysis: 02/2017 IND Number: 104912 This trial is the follow-on study to BMT CTN 0102 and BMT CTN 0704 / CALGB 100104 and is known as the STaMINA (Stem Cell Transplantation for Multiple Myeloma Incorporating Novel Agents) study. It was developed by the BMT CTN Multiple Myeloma Intergroup that included representatives from SWOG, CALGB, ECOG, and BMT CTN. The protocol was placed on the CTSU roster in March 2010. This was one of Key Highlights: the high-priority trials recommended during the 2007 State of the Science Symposium. It was identified as important to assess the role of post-transplantation treatment for myeloma in the era of novel agents. The study closed to accrual ahead of projections in November 2013 with 758 patients enrolled. A long term follow-up study (BMT CTN 07LT) was released in September 2014 to allow eligible patients on 0702 to be followed and receive lenalidomide maintenance until progression. Follow-up on all enrolled patients will be complete in November 2017. The Endpoint Review Committee is completing review of primary endpoint data, and the primary results manuscript is being Reporting Period prepared. During this reporting period, the primary endpoint results were presented at the 58th ASH Update: Annual Meeting and the 16th International Myeloma Workshop. An abstract was submitted for presentation at the 2017 ASCSO Annual Meeting. 1. Comparison of autologous HCT (autoHCT), bortezomib, lenalidomide (len) and dexamethasone consolidation with len maintenance, tandem autoHCT with len maintenance and autoHCT with len maintenance for up-front treatment of patients with multiple myeloma: Primary results from the randomized Phase III trial: BMT CTN 0702 – StaMINA trial. Presented: 58th ASH Annual Meeting, Presentations: San Diego, CA, December 2016 2. Post autologous transplant (autoHCT) therapies in high risk MM. Subgroup analysis of Phase III BMT CTN 0702 STAMINA: AutoHCT followed by lenalidomide (len) maintenance vs autoHCT and len and bortezomib and dexamethasone consolidation len maintenance vs tandem autoHCT len maintenance. Presented: 16th International Myeloma Workshop, New Delhi, India, March 2017

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.3 Protocols that Completed Accrual during a Previous Reporting Period BMT CTN 0703 / SWOG 0410

Protocol Number: BMT CTN 0703 / SWOG 0410

Tandem autologous stem cell transplantation for patients with primary progressive or recurrent Title: Hodgkin disease (a BMT study), Phase II

To assess the two-year progression-free survival for patients with primary progressive or Primary Objective: recurrent Hodgkin lymphoma treated with a tandem transplant program (two cycles of high-dose therapy with autologous stem cell rescue).

To evaluate the response rate and toxicity in patients with primary progressive or recurrent Secondary Objectives: Hodgkin lymphoma treated with this regimen. TEAM PRINCIPALS Name Email Ginna Laport (BMT CTN) [email protected] Chairs: Patrick Stiff (SWOG) [email protected] Eileen Smith (SWOG) [email protected] Officers: Marcie Riches (BMT CTN) [email protected] Coordinator: SWOG Statistician: SWOG ACCRUAL DATES 10/15/2005 SWOG PRC Approval: N/A Opened: 03/18/2008 BMT CTN DSMB Approval: N/A Closed: 02/01/2009 Last Version Released: 11/07/2007 SWOG Target: 85 patients

Total: 9 BMT CTN, 89 SWOG This protocol was a collaborative effort between SWOG and BMT CTN. Six BMT CTN Core Centers enrolled patients. SWOG closed the study upon accrual completion on February 1, 2009. An Key Highlights: analysis is being performed by SWOG, and the BMT CTN provided data as requested. The primary results were presented at the ASH Annual Meeting in December 2014. The primary results manuscript was submitted for review but not accepted. Resubmission to Reporting Period Update: another journal is underway. 1. SWOG S0410 / BMT CTN 0703: A Phase II trial of tandem autologous HCT for patients with Presentation: primary progressive or recurrent Hodgkin lymphoma. Presented: 56th ASH Annual Meeting, San Francisco, December 2014.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.3 Protocols that Completed Accrual during a Previous Reporting Period BMT CTN 0704 / CALGB 100104 / ECOG 100104

Protocol Number: BMT CTN 0704 / CALGB 100104 / ECOG 100104

Title: A Phase III randomized, double-blind study of maintenance therapy with CC-5013 (NSC #703813, IND #70116) or placebo following autologous stem cell transplantation for multiple myeloma

Primary Objective: To compare the efficacy of lenalidomide and placebo as maintenance therapy after autologous HCT in terms of time to disease progression in patients with multiple myeloma. Secondary To compare complete response rates as well as progression-free and overall survival times and to determine Objectives: the feasibility of long-term treatment with lenalidomide in these patients. TEAM PRINCIPALS Name Email Kenneth Anderson (CALGB) [email protected] Sergio Giralt (BMT CTN) [email protected] Chairs: Philip Greipp (ECOG) [email protected] Philip McCarthy (CALGB) [email protected] Officer: Marcelo Pasquini [email protected] Coordinator: CALGB Statistician: CALGB ACCRUAL DATES 12/15/2004 (CALGB) Opened: PRC Approval: CALGB 05/15/2007 (BMT CTN) Closed: 07/02/2009 DSMB Approval: CALGB Target: 533 patients total (40 BMT CTN) Last Version Released: 06/15/2008 Total: 529 patients total (172 BMT CTN) Evaluable for Primary Analysis: 12/2009 This CALGB-led, ECOG-endorsed trial opened in December 2004. It was designed to determine the importance of maintenance therapy with lenalidomide for prolonging disease response and survival in patients who have undergone HCT for treatment of multiple myeloma. Its target patient population overlapped with that of BMT CTN 0102, which opened in November 2003. The Multiple Myeloma Intergroup considered a follow-on trial to BMT CTN 0102 at that time, and the accrual difficulties of CALGB 100104 were discussed. Rather than open another competing trial, BMT CTN endorsed the CALGB trial and urged its centers to open the trial through local CALGB and ECOG mechanisms as soon as 0102 reached its enrollment target, which it did in May 2007. To allow BMT CTN centers that were not part of CALGB or ECOG to participate, the DCC worked with NCI to have the trial posted to the CTSU roster. The BMT CTN Accrual Coordinator and other DCC staff worked with the CALGB Protocol Team to develop an accrual enhancement plan that included identifying and contacting Key Highlights: centers with potentially large numbers of eligible patients using the CIBMTR’s database of transplant activity. Webinars were also conducted to increase awareness of the trial. Network centers began accruing patients to this trial in summer 2007, and all of these strategies resulted in significant improvement (at least a doubling) in accrual. In December 2009, the CALGB DSMB decided to release the trial results early, due to the significantly longer time to disease progression in patients who received lenalidomide maintenance than those receiving placebo. Timely completion of this trial answered an important question in post-transplant treatment in multiple myeloma and led well into the STaMINA trial (BMT CTN 0702), which incorporates maintenance therapy in all treatment arms. This effort is a good example of how the BMT CTN has played a leadership role in developing and completing transplant trials by fostering collaboration on a national level. The primary manuscript was published in the New England Journal of Medicine and was highlighted as a contributor to one of ASCO’s 17 Major Advances in Clinical Cancer Research in 2012.

Reporting Period A follow-up analysis was conducted, and the manuscript was submitted. Two analyses were presented at Update: the International Myeloma Workshop in March: an evaluation of the effect of the crossover group and a meta-analysis that included BMT CTN 0704 results. The meta-analysis was also presented at both the ASCO

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.3 Protocols that Completed Accrual during a Previous Reporting Period

Protocol Number: BMT CTN 0704 / CALGB 100104 / ECOG 100104 Annual Meeting and the Congress of the European Hematology Association in June 2016. 1. Primary results: Lenalidomide after HCT for multiple myeloma. New England Journal of Medicine. 2012 May 10; 366(19):1770-1781. Publications: 2. Anatomy of a successful practice-changing study: a BMT CTN – NCI Cooperative Group Collaboration. Biology of Blood and Marrow Transplantation. 2013 Jun 01; 19(6)858-859. 1. Maximizing accrual to transplant trials in multiple myeloma, lessons from the BMT CTN, ECOG and CALGB collaboration. Presented: NCI ASCO Cancer Trials Accrual Symposium, Bethesda, MD, April 2010. 2. Phase III intergroup study of lenalidomide vs. placebo maintenance therapy following single autologous HCT for multiple myeloma: CALGB 100104. Presented: ASCO Annual Meeting, Chicago, IL, June 2010. 3. Phase III intergroup study of lenalidomide vs. placebo maintenance therapy following single autologous HCT for multiple myeloma: CALGB 100104. Presented: 52nd ASH Annual Meeting, Orlando, FL, December 2010. 4. Phase III intergroup study of lenalidomide vs. placebo maintenance therapy following single autologous HCT for multiple myeloma: CALGB ECOG BMT-CTN 100104. Presented: International Myeloma Workshop, Paris, France, May 2011. 5. Analysis of overall survival in the context of cross-over from placebo to lenalidomide and the incidence of second primary malignancies in the Phase III study of lenalidomide vs. placebo maintenance therapy following autologous HCT for multiple myeloma CALGB (Alliance) ECOG BMT CTN 100104. Presented: 14th International Myeloma Workshop, Kyoto, Japan April 2013. 6. Updated analysis of CALGB / ECOG / BMT CTN 100104: Lenalidomide vs. placebo maintenance therapy Presentations: after single autologous HCT for multiple myeloma. Presented: ASCO Annual Meeting, Chicago, IL, May- June 2015. 7. Analysis of second primary malignancies in CALGB (Alliance) / ECOG / BMT CTN 100104. Presented: 15th International Myeloma Workshop, Rome, Italy, September 2015. 8. Lenalidomide maintenance after high-dose melphalan and autologous HCT in multiple myeloma: A meta-analysis of overall survival. Presented: ASCO Annual Meeting, Chicago, IL, June 2016. 9. A meta-analysis of overall survival in patients with multiple myeloma treated with lenalidomide maintenance after high-dose melphalan and autologous HCT. Presented: Congress of the European Hematology Association, Copenhagen, Denmark, June 2016. 10. Overall survival and progression-free survival adjusted for treatment crossover in the CALGB / ECOG 100104 (Alliance) study of lenalidomide vs. placebo maintenance after HCT for patients with newly diagnosed multiple myeloma. Presented: 16th International Myeloma Workshop, New Delhi, India, March 2017. 11. Lenalidomide maintenance following high-dose melphalan and autologous HCT in patients with newly diagnosed multiple myeloma: A meta-analysis of overall survival. Presented: 16th International Myeloma Workshop, New Delhi, India, March 2017.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.3 Protocols that Completed Accrual during a Previous Reporting Period BMT CTN 0801

Protocol Number: BMT CTN 0801

Title: A Phase II / III randomized, multicenter trial comparing sirolimus plus prednisone, and sirolimus / calcineurin inhibitor plus prednisone for the treatment of chronic graft-versus-host disease

Primary Phase II study: To compare a treatment regimen that contains sirolimus without a calcineurin inhibitor, to a Objective: comparator regimen of sirolimus with a calcineurin inhibitor, with the goal of determining if sirolimus plus prednisone is a sufficiently promising treatment regimen for further comparison in the Phase III trial. Phase II study: To compare percent reductions in average daily dose of prednisone by 6 and 12 months; cumulative incidences of treatment failure at 1 year; prevalence of active symptomatic chronic GVHD at 1 and 2 years; cumulative incidences of discontinuation of all systemic immunosuppressive therapy at 1 and 2 years; Secondary overall and cancer progression-free survival at 1 and 2 years; candidate serum biomarkers of chronic GVHD at Objectives: baseline, 2 months, and 6 months. Phase III study: To compare percent reduction in average daily dose of prednisone at 6, 12, and 24 months; cumulative incidences of treatment failure at 1 and 2 years; prevalence of active symptomatic chronic GVHD at 1 and 2 years; cumulative incidence of discontinuation of all systemic immunosuppressive therapy at 1 and 2 years; overall and cancer progression-free survival at 1 and 2 years; candidate serum and urine biomarkers of chronic GVHD at baseline, 2 months, and 6 months. TEAM Name Email PRINCIPALS Mukta Arora [email protected] Chairs: Paul Carpenter [email protected] Officer: Marcelo Pasquini [email protected] Coordinator: Kelly O’Brien [email protected] Statistician: Brent Logan [email protected] ACCRUAL DATES Opened: 04/15/2010 PRC Approval: 05/18/2009 Closed: 12/09/2013 DSMB Approval: 09/17/2009 Target: 110 patients (Phase II) + 200 patients (Phase III) Last Version Released: 07/09/2012 Total: 161 patients Evaluable for Primary Analysis: N/A This study was rated as “high priority” at the 2007 State of the Science Symposium. The protocol was approved by the PRC in May 2009 and DSMB in September 2009; it was activated in April 2010. The trial was designed as two parallel studies of sirolimus + prednisone, sirolimus / extracorporeal photopheresis (ECP) + prednisone, and sirolimus / calcineurin inhibitor. The Protocol Team met in June 2011 to address slow accrual (n=31), particularly on the ECP study (n=6). Accrual initiatives were undertaken, but the team closed the ECP study in September 2011 after the DSMB determined it would not compromise the scientific integrity of the trial. Key Highlights: More than 100 patients were enrolled on the Phase II portion of the study, and the principles on whether to proceed to the Phase III study of the trial were applied. Overall response rates (CR+PR) at 6 months for the experimental arm (sirolimus + prednisone) were plotted relative to the respective comparator arm (sirolimus + calcineurin inhibitor + prednisone). The results indicated accrual should not proceed to Phase III but all patients should be followed for the Phase III endpoints. After the results were reviewed by the DSMB, the study was closed to enrollment in December 2013. The Endpoint Review Committee reviewed the 6 month data of all patients and completed the adjudication of the chronic GVHD response endpoint. Reporting Period The 2-year follow-up analysis will be included in the primary results analysis, and the manuscript will be Update: submitted in the next reporting period. 1. Prednisone / sirolimus compared to PDN / SRL / calcineurin inhibitor as treatment for chronic GVHD: A Presentation: randomized Phase II study from the BMT CTN. Presented: BMT Tandem Meetings, Honolulu, HI, February 2016.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.3 Protocols that Completed Accrual during a Previous Reporting Period BMT CTN 0802

Protocol Number: BMT CTN 0802 A multi-center, randomized, double blind, Phase III trial evaluating corticosteroids with Title: mycophenolate mofetil versus corticosteroids with placebo as initial systemic treatment of acute GVHD To estimate GVHD-free survival (acute or chronic) at day 56 after randomization without additional Primary Objective: therapy. To evaluate proportions of complete, partial, mixed response, no response, and progression among surviving patients at day 14, 28, and 56; treatment failure (defined as no response, progression, administration of additional therapy for GVHD, or mortality) at day 14, 28, and 56; incidence of acute GVHD flare prior to day 90; and incidence of discontinuation of immune suppression without acute GVHD flare and without disease progression/ recurrence by days 56, 180, and 360 post therapy. Additional secondary endpoints include steroid dose at day 28 and 56 post randomization, Secondary Objectives: incidence of topical / non-absorbable therapy given by day 56, incidence of chronic GVHD by 6 and 12 months post randomization, overall and GVHD-free survival at 6 and 12 months post randomization, incidences of systemic infections within 6 months of initiation of therapy, incidence of Epstein-Barr virus-associated lymphoproliferative disorder or reactivation requiring therapy, malignancy-free survival at 6 and 12 months post randomization, non-relapse mortality at 6 and 12 months, and change in patient-reported outcomes from enrollment to day 56. TEAM PRINCIPALS Name Email Javier Bolaños-Meade [email protected] Chairs: Vincent Ho [email protected] Officer: Mary Horowitz [email protected] Coordinator: Kate Bickett [email protected] Statistician: Brent Logan [email protected] ACCRUAL DATES Opened: 02/01/2010 PRC Approval: 05/18/2009 Closed: 11/18/2011 DSMB Approval: 06/30/2009 Target: 372 patients Last Version Released: 01/31/2011 Total: 236 patients Evaluable for Primary Analysis: 06/27/2013 BMT CTN 0802 is a follow-on study to the randomized Phase II 0302 study, which completed accrual and follow-up in May 2008. The protocol was approved by the PRC in May 2009 and DSMB in June 2009. The study was activated on February 1, 2010, and closed to enrollment on November 14, Key Highlights: 2011, due to crossing a futility boundary. A total of 236 patients were enrolled from 36 centers. An endpoint review was completed in March 2012, and an abstract was presented at the February 2013 Tandem meetings. The primary manuscript was published in Blood in November 2014. 1. Phase 3 clinical trial steroids / mycophenolate mofetil vs steroids / placebo as therapy for acute GVHD: BMT CTN 0802. Blood. 2014 Nov 20; 124(22):3221-3227. Epub 2014 Aug 28. 2. A prognostic score for acute GVHD based on biomarkers: A multicentre study. Lancet Haematology. 2015 Jan 1; 2(1):21-29. Epub 2014 Dec 22. 3. A refined risk score for acute GVHD that predicts response to initial therapy, survival, and Publications: transplant-related mortality. Biology of Blood and Marrow Transplantation. 2015 Apr 1; 21(4):761-767. Epub 2015 Jan 10. 4. Circulating angiogenic factors associated with response and survival in patients with acute GVHD: Results BMT CTN 0302 and 0802. Biology of Blood and Marrow Transplantation. 2015 Jun 1; 21(6):1029-1036. Epub 2015 Mar 7.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.3 Protocols that Completed Accrual during a Previous Reporting Period

Protocol Number: BMT CTN 0802 1. A multi-center, randomized, double blind, Phase III clinical trial comparing steroids / placebo vs. steroids / mycophenolate mofetil as initial therapy for acute GVHD. BMT CTN Study 0802. Presented: BMT Tandem Meetings, Salt Lake City, UT, February 2013. 2. A new Ann Arbor grading system uses biomarkers to risk stratify patients for non relapse mortality at the onset of acute GVHD. Presented: 40th EBMT Annual Meeting, Milan, Italy, March-April 2014. Presentations: 3. Circulating angiogenic factors as biomarkers of acute GVHD onset and response to therapy: repair and regeneration vs. endothelial damage and inflammation. Presented: 56th ASH Annual Meeting, San Francisco, CA, December 2014. 4. A biomarker algorithm defines onset grades of acute GVHD with distinct non-relapse mortality. Presented: 56th ASH Annual Meeting, San Francisco, CA, December 2014. 5. Prognostic impact of follistatin in acute GVHD: Results from BMT CTN 0302 and 0802. Presented: BMT Tandem Meetings, San Diego, CA, February 2015.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.3 Protocols that Completed Accrual during a Previous Reporting Period BMT CTN 0803

Protocol Number: BMT CTN 0803 High dose chemotherapy with autologous stem cell rescue for aggressive B cell lymphoma and Hodgkin Title: lymphoma in HIV-infected patients To assess overall survival after autologous HCT for chemotherapy-sensitive aggressive B cell lymphoma Primary Objective: or Hodgkin lymphoma in patients with HIV, using BEAM for pre-transplant conditioning. To evaluate time-to-progression, progression-free survival, complete remission (CR), and CR+PR (partial remission) proportion at day 100, time to progression after CR, lymphoma disease-free survival, time to hematopoietic recovery, hematologic function at day 100, toxicities, incidence of infections, treatment- Secondary Objectives: related mortality, immunologic reconstitution, assessment of microbial gut translocation and assessment of DNA in blood (clonal Ig DNA in plasma, Epstein-Barr virus DNA in plasma and peripheral blood mononuclear cells) as tumor markers. TEAM PRINCIPALS Name Email Joseph Alvarnas [email protected] Chairs: Richard Ambinder [email protected] Officer: Willis Navarro [email protected] Coordinator: Samantha Wilkins [email protected] Statistician Brent Logan [email protected] ACCRUAL DATES Opened: 07/12/2010 PRC Approval: 11/13/2009 Closed: 05/15/2013 DSMB Approval: 01/05/2010 Target: 40 patients Last Version Released: 04/30/2010 Total: 43 patients Evaluable for Primary Analysis: 07/03/2014 The study is conducted in partnership with the AIDS Malignancy Consortium, an NCI-supported clinical trials group. Additional funding is provided by the NCI program for Non-AIDS-Defining Cancers. The BMT CTN 0803 Protocol Team was formed in November 2008. In November 2009, the protocol received PRC approval, followed by DSMB approval in January 2010. It was released to centers for IRB submission in January 2010. On April 30, 2010, Protocol Version 2 was released to centers for IRB Key Highlights: submission. The amendment removed the HIV reservoir ancillary study from the protocol. Eleven Core, 4 Affiliate, and 4 AIDS Malignancy Consortium Centers participated in the study, which opened to accrual in July 2010. The study closed to accrual on May 15, 2013, after 43 patients were enrolled. The Endpoint Review Committee completed its data review in June 2014. The primary results were presented at the ASH Annual Meeting in December 2014 and included in the ASH press release. The primary results manuscript was published in August 2016. A secondary analysis was conducted Reporting Period during the reporting period; an abstract was presented at the ASH Annual Meeting, and a manuscript Update: is in development. 1. Autologous HCT for HIV-related lymphoma: Results of the BMT CTN 0803 / AMC 071 trial. Blood. Publication: 2016 Aug 25; 128(8):1050-1058. Epub 2016 Jun 13. 1. Autologous HCT in patients with chemotherapy-sensitive, relapsed / refractory HIV-associated lymphoma: Results from the BMT CTN 0803 / AIDS Malignancy Consortium (AMC-071) trial. Presented: 56th ASH Annual Meeting, San Francisco, CA, December 2014. Presentation: 2. Evaluation of immune recovery following autologous HCT in HIV-related lymphoma: Results of the BMT CTN 0803 / AMC 071 trial. Presented: 58th ASH Annual Meeting, San Diego, CA, December 2016.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.3 Protocols that Completed Accrual during a Previous Reporting Period BMT CTN 0804 / CALGB 100701

Protocol Number: BMT CTN 0804 / CALGB 100701

Title: Phase II study of reduced-intensity allogeneic stem cell transplant for high-risk chronic lymphocytic leukemia To determine if this treatment improves the current two-year rate of progression-free survival in the Primary Objective: early-disease cohort compared to historical controls, specifically assessing whether 2-year progression-free survival ≥ 70% is achievable and whether two-year progression-free survival ≤ 50% can be excluded. To evaluate whether two-year current progression-free survival ≥ 50% is achievable and two-year progression-free survival ≤ 30% can be excluded in the advanced disease cohort; objective response rate; incidences of grades 2-4 and 3-4 acute GVHD; incidence of extensive chronic GVHD; incidences of TRM at 100 days and one year; overall survival; donor chimerism for CD3+ cells at one and two Secondary Objectives: years after transplantation; presence of donor antigen-specific T cell clones before and after withdrawal of immune suppression; relapse profiles of patients with T cell responses against chronic lymphocytic leukemia to those whose chronic lymphocytic leukemia cells are not reactive; and to prospectively examine the impact of high-risk genomic features and immune-based single nucleotide polymorphisms on response, toxicity, and two-year progression-free survival to reduced- intensity allogeneic HCT. TEAM PRINCIPALS Name Email Chair: Richard Maziarz [email protected] Officer: Mary Horowitz [email protected] Coordinator: CALGB Statistician: CALGB ACCRUAL DATES Opened: 03/16/2011 PRC Approval: CALGB 12/02/2013 (early disease cohort) DSMB Approval: CALGB Closed: 01/27/2014 (adv disease cohort) Last Version Released: 01/15/2012 Target: 86 patients Evaluable for Primary Analysis: 02/2016 Total: 69 total, 27 BMT CTN This study was rated as a “very high priority” at the 2007 State of the Science Symposium. The protocol is a collaborative effort between Alliance for Clinical Trials in Oncology and BMT CTN. Alliance patient accrual began in February 2010. BMT CTN opened the trial to enrollment in March 2011. Key Highlights: Accrual to the early disease cohort remained slower than anticipated. The Alliance Data Safety and Monitoring Board determined this cohort should be closed to new patient accrual in December 2013. The advanced disease cohort remained open, and the accrual target was met. This cohort closed to accrual in January 2014.

Reporting Period Update: The data adjudication process was started. It is anticipated the primary results manuscript will be submitted during the next reporting period.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.3 Protocols that Completed Accrual during a Previous Reporting Period BMT CTN 0805 / SWOG 0805

Protocol Number: BMT CTN 0805 / SWOG 0805

A Phase II study of combination of hyper-CVAD and dasatinib with or without allogeneic stem cell Title: transplant in patients with Philadelphia chromosome positive and/or BCR-ABL positive acute lymphoblastic leukemia (a BMT study) To test whether the relapse-free survival after allogeneic HCT among Philadelphia+ and / or BCR-ABL gene+ ALL patients given an intensive short-term chemotherapy regimen of hyper-CVAD (cyclophosphamide, vincristine, Adriamycin, and dexamethasone) in combination with the tyrosine Primary Objective: kinase inhibitor dasatinib is sufficiently high to warrant further investigation, and to test whether the continuous complete remission rate for previously untreated Philadelphia+ and / or BCR-ABL+ ALL patients given an intensive short-term chemotherapy regimen of hyper-CVAD in combination with the tyrosine kinase inhibitor dasatinib is sufficiently high to warrant Phase III investigation. To investigate, in a preliminary manner, the relative effectiveness of minimum residual disease detection using real-time quantitative polymerase chain reaction for BCR/ABL versus flow cytometry to predict the Secondary Objectives: outcome of patients treated by the hyper-CVAD + dasatinib regimen and/or allogeneic stem cell transplant; estimate the frequency and severity of toxicities of the intensive short-term chemotherapy regimen in these patients; and estimate the overall survival of all patients on the study. TEAM PRINCIPALS Name Email David Porter (BMT CTN) [email protected] Chairs: Farhad Ravandi (SWOG) [email protected] Officer: SWOG Coordinator: Sandi Jo McMillan (SWOG) [email protected] Statistician: SWOG ACCRUAL DATES SWOG: 09/01/2009 PRC Approval: SWOG Opened: CTSU: 08/09/2010 DSMB Approval: SWOG Closed: 10/01/2013 Last Version Released: 04/26/2014 Target: 85 patients Evaluable for Primary Analysis: 04/2015 Total: 91 patients IND Application Number: Held by SWOG This study was rated as a “very high priority” trial during the 2007 State of the Science Symposium; the collaborative study is led by SWOG with active involvement of BMT CTN and ECOG representatives on the Protocol Team. This protocol opened to accrual to SWOG centers in September 2009 and through the CTSU in August 2010, where the study could be accessed by all BMT CTN centers. Several centers Key Highlights: affiliated with both SWOG and the BMT CTN participated in the study. The BMT CTN continues to contribute to patient reimbursement for all patients on the transplant arm. One BMT CTN Core center was activated to participate on the study through the BMT CTN and enrolled one patient. Thirteen other BMT CTN Core / Consortia centers were activated through SWOG or the CTSU and enrolled 46 total patients. Accrual was completed in October 2013. Reporting Period The primary results were published in December 2016. Update: 1. US intergroup study of chemotherapy plus dasatinib and allogeneic stem cell transplant in Publication: Philadelphia chromosome positive ALL. Blood Advances. 2016 Dec 27; 1(3):250-259. Epub 2016 Dec 27. 1. Multi-center US intergroup study of intensive chemotherapy plus dasatinib followed by allogeneic Presentation: HCT in patients with Philadelphia chromosome positive acute lymphoblastic leukemia younger than 60. Presented: 57th ASH Annual Meeting, Orlando, FL, December 2015.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.3 Protocols that Completed Accrual during a Previous Reporting Period BMT CTN 0901

Protocol Number: BMT CTN 0901 A randomized, multi-center Phase III study of allogeneic stem cell transplantation comparing regimen Title: intensity in patients with myelodysplastic syndrome or acute myeloid leukemia To compare 18-month overall survival between the two groups. The hypothesis to be tested is that Primary Objective: reducing the intensity of the conditioning regimen will decrease treatment-related mortality without increasing relapse so that overall survival will be improved. To compare disease-free survival rate after transplantation, rate of TRM, hematologic recovery, kinetics of donor cell engraftment, incidence of graft failure, incidence and severity of acute and chronic GVHD, Secondary Objectives: immune reconstitution, quality of life, rates of infectious complications, rates of ≥ grade 3 toxicities according to CTCAE, and quality of life. TEAM PRINCIPALS Name Email Mitchell Horwitz [email protected] Chairs: Bart Scott [email protected] Officer: Marcelo Pasquini [email protected] Coordinator: Brianne Allison [email protected] Statistician: Brent Logan [email protected] ACCRUAL DATES Opened: 06/02/2011 PRC Approval: 07/23/2010 Closed: 04/18/2014 DSMB Approval: 09/15/2010 Target: 356 Last Version Released: 03/03/2014 Total: 272 Evaluable for Primary Analysis: 10/2015 The concept for this protocol was approved by the Steering Committee in October 2008 after being rated as a “high priority” at the 2007 State of the Science Symposium. The Protocol Team was formed in December 2008 and held its first meeting in March 2009. The protocol was approved by the PRC in June 2010 and DSMB in September 2010. It was activated in June 2011 after several centers received IRB approval and identified potential patients. Twenty-one Core and 16 Affiliate Centers were activated, 32 of which enrolled patients. Key Highlights: Accrual to this trial was halted permanently in April 2014 after preliminary data appeared to show benefit for one approach to the intensity of conditioning for allogeneic HCT in patients eligible for the study. All patients enrolled on the protocol continued to be followed as specified in the study. All patients completed the primary endpoint of overall survival at 18 months in October 2015. The abstract was accepted as a Late Breaking Abstract and presented at the ASH Annual Meeting in December 2015. The abstract was also selected as a Special Invite Abstract and presented at the 2016 BMT Tandem Meetings. Reporting Period The primary results manuscript was published in the Journal of Clinical Oncology in February 2017. Update: 1. Myeloablative vs reduced intensity HCT for AML and MDS. Journal of Clinical Oncology. 2017 Apr Publications: 10; 35(11):1154-1161. Epub 2017 Feb 13. 1. Results of a Phase III randomized, multi-center study of allogeneic HCT after high vs. reduced intensity conditioning in patients with MDS or AML: BMT CTN 0901. Presented: 57th ASH Annual Meeting, Orlando, FL, December 2015. Late Breaking Abstract. Presentations: 2. Results of a Phase III randomized, multi-center study of allogeneic HCT after high vs. reduced intensity conditioning in patients with MDS or AML: BMT CTN 0901. Presented: BMT Tandem Meetings, Honolulu, HI, February 2016.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.3 Protocols that Completed Accrual during a Previous Reporting Period BMT CTN 0902

Protocol Number: BMT CTN 0902

Title: A Phase III randomized, multicenter trial testing whether exercise or stress management improves functional status and symptoms of autologous and allogeneic recipients

Primary Objective: To determine whether exercise or stress management improves self-reported physical and mental functioning compared to standard care at 100 days post-transplant, using an intent-to-treat analysis To evaluate whether exercise or stress management improves physical and mental functioning compared to standard care at 100 days; physical and mental functioning among the four groups; Secondary Objectives: symptoms (fatigue, pain, sleep, nausea, cancer and treatment distress) at 100 days; the number of hospital days within the first 100 days; durability of effects by comparing functional status and symptoms at 6 months; and overall survival at 6 months. TEAM PRINCIPALS Name Email Paul Jacobsen [email protected] Chairs: Stephanie Lee [email protected] Officer: Mary Horowitz [email protected] Coordinator: Laura Devillier [email protected] Statistician: Brent Logan [email protected] ACCRUAL DATES Opened: 01/03/2011 PRC Approval: 12/23/2009 Closed: 06/01/2012 DSMB Approval: 03/18/2010 Target: 700 patients Last Version Released: 03/30/2011 Total: 711 patients Evaluable for Primary Analysis: 03/25/2013 This study is the Network’s first trial examining quality of life as its primary endpoint, and it was identified as one of 11 high-priority trials during the 2007 State of the Science Symposium. The protocol was approved by the PRC in December 2009 and DSMB in March 2010. Patient materials, including exercise and stress management videos and brochures, were finalized in September 2010 and released to centers for IRB approval. The trial opened for enrollment in January 2011 when the first center received IRB approval. Protocol Version 2 was released to centers in March 2011; the Key Highlights: amendment specified three new exclusion criteria. Accrual was completed in June 2012, 17 months earlier than projected. Twenty-one centers enrolled a total of 711 patients on the trial. An Endpoint Review Committee completed their review, and an oral abstract was presented at the ASH Annual Meeting in December 2013. The primary manuscript was published in October 2014. An abstract on patient-reported quality of life was presented at the ASH Annual Meeting in December 2014. Two additional analyses and presentations were completed in 2015. Reporting Period Four secondary analysis manuscripts were published and one abstract was presented during the Update: reporting period. 1. Exercise and stress management training prior to HCT: BMT CTN 0902. Biology of Blood and Marrow Transplantation. 2014 Oct 1; 20(10):1530-1536. Epub 2014 Jun 6. 2. Patient-reported physical functioning predicts the success of HCT (BMT CTN 0902). Cancer. 2016 Jan 1; 122(1):91-98. Epub 2015 Oct 6. Publications: 3. Trajectories of quality of life after HCT: Secondary analysis of BMT CTN 0902 data. Biology of Blood and Marrow Transplantation. 2016 Nov 1; 22(11):2077-2083. Epub 2016 Aug 15. 4. Patient-reported outcomes and socioeconomic status as predictors of clinical outcomes after HCT: A study from the BMT CTN 0902 trial. Biology of Blood and Marrow Transplantation. 2016 Dec 1; 22(12):2256-2263. Epub 2016 Aug 23.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.3 Protocols that Completed Accrual during a Previous Reporting Period

Protocol Number: BMT CTN 0902 5. Pretransplantation exercise and HCT survival: A secondary analysis of BMT CTN 0902. Biology of Blood and Marrow Transplantation. 2017 Jan 1; 23(1):161-164. Epub 2016 Oct 11. 6. Cancer and treatment distress psychometric evaluation over time: A BMT CTN 0902 secondary analysis. Cancer. 2017 Apr 15; 123(8):1416-1423. Epub 2016 Nov 28. 1. Exercise and stress management training for patients undergoing autologous or allogeneic HCT. Results from BMT CTN 0902. Presented: 55th ASH Annual Meeting, New Orleans, LA, December 2013. 2. Patient-reported quality of life is an independent predictor of survival after allogeneic HCT: A secondary analysis from the BMT CTN 0902. Presented: 56th ASH Annual Meeting, San Francisco, CA, December 2014. Presentations: 3. Pre-transplant health-related quality of life factors as predictors of outcomes following HCT – a study from the BMT CTN 0902 trial. Presented: IPOS / APOS World Congress of Psycho-Oncology IPOS/APOS Meeting, Washington, DC, July 2015. 4. Cancer and treatment distress measurements in a multicenter cohort of HCT recipients. Presented: IPOS / APOS World Congress of Psycho-Oncology IPOS/APOS Meeting, Washington, DC, July 2015. 5. Psychosocial and socioeconomic status as predictors of outcomes following HCT: An ancillary study from the BMT CTN 0902 randomized controlled trial. Presented: PsychoNeuroImmunology Research Society’s 23rd Annual Scientific Meeting, Brighton, United Kingdom, June 2016.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.3 Protocols that Completed Accrual during a Previous Reporting Period BMT CTN 0903

Protocol Number: BMT CTN 0903

Title: Allogeneic hematopoietic cell transplant for hematological cancers and myelodysplastic syndromes in HIV-infected individuals Primary Objective: To assess non-relapse morality at 100 days after allogeneic HCT. To analyze disease status at day 100 post-HCT; time to hematopoietic recovery; chimerism at 30, 100, and 180 days; hematologic function at 100 and 180 days; infections; 6-month overall survival; acute Secondary Objectives: and chronic GVHD; immunologic reconstitution at 8 weeks as well as 180 and 365 days; and the impact of HCT on the HIV reservoir at day 100, 6 months, 1 year, and 2 years post-HCT for all patients and for those who have been maintained on optimized antiretroviral therapy throughout. TEAM PRINCIPALS Name Email Joseph Alvarnas [email protected] Chairs: Richard Ambinder [email protected] Officer: Willis Navarro [email protected] Coordinator: Samantha Wilkins [email protected] Statistician: Maggie Wu [email protected] ACCRUAL DATES Opened: 05/11/2012 PRC Approval: 09/15/2010 Closed: 12/03/2015 DSMB Approval: 03/29/2011 Target: 15 patients Last Version Released: 03/12/2014 Total: 18 patients Evaluable for Primary Analysis: 01/17/2017 The protocol was approved by the PRC in September 2010 and DSMB in March 2011. Protocol Version 1 was released to centers in April 2011; however, due to the need for immediate protocol amendments, study activation was delayed. Protocol Version 2 was released in January 2012, and the protocol opened to accrual in May 2012. Protocol Version 3 was released March 2014 to modify Key Highlights: guidance for antiretroviral therapy and add risks of Enfuvirtide. The study closed to screening new patients in December 2015, but it remained open for patients who already started the screening process. Like its sister study, BMT CTN 0803, this trial is a partnership with the NCI-supported AIDS Malignancy Consortium. Additional funding is provided by the NCI Cancer Therapy Evaluation Program for Non-AIDS-Defining Cancers. The last two patients were enrolled in Spring 2016, finishing accrual with 20 patients. Endpoint Reporting Period review began in September 2016, and primary analysis was completed in January 2017. An abstract Update: will be presented at the ASCO Annual Meeting in June 2017, and the primary manuscript is in development.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.3 Protocols that Completed Accrual during a Previous Reporting Period BMT CTN 1204

Protocol Number: BMT CTN 1204 Reduced-intensity conditioning for children and adults with hemophagocytic syndromes or selected Title: primary immune deficiencies To prospectively determine the 1-year overall survival in subjects treated for hemophagocytic Primary Objective: syndromes or primary immune deficiencies using a standardized, reduced-intensity conditioning protocol consisting of fludarabine, melphalan, and intermediate timing of alemtuzumab. To measure sustained engraftment; incidence of HLH reactivation and death from disease; immune reconstitution and functional immune recovery at 1-year; cumulative incidence of grade II-IV and III-IV acute and chronic GVHD; transplant-related complications (veno-occlusive disease, central nervous Secondary Objectives: system toxicity); infectious complications, including reactivation of cytomegalovirus, adenovirus, Epstein-Barr virus, invasive fungal infection, or bacterial sepsis; and overall survival and rate of sustained engraftment of specific disease subsets. TEAM PRINCIPALS Name Email Carl Allen [email protected] Chairs: Michael Pulsipher [email protected] Officer: Mary Eapen [email protected] Coordinator: Alyssa Ramirez [email protected] Statistician: Christopher Bryant [email protected] ACCRUAL DATES Opened: 11/1/2013 PRC Approval: 07/12/2013 Closed: 12/04/2015 DSMB Approval: 08/05/2013 Target: 35 HLH patients Last Version Released: 06/16/2015 Total: 47 patients Evaluable for Primary Analysis: 02/14/2017 The protocol was approved by the PRC in July 2013 and DSMB in August 2013. It was released to centers for IRB submission in September 2013. The study was activated for enrollment in November 2013, after one center had received IRB approval and was ready to enroll a patient. The time from release to activation, and first patient enrollment, was 71 days – the shortest activation timeframe for any Network protocol. Twenty-seven centers were activated, including 17 PBMTC centers. During the DSMB’s routine review of safety and efficacy data in April 2015, the Board expressed concern regarding the incidence of reversible posterior leukoencephalopathy syndrome (RPLS) or posterior reversible encephalopathy syndrome (PRES) in study patients, as three cases of PRES had been reported. The three patients had hypertension at the time of the related incidents. All physicians and BMT staff members treating 1204 patients were notified that blood pressure should be strictly controlled to prevent central nervous system toxicity, and a memo was prepared for transplant Key Highlights: centers to distribute to their enrolled 1204 patients. In June 2015, the protocol version 4 amendment was released, adding language to the protocol and consent form regarding the risk of RPLS / PRES as well as the directive to report all occurrences of RPLS / PRES via the expedited adverse event reporting system. A new appendix was also added with tables of blood pressure levels by age and weight percentiles to assist in monitoring and controlling blood pressure to prevent RPLS / PRES. This amendment also expanded the sample size from 35 patients with HLH and other hemophagocytic syndromes to 35 HLH patients with allowance for as many patients with other hemophagocytic syndromes to also be enrolled before 35 HLH patients were enrolled. The protocol was closed to enrollment in December 2015, one year ahead of projections despite the increase in sample size. A total of 36 HLH patients and 11 patients with other hemophagocytic disorders were enrolled. The primary endpoint is one year overall survival.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.3 Protocols that Completed Accrual during a Previous Reporting Period

Protocol Number: BMT CTN 1204

Reporting Period The DSMB gave their approval in Spring 2016 for the endpoint review process to begin in Fall 2016. Update: The Endpoint Review Committee completed their review in November 2016. The final report analysis will be provided to the team in Spring 2017.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.3 Protocols that Completed Accrual during a Previous Reporting Period

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.4 Protocols Released to Centers

7.4 Protocols Released to Centers BMT CTN Protocols Released to Centers (as of March 31, 2017) BMT CTN Protocol Title Protocol # 1502 Optimizing cord blood and haploidentical aplastic anemia transplantation (CHAMP) 1506 A multi-center, randomized, double-blind, placebo-controlled Phase III trial of the FLT3 inhibitor gilteritinib administered as maintenance therapy following allogeneic transplant for patients with FLT3/ITD AML

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.4 Protocols Released to Centers BMT CTN 1502

Protocol Number: BMT CTN 1502

Title: Optimizing cord blood and haploidentical aplastic anemia transplantation (CHAMP) Acquired severe aplastic anemia is a rare bone marrow failure disorder with an estimated annual incidence of 2 cases per million and with over 600 new cases in the United States each year. Most cases are thought to be related to autoimmune destruction of marrow microenvironment or hematopoietic stem cells; accordingly, the disease can be treated and often cured by either immune suppression or marrow replacement through transplantation. HCT from a HLA-matched sibling donor has become the standard of care for younger, newly diagnosed patients with long-term survival rates close to 90% in patients under 20 and around 76% for patients older than 20. However, if the patient has siblings, each of them only has a 25% chance of being a match based on HLA inheritance patterns. Horse ATG and cyclosporine immunosuppressive therapy is generally front-line treatment for severe aplastic anemia patients who lack matched sibling donors or are not good candidates for HCT. The hematopoietic response rate is 60-70%. However, up to 40% of patients eventually relapse. and an additional 10-40% develop a secondary clonal disease. For those whose disease is primary refractory or who relapse within 4-6 months after immunosuppressive therapy, most groups recommend unrelated donor HCT if an appropriately matched unrelated donor is available. Up to half of patients who initially respond to immunosuppressive therapy subsequently recur and either require long-term immune suppression or are refractory to subsequent courses of immunosuppressive therapy. Unrelated donor Rationale: HCT can be considered as a reasonable alternative for severe aplastic anemia patients in these clinical scenarios. Unfortunately, fully matched unrelated donors (HLA-A, B, C, DRB1) from worldwide registries can be identified for about 80% of Caucasians and for much lower percentages of persons of other races and / or ethnicities. Outcomes using unrelated adult donors mismatched at a single HLA-locus (7/8 HLA- matched) have proven inferior to outcomes with fully matched unrelated donors, though allowing a single HLA-locus mismatched transplant greatly expands donor availability. The goal of this protocol is to test whether optimized approaches using two alternative donor sources will achieve acceptable outcomes in severe aplastic anemia patients. Ideally, a direct comparison of the two approaches would allow us to determine a best approach. However, given 1) the rarity of the disease, 2) the fact that different centers often prefer different stem cell sources, and 3) the fact that most comparisons of alternative donor stem cell sources have shown very similar outcomes, this protocol allows both approaches to be performed, but there is no planned comparison of outcomes in the two cohorts. The hypothesis is that both approaches will result in improved survival through reduction of transplant complications including graft failure and GVHD.

Primary Objective: To assess overall survival separately in two cohorts (unrelated cord blood and haploidentical marrow) at one year post-HCT in patients with severe aplastic anemia. To assess separately in the two cohorts the proportion of patients alive and engrafted; neutrophil and Secondary platelet recovery; graft failure (primary and secondary); grades II-IV acute GVHD and chronic GVHD; Objectives: immune reconstitution; incidence of cytomegalovirus viremia / disease and Epstein-Barr virus viremia / post-transplant lymphoproliferative disease.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.4 Protocols Released to Centers

Protocol Number: BMT CTN 1502 Team Principals: Name: Email: Amy DeZern [email protected] Chairs: Andrew Dietz [email protected] Michael Pulsipher [email protected] Officer: Mary Eapen [email protected] Coordinator: Alyssa Ramirez [email protected] Medical Monitor: Weiyun Ai [email protected] Statistician: Raphael Fraser [email protected] Contract Rep: Kiila Lee [email protected] Additional Members: Email: PRC Approval Date: 12/3/2015 Paolo Anderlini [email protected] DSMB Approval Date: 10/25/2016 Joseph Antin [email protected] Opened to Accrual: N/A Robert Brodsky [email protected] Closed to Accrual: N/A Christopher Bryant [email protected] Target Accrual: 60 patients Lauri Burroughs [email protected] Total Accrual as of 3/31/17: N/A H. Joachim Deeg [email protected] Reporting Period Accrual: N/A Nancy DiFronzo [email protected] IND Number: N/A Iris Gersten [email protected] Recent Version Released: 12/8/2016 Alfred Gillio [email protected] Additional Members: Email: Mitchell Horwitz l [email protected] Brent Logan [email protected] Chatchada Karanes [email protected] Julie Talano [email protected] Lauren Kunz [email protected] Jakub Tolar [email protected] Eric Leifer [email protected] The study was approved by the PRC in December 2015 and DSMB in October 2016. Version 1.0 of the Key Highlights: protocol was released to centers in December 2016. Nineteen Core Centers have committed to participate on the study. Reporting Period The study was released to sites in December 2016 and is pending activation. It is anticipated the first Update: patient will be enrolled in May 2017.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.4 Protocols Released to Centers BMT CTN 1506

Protocol Number: BMT CTN 1506

A multi-center, randomized, double-blind, placebo-controlled Phase III trial of the FLT3 inhibitor Title: gilteritinib administered as maintenance therapy following allogeneic transplant for patients with FLT3/ITD AML This multi-center Phase III clinical trial will evaluate the impact of maintenance therapy with the FLT3 inhibitor gilteritinib on the relapse-free survival of participants with FLT3/ITD AML who have successfully undergone allogeneic HCT. A maintenance period of 2 years has been chosen based on CIBMTR data, which indicate the vast majority of relapses occur by this time after allogeneic HCT. Rationale: Because it is placebo-controlled and double-blinded, the results that emerge from this study will establish whether or not FLT3 inhibition in this setting can prevent relapse, and whether or not it has an impact on GVHD in these participants. Additionally, the trial may establish the utility of monitoring minimum residual disease using a NGS platform. A validated minimum residual disease assay would represent an important advance for the field, as it would allow for the design of more efficient trials testing novel agents in the treatment of FLT3/ITD AML. To compare relapse-free survival between participants with FLT3/ITD AML in first complete Primary Objective: remission who undergo HCT and are randomized to receive gilteritinib or placebo beginning after the time of engraftment for a two year period. To determine the safety and tolerability of gilteritinib after HCT; to compare overall survival, non- relapse mortality, event-free survival (where events include relapse, death, stopping therapy, and administration of donor lymphocyte infusion or new therapy for suspicion of disease), 6-month Secondary Objectives: cumulative incidence of grades II-IV and III-IV acute GVHD, and 12-month and 24-month cumulative incidence of mild, moderate, and severe GVHD in participants treated with gilteritinib as maintenance therapy after HCT compared to those treated with placebo; also, to examine the effect of pre- and post-transplant minimum residual disease on relapse-free and overall survival. Team Principals: Name: Email: Yi-Bin Chen [email protected] Chairs: Mark Levis [email protected] Officer: Mehdi Hamadani [email protected] Coordinator: Heather Wittsack [email protected] Medical Monitor: Erkut Bahceci [email protected] Brent Logan [email protected] Statisticians: Mat Makowski [email protected] Matt Rosales [email protected] Contract Rep: Nancy Poland [email protected] Additional Members: Email: PRC Approval Date: 02/18/2016 Steven Devine [email protected] DSMB Approval Date: 09/21/2016 Mary Horowitz [email protected] Opened to Accrual: N/A Angela James [email protected] Closed to Accrual: N/A Richard Jones [email protected] Target Accrual: 346 patients Denise King [email protected] Total Accrual as of 3/31/17: N/A Tara Lin [email protected] Reporting Period Accrual: N/A Mark Litzow [email protected] IND Number: 117548 Adam Mendizabal [email protected] Recent Version Released: 03/17/2017 Shin Mineishi [email protected] Additional Members: Email: Maxim Norkin [email protected] Robert Soiffer [email protected] Betul Oran [email protected] Kristen Sorokti-Grimm [email protected]

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 7.4 Protocols Released to Centers

Protocol Number: BMT CTN 1506 Esperanza Papadopoulos [email protected] Masumi Ueda [email protected] Marcelo Pasquini [email protected] Celalettin Ustun [email protected] Alexander Perl [email protected] Geoffrey Uy [email protected] Whitney Sheffer [email protected] Edmund Waller [email protected] The study was approved by the PRC in February 2016 and the DSMB in September 2016. Version 1.0 of the protocol was released to BMT CTN centers for site qualification and selection activities in Key Highlights: March 2017. Twenty-two Core Centers committed to participate on the study, and several Affiliate Centers are also anticipated to participate. Additionally, several international centers outside of North America plan to participate with study management via Astellas Pharma. Reporting Period The protocol was released to BMT CTN sites in March 2017 and is pending activation. It is Update: anticipated the first North American patient will be enrolled in May 2017.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 Attachment A1: Steering Committee Roster Attachment A: Committee Rosters Attachment A1: Steering Committee Roster The Executive Committee is a subcommittee of the Steering Committee. Individuals who also serve on the Executive Committee are identified by an asterisk (*).

Core Center Principal Investigators Center Amin Alousi, MD MD Anderson Cancer Center, Houston, TX Claudio Anasetti, MD H. Lee Moffitt Cancer Center, Tampa, FL Joseph Antin, MD Dana-Farber Cancer Institute, Boston, MA Frederick Appelbaum, MD Fred Hutchinson Cancer Research Center, Seattle, WA Asad Bashey, MD Northside Hospital, Atlanta, GA *Steven Devine, MD (Chair) Ohio State University, Columbus, OH Sergio Giralt, MD Memorial Sloan-Kettering Cancer Center, New York, NY *Helen Heslop, MD, DSc (Hon) (Vice-Chair) Baylor College of Medicine, Houston, TX *Richard Jones, MD (Chair-Elect) Johns Hopkins University, Baltimore, MD Joanne Kurtzberg, MD Duke University, Durham, NC Robert Lowsky, MD Stanford University, Stanford, CA Hillard Lazarus, MD Case Western Reserve University, Cleveland, OH Gregory Yanik, MD University of Michigan, Ann Arbor, MI Ryo Nakamura, MD City of Hope National Medical Center, Duarte, CA Michael Pulsipher, MD PBMTC / Children’s Hospital of Los Angeles, Los Angeles, CA Edward Stadtmauer, MD University of Pennsylvania, Philadelphia, PA Julie Vose, MD University of Nebraska, Omaha, NE Daniel Weisdorf, MD University of Minnesota, Fairfield, MN Peter Westervelt, MD, PhD Washington University, St. Louis, MO John Wingard, MD University of Florida, Gainesville, FL National Clinical Trials Network Group Center Representatives Alliance: Steven Devine, MD Ohio State University, Columbus, OH SWOG: Patrick Stiff, MD Loyola University, Chicago, IL COG: John Levine, MD, MS Mount Sinai Medical Center, New York, NY ECOG: Mark Litzow, MD Mayo Clinic, Rochester, MN Affiliate Center Representatives Center Larry Anderson, MD, PhD UT Southwestern, Dallas, TX Parameswaran Hari, MD, MS Medical College of Wisconsin, Milwaukee, WI Voravit Ratanatharathorn, MD Karmanos Cancer Institute, Detroit, MI Juan Varela, MD, PhD Medical University of South Carolina, Charleston, SC

167

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 Attachment A1: Steering Committee Roster

DCC Principal Investigators Organization *Dennis Confer, MD (Co-PI) NMDP/Be The Match, Minneapolis, MN *Mary Horowitz, MD, MS (PI) CIBMTR, Milwaukee, WI *Adam Mendizabal, PhD (Co-PI) The Emmes Corporation, Rockville, MD NHLBI and NCI Project Officers Organization *Vikram Devgan, PhD, MBA National Cancer Institute, NIH, Bethesda, MD *Nancy DiFronzo, PhD National Heart, Lung, and Blood Institute, NIH, Bethesda, MD *Nahed El Kassar, MD, PhD National Heart, Lung, and Blood Institute, NIH, Bethesda, MD *William Merritt, PhD National Cancer Institute, NIH, Bethesda, MD

168

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 Attachment A2: Biomarkers Committee Roster Attachment A2: Biomarkers Committee Roster Term Name Organization Expiration Sophie Paczesny Indiana University 2019 ([email protected]) Bloomington, IN Miguel Perales Memorial Sloan Kettering Cancer Center 2019 ([email protected]) New York City, NY Ami Bhatt Stanford University 2018 ([email protected]) Palo Alto, CA Shernan Holtan University of Minnesota 2018 ([email protected]) Minneapolis, MN Ryo Nakamura City of Hope 2018 ([email protected]) Duarte, CA Effie Petersdorf Fred Hutchinson Cancer Research C enter 2018 ([email protected]) Seattle, WA Leslie Kean (Chair) Seattle Children’s 2017 ([email protected]) Seattle, WA Dennis Confer (ex-officio) NMDP/Be The Match - ([email protected]) Minneapolis, MN Nancy DiFronzo (ex-officio) National Heart, Lung, and Blood Institute, NIH - ([email protected]) Bethesda, MD John Hansen (ex-officio) Fred Hutchinson Cancer Research Center - ([email protected]) Seattle, WA Alan Howard (ex-officio) CIBMTR - ([email protected]) Minneapolis, MN John Levine (ex-officio) Mount Sinai Medical Center - ([email protected]) New York, NY Adam Mendizabal (ex-officio) The Emmes Corporation - ([email protected]) Rockville, MD William Merritt (ex-officio) National Cancer Institute, NIH - ([email protected]) Bethesda, MD Marcelo Pasquini (ex-officio) CIBMTR - ([email protected]) Milwaukee, WI

169

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 Attachment A3: Clinical Research Associates Committee Roster

Attachment A3: Clinical Research Associates Committee Roster Term Name Organization Expiration Courtney Greene Stanford University 2019 ([email protected]) Palo Alto, CA Connie Varner University of Michigan 2019 ([email protected]) Ann Arbor, MI Adam Fiebelkorn Children’s Hospital of Wisconsin 2018 ([email protected]) Milwaukee, WI Michelle Leveque Children’s Hospital of Wisconsin 2018 ([email protected]) Milwaukee, WI Robert Thompson Medical College of Wisconsin 2018 ([email protected]) Milwaukee, WI Noah Tucker Johns Hopkins University 2018 ([email protected]) Baltimore, MD Terry Furlong Fred Hutchinson Cancer Research Center 2017 [email protected]) Seattle, WA Mildred Pasek Dana-Farber Cancer Institute 2017 ([email protected]) Boston, MA Anjela Tsirunyan City of Hope 2017 ([email protected]) Duarte, CA Kristy Applegate (Co-Chair) (ex-officio) The Emmes Corporation - ([email protected]) Rockville, MD Cynthia Couture (ex-officio) The Emmes Corporation - ([email protected]) Rockville, MD Nancy DiFronzo (ex-officio) National Heart, Lung, and Blood Institute, NIH - ([email protected]) Bethesda, MD Mary Magliocco (Co-Chair) (ex-officio) The Emmes Corporation - ([email protected]) Rockville, MD Adam Mendizabal (ex-officio) The Emmes Corporation - ([email protected]) Rockville, MD

170

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 Attachment A4: Pharmacy Committee Roster Attachment A4: Pharmacy Committee Roster Term Name Organization Expiration Aaron Cumpston West Virginia University 2019 ([email protected]) Morgantown, WV Valkal Bhatt Memorial Sloan Kettering Cancer Center 2018 ([email protected]) New York City, NY Janel Boyle University of California, San Francisco 2018 ([email protected]) San Francisco, CA Joseph Bubalo (Chair) Oregon Health Sciences University 2017 ([email protected]) Portland, OR Philip Lubanski Kansas University Medical Center 2017 ([email protected]) Kansas City, KS Melissa Sanacore Northside Hospital 2017 ([email protected]) Atlanta, GA Dennis Confer (ex-officio) NMDP/Be The Match - ([email protected]) Minneapolis, MN Iris Gersten (ex-officio) The Emmes Corporation - ([email protected]) Rockville, MD

171

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 Attachment A5: Special Populations Committee Roster

Attachment A5: Special Populations (Pediatrics / Human Subjects) Committee Roster Term Name Organization Expiration Sung Choi University of Michigan 2019 ([email protected]) Ann Arbor, MI Luis Isola Mount Sinai Medical Center 2019 ([email protected]) New York, NY Weston Miller University of Minnesota 2019 ([email protected]) Minneapolis, MN Tsiporah Shore Weill Cornell Medical College 2019 ([email protected]) New York, NY Staci Arnold Emory University 2018 ([email protected]) Atlanta, GA Javier Bolanos-Meade (Chair) Johns Hopkins 2018 ([email protected]) Baltimore, MD Jim Connelly University of Michigan 2018 ([email protected]) Ann Arbor, MI Rabi Hanna Cleveland Clinic 2018 ([email protected]) Cleveland, OH Adetola Kassim Vanderbilt University Medical Center 2018 ([email protected]) Nashville, TN Andrew Artz University of Chicago 2017 ([email protected]) Chicago, IL Shalini Shenoy St. Louis Children’s 2017 ([email protected]) St. Louis, MO Nancy DiFronzo (ex-officio) National Heart, Lung, and Blood Institute, NIH - ([email protected]) Bethesda, MD Mary Horowitz (ex-officio) CIBMTR - ([email protected]) Milwaukee, WI Brent Logan (ex-officio) CIBMTR - ([email protected]) Milwaukee, WI Adam Mendizabal (ex-officio) The Emmes Corporation - ([email protected]) Rockville, MD Marlene Peters-Lawrence (ex-officio) National Heart, Lung, and Blood Institute, NIH ([email protected]) Bethesda, MD

172

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 Attachment A6: Toxicity and Supportive Care Committee Roster

Attachment A6: Toxicity and Supportive Care Committee Roster Term Name Organization Expiration Mark Litzow Mayo Clinic 2019 ([email protected]) Rochester, MN Matt Lunning University of Nebraska 2019 ([email protected]) Omaha, NE Anita D'Souza Medical College of Wisconsin 2018 ([email protected]) Milwaukee, WI Chris Dvorak University of California, San Francisco 2018 ([email protected]) San Francisco, CA Shin Mineishi University of Alabama at Birmingham 2018 ([email protected]) Birmingham, AL Celalettin Ustun University of Minnesota 2018 ([email protected]) Minneapolis, MN Leona Holmberg Fred Hutchinson Cancer Research Center 2017 ([email protected]) Seattle, WA Hillard Lazarus (Chair) Case Western Reserve University 2017 ([email protected]) Cleveland, OH Andrew Rezvani Stanford University 2017 ([email protected]) Palo Alto, CA Greg Yanik University of Michigan 2017 ([email protected]) Ann Arbor, MI Mary Horowitz (ex-officio) CIBMTR - ([email protected]) Milwaukee, WI Adam Mendizabal (ex-officio) The Emmes Corporation - ([email protected]) Rockville, MD

173

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 Attachment A7: Publications, Abstracts, and Presentations Committee Roster

Attachment A7: Publications, Abstracts, and Presentations Committee Roster Term Name Organization Expiration Sid Ganguly University of Kansas Medical Center 2019 ([email protected]) Westwood, KS Joseph Pidala H. Lee Moffitt Cancer Center 2019 ([email protected]) Tampa, FL Stella Davies (Co-Chair) Cincinnati Children’s 2018 ([email protected]) Cincinnati, OH Parameswaran Hari Medical College of Wisconsin 2018 ([email protected]) Milwaukee, WI Paul O'Donnell Massachusetts General Hospital 2018 ([email protected]) Boston, MA Asad Bashey (Co-Chair) Northside Hospital 2017 ([email protected]) Atlanta, GA Dennis Confer (ex-officio) NMDP/Be The Match - ([email protected]) Minneapolis, MN Nancy Geller (ex-officio) National Heart, Lung, and Blood Institute, NIH - ([email protected]) Bethesda, MD Mary Horowitz (ex-officio) CIBMTR - ([email protected]) Milwaukee, WI Adam Mendizabal (ex-officio) The Emmes Corporation - ([email protected]) Rockville, MD William Merritt (ex-officio) National Cancer Institute, NIH - ([email protected]) Bethesda, MD Nancy Poland (ex-officio) CIBMTR - ([email protected]) Minneapolis, MN

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 Attachment B1: Publications

Attachment B: Publications, Abstracts, and Presentations Attachment B1: Publications by Year

Protocol Number Publication PMCID Number

2004

Wingard JR. Design issues in a prospective randomized double- BMT CTN 0101 N/A blinded trial of prophylaxis with fluconazole versus (pre-dates PMCID 1 voriconazole after allogeneic hematopoietic cell requirements) transplantation. Clinical Infectious Disease. 2004 Oct 15; 39 Suppl 4:S176-180.

2005

Logan BR. Optimal two-stage randomized Phase II clinical trials. BMT CTN 0302 N/A 2 Clinical Trials. 2005 Feb 1; 2(1):5-12. (pre-dates PMCID requirements) Ho VT, Cutler C, Carter S, Martin P, Adams R, Horowitz M, Network N/A Ferrara J, Soiffer R, Giralt S. BMT CTN Toxicity Committee publication (pre-dates PMCID 3 consensus summary, thrombotic microangiopathy after requirements) hematopoietic stem cell transplantation. Biology of Blood and Marrow Transplantation. 2005 Aug 1; 11(8):571-575.

2007

Keating K. Editorial: Prospective clinical trials in BMT come of Network N/A age in the US: The Blood and Marrow Transplant Clinical Trials publication (pre-dates PMCID 4 Network. Biology of Blood and Marrow Transplantation. 2007 requirements) Mar 1, 13(3):255-256. Weisdorf D, Carter S, Confer D, Ferrara J, Horowitz M. Blood Network N/A and Marrow Transplant Clinical Trials Network (BMT CTN): publication (pre-dates PMCID 5 Addressing unanswered questions. Biology of Blood and requirements) Marrow Transplantation. 2007 Mar 1; 13(3):257-262. Ferrara J, Anasetti C, Stadtmauer E, Antin J, Wingard J, Lee SJ, Network N/A Levine J, Schultz K, Appelbaum F, Negrin R, Giralt S, Bredeson C, publication (pre-dates PMCID 6 Heslop H, Horowitz M. BMT CTN State of the Science requirements) Symposium 2007. Biology of Blood and Marrow Transplantation. 2007 Nov 1; 13:1268-1285.

2008

Logan B, Leifer E, Bredeson C, Horowitz M, Ewell M, Carter S, BMT CTN 0102 PMC2671015 Geller N. Use of biological assignment in hematopoietic stem 7 cell transplantation clinical trials. Clinical Trials. 2008 Jan 1; 5(6):607-616.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 Attachment B1: Publications

Protocol Number Publication PMCID Number Cutler C, Stevenson K, Kim HT, Richardson P, Ho VT, Linden E, BMT CTN 0402 PMC2597119 Revta C, Ebert R, Warren D, Choi S, Koreth J, Armand P, Alyea E, Carter S, Horowitz M, Antin JH, Soiffer R. Sirolimus is associated 8 with veno-occlusive disease of the liver after myeloablative allogeneic stem cell transplantation. Blood. 2008 Dec 1; 112(12):4425-4431. Epub 2008 Sep 5.

2009

Alousi A, Weisdorf D, Logan B, Bolaños-Meade J, Carter S, BMT CTN 0302 PMC2713466 DiFronzo N, Pasquini M, Goldstein S, Ho V, Hayes-Lattin B, PRIMARY Wingard J, Horowitz M, Levine J. Etanercept, mycophenolate, MANUSCRIPT 9 denileukin or pentostatin plus corticosteroids for acute graft- versus-host disease: A randomized Phase 2 trial from the Blood and Marrow Transplant Clinical Trials Network. Blood. 2009 Jul 16; 114(3):511-517. Epub 2009 May 14. Giralt S, Vesole DH, Somlo G, Krishnan A, Stadtmauer E, BMT CTN 0102 N/A McCarthy P, Pasquini MC, BMT CTN Multiple Myeloma Working Correspondence Group. Re: Tandem versus single autologous hematopoietic cell transplantation for the treatment of multiple myeloma: A 10 systematic review and meta-analysis. Journal of the National Cancer Institute. 2009 Jul 01; 101(13):964; author reply 966- 967. Epub 2009 Jun 17. [Comment on: Journal of the National Cancer Institute 101(2):100-106, 2009].

2010

Jacobson PA, Huang J, Wu J, Kim M, Logan B, Alousi A, Grimley BMT CTN 0302 PMC3104501 M, Bolaños-Meade J, Ho V, Levine JE, Weisdorf D. Mycophenolate pharmacokinetics and association with 11 response to acute graft-versus-host disease treatment from the Blood and Marrow Transplant Clinical Trials Network. Biology of Blood and Marrow Transplantation. 2010 Mar 1; 16(3):421-429. Levine JE, Logan B, Wu J, Alousi AM, Ho V, Bolaños-Meade J, BMT CTN 0302 PMC2955996 Weisdorf D, On behalf of the BMT CTN. Graft-versus-host 12 disease treatment: predictors of survival. Biology of Blood and Marrow Transplantation. 2010 Dec 1; 16(12):1693-1699. Epub 2010 Jun 9.

176

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 Attachment B1: Publications

Protocol Number Publication PMCID Number Wingard JR, Carter SL, Walsh TJ, Kurtzberg J, Small TN, Baden BMT CTN 0101 PMC3012532 LR, Gersten ID, Mendizabal AM, Leather HL, Confer DL, Maziarz PRIMARY RT, Stadtmauer EA, Bolaños-Meade J, Brown J, DiPersio JF, MANUSCRIPT Boeckh M, Marr KA; BMT CTN. Randomized double-blind trial 13 of fluconazole versus voriconazole for prevention of invasive fungal infection after allogeneic hematopoietic cell transplantation. Blood. 2010 Dec 9; 116(24):5111-5118. Epub 2010 Sep 8. Pulsipher MA, Young NS, Tolar J, Risitano AM, Deeg HJ, BMT CTN 0301 PMC3053041 Anderlini P, Calado R, Kojima S, Eapen M, Harris R, Scheinberg P, Savage S, Maciejewski JP, Tiu RV, DiFronzo N, Horowitz MM, Antin JH. Optimization of therapy for severe aplastic anemia 14 based on clinical, biological and treatment response parameters: conclusions of an international working group on severe aplastic anemia convened by the BMT CTN, March 2010. Biology of Blood and Marrow Transplantation. 2011 Mar 1; 17(3):291-299. Epub 2010 Oct 27. Tomblyn MR, Ewell M, Bredeson C, Kahl BS, Goodman SA, BMT CTN 0202 PMC3114272 Horowitz MM, Vose JM, Negrin RS, Laport GG. Autologous PRIMARY versus reduced intensity allogeneic hematopoietic cell MANUSCRIPT 15 transplantation for patients with chemosensitive follicular non- Hodgkin lymphoma beyond first complete response or first partial response. Biology of Blood and Marrow Transplantation. 2011 Jul 1; 17(7):1051-1057. Epub 2010 Nov 10.

Horwitz EM, Horowitz MM, DiFronzo NL, Kohn DB, Heslop HE, Network PMC3387575 BMT CTN State of the Science Cell and Gene Therapy publication Committee. Guidance for developing Phase II cell therapy trial 16 proposals for consideration by the BMT CTN. Biology of Blood and Marrow Transplantation. 2011 Feb 1; 17(2):192-196. Epub 2010 Dec 21.

2011

Devine SM, Carter S, Soiffer RJ, Pasquini MC, Hari PN, Stein A, BMT CTN 0303 PMC3150599 Lazarus HM, Linker C, Stadtmauer EA, Alyea EP 3rd, Keever- PRIMARY Taylor CA, O'Reilly RJ. Low risk of chronic graft-versus-host MANUSCRIPT disease and relapse associated with T cell depleted peripheral 17 blood stem cell transplantation for acute myeloid leukemia in first remission: results of the Blood and Marrow Transplant Clinical Trials Network protocol 0303. Biology of Blood and Marrow Transplantation. 2011 Sep 1; 17(9):1343-1351. Epub 2011 Feb 12.

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Protocol Number Publication PMCID Number Kohn DB, Dotti G, Brentjens R, Savoldo B, Jensen M, Cooper LJ, Network PMC3048197 June C, Rosenberg S, Sadelain M, Heslop HE. CARs on track in publication the clinic: Workshop of the Blood and Marrow Transplant 18 Clinical Trials Network sub-committee on cell and gene therapy. Molecular Therapy. 2011 Mar 1; 19(3):432-438. Epub 2011 Mar 1. Brunstein CG, Fuchs EJ, Carter SL, Karanes C, Costa LJ, Wu J, BMT CTN 0603 / PMC3138683 Devine SM, Wingard JR, Aljitawi OS, Cutler CS, Jagasia MH, BMT CTN 0604 Ballen KK, Eapen M, O'Donnell PV. Alternative donor PRIMARY 19 transplantation after reduced intensity conditioning: results of MANUSCRIPT parallel Phase 2 trials using HLA-mismatched related bone marrow or unrelated umbilical cord blood grafts. Blood. 2011 Jul 14; 118(2):282-288. Epub 2011 Apr 28. Denzen EM, Burton Santibáñez ME, Moore H, Foley A, Gersten Network PMC3242929 I, Gurgol C, Majhail NS, Spellecy R, Horowitz MM, Murphy EA. publication 20 Easy-to-read informed consent forms for hematopoietic cell transplantation clinical trials. Biology of Blood and Marrow Transplantation. 2012 Feb 1; 18(2):183–189. Epub 2011 Jul 30. Keever-Taylor CA, Devine SM, Soiffer RJ, Mendizabal A, Carter BMT CTN 0303 PMC3762249 S, Pasquini MC, Hari PN, Stein A, Lazarus HM, Linker C, Goldstein SC, Stadtmauer EA, O'Reilly RJ. Characteristics of CliniMACS(®) System CD34-enriched T cell-depleted grafts in a 21 multicenter trial for acute myeloid leukemia- Blood and Marrow Transplant Clinical Trials Network (BMT CTN) protocol 0303. Biology of Blood and Marrow Transplantation. 2012 May 1; 18(5):690-697. Epub 2011 Aug 26. Krishnan A, Pasquini MC, Logan B, Stadtmauer EA, Vesole DH, BMT CTN 0102 PMC3611089 Alyea E 3rd, Antin JH, Comenzo R, Goodman S, Hari P, Laport G, PRIMARY Qazilbash MH, Rowley S, Sahebi F, Somlo G, Vogl DT, Weisdorf MANUSCRIPT D, Ewell M, Wu J, Geller NL, Horowitz MM, Giralt S, Maloney 22 DG. Autologous haemopoietic stem-cell transplantation followed by allogeneic or autologous haemopoietic stem-cell transplantation in patients with multiple myeloma (BMT CTN 0102): A Phase 3 biological assignment trial. Lancet Oncology. 2011 Dec 1; 12(13):1195-1203. Epub 2011 Sep 29.

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Protocol Number Publication PMCID Number

2012

Kamani NR, Walters MC, Carter S, Aquino V, Brochstein JA, BMT CTN 0601 PMC3618440 Chaudhury S, Eapen M, Freed BM, Grimley M, Levine JE, Logan B, Moore T, Panepinto J, Parikh S, Pulsipher MA, Sande J, Schultz KR, Spellman S, Shenoy S. Unrelated donor cord blood 23 transplantation for children with severe sickle cell disease: results of one cohort from the Phase II study from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN). Biology of Blood and Marrow Transplantation. 2012 Aug 1; 18(8):1265-1272. Epub 2012 Feb 16. Levine J, Logan BR, Wu J, Alousi AM, Bolaños-Meade J, Ferrara BMT CTN 0302 PMC3335389 JLM, Ho VT, Weisdorf DJ, Paczesny S. Acute graft-versus-host disease biomarkers measured during therapy can predict 24 treatment outcomes: A Blood and Marrow Transplant Clinical Trials Network study. Blood. 2012 Apr 19; 119(16):3854-3860. Epub 2012 Mar 1. Tolar J, Deeg HJ, Arai S, Horwitz M, Antin JH, McCarty J, Adams BMT CTN 0301 PMC3677744 R, Ewell M, Leifer E, Gersten I, Carter S, Horowitz MM, Nakamura R, Pulsipher MA, DiFronzo NL, Confer DL, Eapen M, Anderlini P. Fludarabine-based conditioning for marrow transplantation from unrelated donors in severe aplastic 25 anemia: early results of a cyclophosphamide dose deescalation study show life-threatening adverse events at predefined cyclophosphamide dose levels. Biology of Blood and Marrow Transplantation. 2012 July 1; 18(7):1007-1011. Epub 2012 Apr 27. McCarthy PL, Owzar K, Hofmeister CC, Hurd DD, Hassoun H, BMT CTN 0704 / PMC3744390 Richardson PG, Giralt S, Stadtmauer EA, Weisdorf DJ, Vij R, CALGB 100104 / Moreb JS, Callander NS, Van Besien K, Gentile T, Isola L, Maziarz ECOG 100104 RT, Gabriel DA, Bashey A, Landau H, Martin T, Qazilbash MH, PRIMARY Levitan D, McClune B, Schlossman R, Hars V, Postiglione J, Jiang MANUSCRIPT 26 C, Bennett E, Barry S, Bressler L, Kelly M, Sexton M, Rosenbaum C, Hari P, Pasquini MC, Horowitz MM, Shea TC, Devine SM, Anderson KC, Linker C. Lenalidomide after stem-cell transplantation for multiple myeloma. New England Journal of Medicine. 2012 May 10; 366(19):1770-1781.

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Protocol Number Publication PMCID Number Pasquini M, Devine S, Mendizabal A, Baden L, Wingard J, BMT CTN 0303 PMC3434978 Lazarus H, Appelbaum F, Keever-Taylor C, Horowitz M, Carter S, O’Reilly R, Soiffer R. Comparative outcomes of donor graft CD34+ selection and immune suppressive therapy as graft- 27 versus-host disease prophylaxis for patients with acute myeloid leukemia in complete remission undergoing HLA-matched sibling allogeneic hematopoietic cell transplantation. Journal of Clinical Oncology. 2012 Sep 10; 30(26):3194-3201. Epub 2012 Aug 6. Logan BR, Zhang MJ. The use of group sequential designs with Network PMC3574186 28 common competing risks tests. Statistics in Medicine. 2013 Mar publication 15; 32(6):899-913. Epub 2012 Sep 4.

Foley B, Cooley S, Verneris MR, Curtsinger J, Luo X, Waller EK, BMT CTN 0201 PMC3490031 Anasetti C, Weisdorf D, Miller JS. Human cytomegalovirus (CMV)-induced memory-like NKG2C(+) NK cells are 29 transplantable and expand in vivo in response to recipient CMV antigen. Journal of Immunology. 2012 Nov 15; 189(10):5082- 5088. Epub 2012 Oct 17. Anasetti C, Logan BR, Lee SJ, Waller EK, Weisdorf DJ, Wingard BMT CTN 0201 PMC3816375 JR, Cutler CS, Westervelt P, Woolfrey A, Couban S, Ehninger G, PRIMARY Johnston L, Maziarz RT, Pulsipher MA, Porter DL, Mineishi S, MANUSCRIPT McCarty JM, Khan SP, Anderlini P, Bensinger WI, Leitman SF, 30 Rowley SD, Bredeson C, Carter SL, Horowitz MM, Confer DL; Blood and Marrow Transplant Clinical Trials Network. Peripheral blood stem cells versus bone marrow from unrelated donors. New England Journal of Medicine. 2012 Oct 18; 367(16):1487-1496. Bolaños-Meade J, Wu J, Logan BR, Levine JE, Ho VT, Alousi AM, BMT CTN 0302 PMC3653300 Weisdorf DJ, Luznik L. Lymphocyte phenotype during therapy 31 for acute graft-versus-host disease: a brief report from BMT- CTN 0302. Biology of Blood and Marrow Transplantation. 2013 Mar 1; 19(3):481-485. Epub 2012 Dec 12.

2013

Vose JM, Carter S, Burns LJ, Ayala E, Press O, Moskowitz CH, BMT CTN 0401 PMC3635682 Stadtmauer EA, Mineishi S, Ambinder RF, Fenske TS, Horowitz PRIMARY MM, Fisher RI, Tomblyn M. Phase III randomized study of MANUSCRIPT rituximab/carmustine, etoposide, cytarabine, melphalan 32 (BEAM) compared with Iodine-131 tositumomab/BEAM with autologous hematopoietic cell transplantation for relapsed diffuse large B-cell lymphoma: results from the BMT CTN trial. Journal of Clinical Oncology. 2013 May 1; 31(13):1662-1668. Epub 2013 Mar 11.

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Protocol Number Publication PMCID Number Giralt S, McCarthy PL, Anderson KC, Carter SL, Richardson PG, BMT CTN 0704 / N/A Rajkumar SV, Laport GG, Stadtmauer EA, Pasquini MC, CALGB 100104 / Horowitz MM. Anatomy of a successful practice-changing ECOG 100104 33 study: A Blood and Marrow Transplant Clinical Trials Network- National Cancer Institute Cooperative Group Collaboration. Biology of Blood and Marrow Transplantation. 2013 Jun 01; 19(6)858-859. Epub 2013 Mar 29. Mauskopf J, Chirila C, Graham J, Gersten I, Maziarz R, Baden L, BMT CTN 0101 PMC4019750 Bolaños-Meade J, Brown J, Walsh T, Horowitz M, Kurtzberg J, Marr K, Wingard J, Leather H. Cost-effectiveness analysis of 34 voriconazole compared with fluconazole for prevention of invasive fungal infection in patients receiving allogeneic hematopoietic cell transplants. American Journal Health- System Pharmacy. 2013 Sep 1; 70(17):1518-1527. Switzer GE, Bruce JG, Harrington D, Haagenson M, Drexler R, BMT CTN 0201 PMC3978600 Foley A, Confer D, Bishop M, Anderlini P, Rowley S, Leitman SF, Anasetti C, Wingard JR. Health-related QoL of bone marrow 35 versus PBSC donors: a pre-specified subgroup analysis from a phase III RCT BMT CTN protocol 0201. Biology of Blood and Marrow Transplantation. 2014 Jan 1; 20(1):118-127. Epub 2013 Nov 1. Ferrara J. Blood and Marrow Transplant Clinical Trials Network: Network PMC24239651 Progress since the State of the Science Symposium 2007. publication 36 Biology of Blood and Marrow Transplantation. 2014 Feb 1; 20(2):149-153. Epub 2013 Nov 12.

2014

Roth JA, Bensink ME, O’Donnell PV, Fuchs EJ, Eapen M, Ramsey BMT CTN 1101 PMC4036637 SD. Design of a cost -effectiveness analysis alongside a randomized trial of transplantation using umbilical cord blood 37 versus HLA-haploidentical related bone marrow in advanced hematologic cancer. Journal of Comparative Effectiveness Research. 2014 Mar 1; 3(2):135-144. Atallah E, Bylow K, Troy J, Saber W. Treatment of older patients BMT CTN 1102 PMC4031643 with high-risk myelodysplastic syndromes (MDS): The emerging 38 role of allogeneic hematopoietic stem cell transplantation (Allo HSCT). Current Hematologic Malignancy Reports. 2014 Mar 1; 9(1):57-65.

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Protocol Number Publication PMCID Number Yanik GA, Horowitz MM, Weisdorf DJ, Logan BR, Ho VT, Soiffer BMT CTN 0403 PMC4128626 RJ, Carter SL, Wu J, Wingard JR, DiFronzo NL, Ferrara JL, Giralt S, PRIMARY Madtes DK, Drexler R, White ES, Cooke KR. Randomized, MANUSCRIPT double-blind, placebo-controlled trial of soluble tumor necrosis 39 factor receptor: Enbrel (etanercept) for the treatment of idiopathic pneumonia syndrome following allogeneic stem cell transplantation: Blood and Marrow Transplant Clinical Trials Network protocol. Biology of Blood and Marrow Transplantation. 2014 Jun 1; 20(6):858-864. Epub 2014 Mar 7. Eapen M, O’Donnell P, Brunstein C, Wu J, Barowski K, BMT CTN PMC4163123 Mendizabal A, Fuchs E. Mismatched related and unrelated 0603 / 0604 and donors for allogeneic hematopoietic cell transplantation for 1101 40 adults with hematologic malignancies. Biology of Blood and Marrow Transplantation. 2014 Oct 1; 20(10):1485-1492. Epub 2014 May 23. Jacobsen PB, Le-Rademacher J, Jim H, Syrjala K, Wingard JR, BMT CTN 0902 PMC4163109 Logan B, Wu J, Majhail NS, Wood W, Rizzo JD, Geller NL, Kitko PRIMARY C, Faber E, Abidi MH, Slater S, Horowitz MM, Lee SJ. Exercise MANUSCRIPT and stress management training prior to hematopoietic cell 41 transplantation: Blood and Marrow Transplant Clinical Trial Network (BMT CTN) 0902. Biology of Blood and Marrow Transplantation. 2014 Oct 1; 20(10):1530-1536. Epub 2014 Jun 6. Saber W, Le-Rademacher J, Sekeres M, Logan B, Lewis M, BMT CTN 1102 PMC4169902 Mendizabal A, Leifer E, Appelbaum F, Horowitz M, Nakamura R, Cutler C. Multicenter biologic assignment trial comparing reduced-intensity allogeneic hematopoietic cell transplant to hypomethylating therapy or best supportive care in patients 42 aged 50 to 75 with intermediate-2 and high-risk myelodysplastic syndrome: Blood and Marrow Transplant Clinical Trials Network #1102 study rationale, design, and methods. Biology of Blood and Marrow Transplantation. 2014 Oct 1; 20(10):1566-1572. Epub 2014 Jun 24. Waller EK, Logan BR, Harris WA, Devine SM, Porter DL, Mineishi BMT CTN 0201 PMC4180368 M, McCarty JM, Gonzalez CE, Spitzer TR, Krijanovski OI, Linenberger ML, Woolfrey A, Howard A, Wu J, Confer DL, Anasetti A. Improved survival after transplantation of more 43 donor plasmacytoid dendritic or naïve T cells from unrelated- donor marrow grafts: results from BMT CTN 0201. Journal of Clinical Oncology. 2014 Aug 1; 32(22):2365-2372. Epub 2014 Jun 30.

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Protocol Number Publication PMCID Number Cutler C, Logan B, Nakamura R, Johnston L, Choi S, Porter D, BMT CTN 0402 PMC4141519 Hogan W, Pasquini M, MacMillan M, Hsu J, Waller E, Grupp S, PRIMARY McCarthy P, Wu J, Hu Z, Carter S, Horowitz M, Antin J. MANUSCRIPT 44 Tacrolimus / sirolimus versus tacrolimus / methotrexate as GVHD prophylaxis after matched, related donor allogeneic HCT. Blood. 2014 Aug 21; 124(8):1372-1377. Epub 2014 Jun 30. Bolaños-Meade J, Logan BR, Alousi AM, Antin JH, Barowski K, BMT CTN 0802 PMC4239331 Carter SL, Goldstein SC, Hexner EO, Horowitz MM, Lee SJ, PRIMARY Levine JE, MacMillan ML, Martin PJ, Mendizabal AM, Nakamura MANUSCRIPT 45 R, Pasquini MC, Weisdorf DJ, Westervelt P, Ho VT. Phase 3 clinical trial of steroids / mycophenolate mofetil vs steroids / placebo as therapy for acute GVHD: BMT CTN 0802. Blood. 2014 Nov 20; 124(22):3221-3227. Epub 2014 Aug 28. Howard A, Fernandez-Vina MA, Appelbaum FR, Confer DL, Network PMC4272893 Devine SM, Horowitz MM, Mendizabal A, Laport GG, Pasquini publication MC, Spellman SR. Recommendations for donor human leukocyte antigen assessment and matching for allogeneic stem 46 cell transplantation: consensus opinion of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN). Biology of Blood and Marrow Transplantation. 2015 Jan 1; 21(1):4-7. Epub 2014 Sep 30. Appelbaum F, Anasetti C, Antin J, Atkins H, Davies S, Devine S, Network PMC4426907 Giralt S, Heslop H, Laport G, Lee S, Logan B, Pasquini M, publication Pulsipher M, Stadtmauer E, Wingard J, Horowitz M. Blood and 47 Marrow Transplant Clinical Trials Network State of the Science Symposium 2014. Biology of Blood and Marrow Transplantation. 2015 Feb 1; 21(2):202-224. Epub 2014 Oct 15. Wagner JE Jr, Eapen M, Carter S, Wang Y, Schultz KR, Wall DA, BMT CTN 0501 PMC4257059 Bunin N, Delaney C, Haut P, Margolis D, Peres E, Verneris MR, PRIMARY 48 Walters M, Horowitz MM, Kurtzberg J. One-unit versus two- MANUSCRIPT unit cord-blood transplant for hematologic cancers. New England Journal of Medicine. 2014 Oct 30; 371(18):1685-1694. Levine JE, Braun TM, Harris AC, Holler E, Taylor A, Miller H, BMT CTN 0302 PMC4340092 Magenau J, Weisdorf DJ, Ho VT, Bolaños-Meade J, Alousi AM, Ferrara JL, Blood and Marrow Transplant Clinical Trials 49 Network. A prognostic score for acute graft-versus-host disease based on biomarkers: A multicentre study. Lancet Haematology. 2015 Jan 1; 2(1):e21-29. Epub 2014 Dec 23.

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Protocol Number Publication PMCID Number

2015

MacMillan ML, Robin M, Harris AC, DeFor TE, Martin PJ, Alousi BMT CTN 0302 PMC4359643 A, Ho VT, Bolaños-Meade J, Ferrara JLM, Jones R, Arora M, and 0802 Blazar, BR, Holtan SG, Jacobsohn D, Pasquini M, Socie G, Antin JH, Levine JE, Weisdorf DJ. A refined risk score for acute graft- 50 versus-host disease that predicts response to initial therapy, survival, and transplant-related mortality. Biology of Blood and Marrow Transplantation. 2015 Apr 1; 21(4):761-767. Epub 2015 Jan 10. Holtan SG, Verneris MR, Schultz KR, Newell LF, Meyers G, He F, BMT CTN 0302 PMC4426052 DeFor TE, Vercellotti GM, Slungaard A, MacMillan ML, Cooley and 0802 SA, Blazar BR, Panoskaltsis-Mortari A, Weisdorf DJ. Circulating angiogenic factors associated with response and survival in 51 patients with acute graft-versus-host disease: Results from Blood and Marrow Transplant Clinical Trials Network 0302 and 0802. Biology of Blood and Marrow Transplantation. 2015 Jun 1; 21(6):1029-1036. Epub 2015 Mar 7. Khera N, Majhail NS, Brazauskas R, Wang Z, He N, Aljurf MD, BMT CTN 0201 PMC4568172 Akpek G, Atsuta Y, Beattie S, Bredeson CN, Burns LJ, Dalal JD, Freytes CO, Gupta V, Inamoto Y, Lazarus HM, LeMaistre CF, Steinberg A, Szwajcer D, Wingard JR, Wirk B, Wood WA, Joffe S, Hahn TE, Loberiza FR, Anasetti C, Horowitz MM, Lee SJ. 52 Comparison of characteristics and outcomes of trial participants and nonparticipants: Example of Blood and Marrow Transplant Clinical Trials Network 0201 trial. Biology of Blood and Marrow Transplantation. 2015 Oct 1; 21(10):1815- 1822. Epub 2015 Jun 11. Anderlini P, Wu J, Gersten I, Ewell M, Tolar J, Antin JH, Adams R, BMT CTN 0301 PMC4861234 Arai S, Eames G, Horwitz ME, McCarty J, Nakamura R, Pulsipher PRIMARY MA, Rowley S, Leifer E, Carter SL, DiFronzo NL, Horowitz MM, MANUSCRIPT 53 Confer D, Deeg HJ, Eapen M. Cyclophosphamide conditioning in patients with severe aplastic anaemia given unrelated marrow transplantation: a phase 1-2 dose de-escalation study. Lancet Haematology. 2015 Sep 1; 2(9):e367-375. Epub 2015 Sep 2. Young JH, Logan BR, Wu J, Wingard JR, Weisdorf DJ, Mudrick C, BMT CTN 0201 PMC4716871 Knust K, Horowitz MM, Confer DL, Dubberke ER, Pergam SA, Marty FM, Strasfeld LM, Brown JWM, Langston AA, Schuster MG, Kaul DR, Martin SI, Anasetti C, Blood and Marrow 54 Transplant Clinical Trials Network Trial 0201. Infections after transplantation of bone marrow or peripheral-blood stem cells from unrelated donors. Biology of Blood and Marrow Transplantation. 2016 Feb 1; 22(2):359-370. Epub 2015 Sep 25.

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Protocol Number Publication PMCID Number Giralt S, Garderet L, Durie B, Cook G, Gahrton G, Bruno B, Hari Network PMC4757494 P, Lokhorst H, McCarthy P, Krishnan A, Sonneveld P, publication Goldschmidt H, Jagannath S, Barlogie B, Mateos M, Gimsing P, Sezer O, Mikhael J, Lu J, Dimopoulos M, Mazumder A, Palumbo A, Abonour R, Anderson K, Attal M, Blade J, Bird J, Cavo M, Comenzo R, de la Rubia J, Einsele H, Garcia-Sanz R, Hillengass J, Holstein S, Johnsen HE, Joshua D, Koehne G, Kumar S, Kyle R, Leleu X, Lonial S, Ludwig H, Nahi H, Nooka A, Orlowski R, Rajkumar V, Reiman A, Richardson P, Riva E, San Miguel J, Turreson I, Usmani S, Vesole D, Bensinger W, Qazilbash M, 55 Efebera Y, Mohty M, Gasparreto C, Gajewski J, LeMaistre CF, Bredeson C, Moreau P, Pasquini M, Kroeger N, Stadtmauer E. American Society of Blood and Marrow Transplantation, European Society of Blood and Marrow Transplantation, Blood and Marrow Transplant Clinical Trials Network, and International Myeloma Working Group Consensus Conference on Salvage Hematopoietic Cell Transplantation in Patients with Relapsed Multiple Myeloma. Biology of Blood and Marrow Transplantation. 2015 Dec 1; 21(12):2039-2051. Epub 2015 Sep 30. Wood WA, Le-Rademacher J, Syrjala KL, Jim H, Jacobsen PB, BMT CTN 0902 PMC4707096 Knight JM, Abidi MH, Wingard JR, Majhail NS, Geller NL, Rizzo JD, Fei M, Wu J, Horowitz MM, Lee SJ. Patient-reported physical 56 functioning predicts the success of hematopoietic cell transplantation (BMT CTN 0902). Cancer. 2016 Jan 1; 122(1):91- 98. Epub 2015 Oct 6. Devine SM, Owzar K, Blum W, Mulkey F, Stone RM, Hsu JW, CALGB 100103 / PMC4658453 Champlin RE, Chen YB, Vij R, Slack J, Soiffer RJ, Larson RA, Shea BMT CTN 0502 TC, Hars V, Sibley AB, Giralt S, Carter S, Horowitz MM, Linker C, PRIMARY Alyea EP. Phase II study of allogeneic transplantation for older MANUSCRIPT patients with acute myeloid leukemia in first complete 57 remission using a reduced-intensity conditioning regimen: Results from Cancer and Leukemia Group B 100103 (Alliance for Clinical Trials in Oncology) / Blood and Marrow Transplant Clinical Trial Network 0502. Journal of Clinical Oncology. 2015 Dec 10; 33(35):4167-4175. Epub 2015 Nov 2.

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Protocol Number Publication PMCID Number

2016

Burns LJ, Logan BR, Chitphakdithai P, Miller JP, Drexler R, BMT CTN 0201 PMC4867293 Spellman S, Switzer GE, Wingard JR, Anasetti C, Confer DL, (Available Blood and Marrow Transplant Clinical Trials Network. Recovery June 1, 2017) of unrelated donors of peripheral blood stem cells versus 58 recovery of unrelated donors of bone marrow: A prespecified analysis from the Phase III Blood and Marrow Transplant Clinical Trials Network protocol 0201. Biology of Blood and Marrow Transplantation. 2016 Jun 1; 22(6):1108-1116. Epub 2016 Mar 21. Laport GG, Wu J, Logan B, Bachanova V, Hosing C, Fenske T, BMT CTN 0701 PMC4949103 Longo W, Devine SM, Nademanee A, Gersten I, Horowitz M, PRIMARY (Available Lazarus HM, Riches ML. Reduced-intensity conditioning with MANUSCRIPT August 1, 2017) fludarabine, cyclophosphamide, and high-dose rituximab for 59 allogeneic hematopoietic cell transplantation for follicular lymphoma: A Phase Two multicenter trial from the Blood and Marrow Transplant Clinical Trials Network. Biology of Blood Marrow Transplantation. 2016 Aug 1; 22(8):1440-1448. Epub 2016 Apr 23. Hope W, Walsh T, Goodwin J, Peloquin C, Howard A, BMT CTN 0101 PMC4954923 Kurtzberg J, Mendizabal A, Confer D, Bulitta J, Baden L, Neely (Available M, Wingard J. Voriconazole pharmacokinetics following August 1, 2017) 60 hematopoietic stem cell transplantation: Results from the BMT CTN 0101 trial. Journal of Antimicrobial Chemotherapy. 2016 Aug 1; 71(8):2234-2240. Epub 2016 Apr 27. D'Souza A, Pasquini M, Logan B, Giralt S, Krishnan A, Antin J, BMT CTN 0102 PMC5154782 Howard A, Goodman S, Qazilbash M, Knust K, Sahebi F, (Available Weisdorf D, Vesole D, Vesole D, Stadtmauer E, Maloney D, December 13, 61 Parameswaran H. Heavy / light chain ratio normalization prior 2017) to transplant is of independent prognostic significance in multiple myeloma: A BMT CTN 0102 correlative study. British Journal of Haematology. 2016 Jun 13. [Epub ahead of print]. Alvarnas JC, Le-Rademacher J, Wang Y, Little RF, Akpek G, BMT CTN 0803 PMC5000843 Ayala E, Devine S, Baiocchi R, Lozanski G, Kaplan L, Noy A, PRIMARY (Available Popat U, Hsu J, Morris LE Jr, Thompson J, Horowitz MM, MANUSCRIPT August 25, 2017) Mendizabal A, Levine A, Krishnan A, Forman SJ, Navarro WH, 62 Ambinder R. Autologous hematopoietic cell transplantation for HIV-related lymphoma: Results of the BMT CTN 0803 / AMC 071 trial. Blood. 2016 Aug 25; 128(8):1050-1058. Epub 2016 Jun 13.

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Protocol Number Publication PMCID Number Steering Committee of the Blood and Marrow Transplant Network PMC5027144 Clinical Trials Network. The Blood and Marrow Transplant 10 Year (Available Clinical Trials Network: An effective infrastructure for Publication October 1, 2017) 63 addressing important issues in hematopoietic cell transplantation. Biology of Blood and Marrow Transplantation. 2016 Oct 1; 22(10):1747-1457. Epub 2016 Jul 11. Lee SJ, Logan B, Westervelt P, Cutler C, Woolfrey A, Khan SP, BMT CTN 0201 PMC5145732 Waller EK, Maziarz RT, Wu J, Shaw B, Confer D, Horowitz MM, (Available Anasetti C. Comparison of patient-reported outcomes in 5- December 1, 2017) 64 year survivors who received bone marrow vs peripheral blood unrelated donor transplantation: Long-term follow-up of a randomized clinical trial. JAMA Oncology. 2016 Dec 1; 2(12):1583-1589. Epub 2016 Aug 11. Jim HSL, Sutton SK, Small BJ, Jacobsen PB, Wood WA, Knight BMT CTN 0902 PMC5068568 JM, Majhail NS, Syrjala KL, Lee SJ. Trajectories of quality of life (Available after hematopoietic cell transplantation: Secondary analysis November 1, 2017) 65 of Blood and Marrow Transplant Clinical Trials Network 0902 data. Biology of Blood and Marrow Transplantation. 2016 Nov 1; 22(11):2077-2083. Epub 2016 Aug 15. O'Donnell PV, Eapen M, Horowitz MM, Logan BR, DiGilio A, BMT CTN 0603 PMC5143194 Brunstein C, Fuchs E, Flowers ME, Salit R, Raj K, Pagliuca A, (Available Bradstock K, Granata A, Castagna L, Fürst S, Blaise D. December 1, 2017) Comparable outcomes with marrow or peripheral blood as 66 stem cell sources for hematopoietic cell transplantation from haploidentical donors after non-ablative conditioning: A matched-pair analysis. Bone Marrow Transplantation. 2016 Dec 1; 51(12):1599-1601. Epub 2016 Aug 15. Knight JM, Syrjala KL, Majhail NS, Martens M, Le-Rademacher BMT CTN 0902 PMC5116244 J, Logan BR, Lee SJ, Jacobsen PB, Wood WA, Jim HS, Wingard (Available JR, Horowitz MM, Abidi MH, Fei M, Rawls L, Rizzo JD. Patient- December 1, 2017) reported outcomes and socioeconomic status as predictors of 67 clinical outcomes after hematopoietic stem cell transplantation: A study from the Blood and Marrow Transplant Clinical Trials Network 0902 trial. Biology of Blood and Marrow Transplantation. 2016 Dec 1; 22(12):2256-2263. Epub 2016 Aug 23.

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Protocol Number Publication PMCID Number Shenoy S, Eapen M, Panepinto JA, Logan BR, Wu J, Abraham BMT CTN 0601 PMC5123194 A, Brochstein J, Chaudhury S, Godder K, Haight AE, Kasow KA, PRIMARY (Available Leung K, Andreansky M, Bhatia M, Dalal J, Haines H, Jaroscak MANUSCRIPT November 24, J, Lazarus H, Levine JE, Krishnamurti L, Margolis D, Megason 2017) 68 GC, Yu LC, Pulsipher MA, Gersten I, DiFronzo N, Horowitz M, Walters MC, Kamani N. A BMT CTN Phase II trial of unrelated donor marrow transplantation for children with severe sickle cell disease. Blood. 2016 Nov 24; 128(21):2561-2567. Epub 2016 Sept 13. Wingard J, Wood WA, Martens M, Le-Rademacher J, Logan B, BMT CTN 0902 PMC5182134 Knight J, Jacobsen PB, Jim H, Majhail NS, Syrjala K, Rizzo JD, (Available Lee S. Pretransplantation exercise and hematopoietic cell January 1, 2018) 69 transplantation survival: A secondary analysis of Blood and Marrow Transplant Clinical Trials Network (BMT CTN 0902). Biology of Blood and Marrow Transplantation. 2017 Jan 1; 23(1):161-164. Epub 2016 Oct 11. Abu Zaid M, Wu J, Wu C, Logan BR, Yu J, Cutler C, Antin JH, BMT CTN 0402 PMID 27827824 Paczesny S, Choi SW. Plasma biomarkers of risk for death in a (PubMed – In 70 multicenter Phase 3 trial with uniform transplant Process) characteristics post-allogeneic HCT. Blood. 2017 Jan 12; 129(2):162-170. Epub 2016 Nov 8. Syrjala KL, Sutton SK, Yi JC, Jim HSL, Knight JM, Wood WA, BMT CTN 0902 PMC5384862 Jacobsen PB, Majhail NS, Abidi MH, Wingard JR, Horowitz (Available MM, Rizzo JD, Le-Rademacher J, Wu J, Lee SJ. Cancer and April 15, 2018) 71 treatment distress psychometric evaluation over time: A BMT CTN 0902 secondary analysis. Cancer. 2017 Apr 15; 123(8):1416-1423. Epub 2016 Nov 28. Ravandi F, Othus M, O'Brien S, Forman SJ, Ha CS, Wong JYC, SWOG S0805 / PMID – Tallman MS, Paietta E, Racevskis J, Uy GL, Horowitz M, Takebe BMT CTN 0805 In Process N, Little R, Borate U, Kebriaei P, Kingsbury L, Kantarjian H, PRIMARY 72 Radich JP, Erba HP, Appelbaum FR. US intergroup study of MANUSCRIPT chemotherapy plus dasatinib and allogeneic stem cell transplant in Philadelphia chromosome positive ALL. Blood Advances. 2016 Dec 27; 1(3):250-259. Epub 2016 Dec 27. Scott BL, Pasquini MC, Logan BR, Wu J, Devine SM, Porter DL, BMT CTN 0901 PMID 28380315 Maziarz RT, Warlick E, Fernandez HF, Alyea E, Hamadani M, PRIMARY (PubMed – In Bashey A, Giralt S, Geller NL, Leifer E, Le-Rademacher J, MANUSCRIPT Process) Mendizabal A, Horowitz MM, Deeg HJ, Horwitz ME. 73 Myeloablative versus reduced-intensity hematopoietic cell transplantation for acute myeloid leukemia and myelodysplastic syndromes. Journal of Clinical Oncology. 2017 Apr 10; 35(11):1154-1161. Epub 2017 Feb 13.

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Attachment B2: Presentations by Year

Protocol Number Presentation Number

2007

1 Pasquini M, Ewell M, Stadtmauer E, Bredeson C, Alyea E, Stockerl-Goldstein K, Krishnan A, BMT CTN 0102 Sahebi F, Rowley S, Maloney D, Vesole D, Horowitz M, Carter S, Geller N, Giralt S. Biologic assignment clinical trials in hematopoietic stem cell transplantation (HSCT) for multiple myeloma: baseline characteristics by treatment allocation from BMT CTN 0102 according to availability of an HLA-matched sibling donor. Poster presentation: 49th ASH Annual Meeting, Atlanta, GA, December 2007 2 Wingard J, Carter S, Walsh T, Kurtzberg J, Small T, Gersten I, Mendizabal A, Leather H, BMT CTN 0101 Confer D, Baden L, Maziarz R, Stadtmauer E, Bolaños-Meade J, Brown J, DiPersio J, Boeckh M, Marr K. Results of a randomized, double-blind trial of fluconazole (FLU) vs. voriconazole (VORI) for the prevention of invasive fungal infections (IFI) in 600 allogeneic blood and marrow transplant (BMT) patients. Oral presentation: 49th ASH Annual Meeting, Atlanta, GA, December 2007

2008

3 Laport G, Bredeson C, Tomblyn MR, Kahl BS, Goodman SA, Ewell M, Klein J, Horowitz MM, BMT CTN 0202 Vose JM, Negrin RS. Autologous versus reduced-intensity allogeneic hematopoietic cell transplantation for patients with follicular non-Hodgkin lymphoma (FL) beyond first complete response or first partial response. Oral presentation: ASCO Annual Meeting, Chicago, IL, May-June, 2008 4 Alousi A, Weisdorf D, Logan B, Bolaños-Meade J, Goldstein S, Ho V, Hayes-Lattin B, BMT CTN 0302 Wingard J, Horowitz M, Levine J. BMT CTN 0302: A Phase II randomized trial evaluating etanercept, mycophenolate mofetil (MMF), denileukin diftitox, and pentostatin in combination with corticosteroids in 180 patients (pts) with newly diagnosed acute graft vs. host disease (aGVHD). Oral presentation: 50th ASH Annual Meeting, San Francisco, CA, December 2008

2009

5 Devine S, Soiffer R, Pasquini M, Carter S, Hari P, Devore S, Stein A, Lazarus H, Linker C, BMT CTN 0303 Stadtmauer E, Keever-Taylor C, O’Reilly R. HLA-identical sibling-matched, CD34+ selected, T cell depleted peripheral blood stem cells following myeloablative conditioning for first or second remission acute myeloid leukemia (AML): Results of Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Protocol 0303. Oral presentation: 51st ASH Annual Meeting, New Orleans, LA, December 2009

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Protocol Number Presentation Number

2010

6 Pasquini M, Devine S, Mendizabal A, Baden L, Wingard J, Lazarus H, Appelbaum F, Keever- BMT CTN 0303 Taylor C, O'Reilly R, Soiffer R. Comparative effectiveness analysis of CD34+ selected, T cell depleted (TCD) HLA-matched sibling grafts on allogeneic hematopoietic cell transplantation for patients with acute myeloid leukemia (AML) in complete remission. Poster presentation: BMT Tandem Meetings, Orlando, FL, February 2010 7 Gurgol C, Foley A, Belt P, Denzen E, Duffy S, Gallagher C, Grodman C, Horowitz M, Confer Network D, Carter S, on behalf of the BMT CTN Sponsored by NHLBI and NCI. Developing materials abstract for transplant centers to share BMT CTN clinical trial results with their patients, a pilot study. Poster presentation: NCI ASCO Cancer Trials Accrual Symposium, Bethesda, MD, April 2010 8 Foley A, Horowitz M, Confer D, Carter S on behalf of the BMT CTN, sponsored by NHLBI Network and NCI. Development of an accrual assessment tool for BMT CTN transplant trials, a abstract proactive approach. Poster presentation: NCI ASCO Cancer Trials Accrual Symposium, Bethesda, MD, April 2010 9 Pasquini M, Foley A, Carter S, Confer D, Horowitz M, Gurgol C, Giralt S, Schilsky R, BMT CTN 0704 / McCarthy P on behalf of the Cancer and Leukemia Group B and the Blood and Marrow CALGB 100104 / Transplant Clinical Trial Network. Maximizing accrual to transplant trials in multiple ECOG 100104 myeloma (MM), lessons from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN), Eastern Cooperative Oncology Group (ECOG), and Cancer and Leukemia Group B (CALGB) collaboration. Poster presentation: NCI ASCO Cancer Trials Accrual Symposium, Bethesda, MD, April 2010 10 Keever-Taylor C, Devine SM, Soiffer RJ, Carter SL, Pasquini MC, Hari P, Stein A, Lazarus HM, BMT CTN 0303 Linker C, Goldstein S, O’Reilly RJ on behalf of the BMT CTN. Characteristics of CD34- enriched products processed at multiple centers using the CliniMacs System - BMT CTN 0303. Oral presentation: International Society for Cellular Therapy 16th Annual Meeting, Philadelphia, PA, May 2010 11 McCarthy PL, Owzar K, Anderson KC, Hofmeister CC, Hassoun H, Hurd DD, Stadtmauer EA, BMT CTN 0704 / Giralt S, Hars V, Linker CA. Phase III intergroup study of lenalidomide versus placebo CALGB 100104 / maintenance therapy following single autologous stem cell transplant (ASCT) for multiple ECOG 100104 myeloma (MM): CALGB 100104. Oral presentation: ASCO Annual Meeting, Chicago, IL, June 2010

190

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 Attachment B2: Presentations

Protocol Number Presentation Number 12 McCarthy PL, Owzar K, Anderson K, Hofmeister CC, Hurd DD, Hassoun H, Giralt S, BMT CTN 0704 / Stadtmauer EA, Richardson PG, Weisdorf DJ, Vij R, Moreb JS, Callander N, Van Besien K, CALGB 100104 / Gentile T, Isola L, Maziarz RT, Gabriel DA, Bashey A, Landau H, Martin T, Qazilbash MH, ECOG 100104 Levitan D, McClune B, Hars V, Postiglione J, Jiang C, Bennett E, Barry SS, Bressler L, Kelly M, Sexton M, Rosenbaum C, Hari P, Pasquini MC, Horowitz MM, Shea TC, Devine SM, Linker C. Phase III intergroup study of lenalidomide versus placebo maintenance therapy following single autologous hematopoietic stem cell transplantation (AHSCT) for multiple myeloma: CALGB 100104. Oral presentation: 52nd ASH Annual Meeting, Orlando, FL, December 2010 13 Krishnan A, Pasquini MC, Ewell M, Stadtmauer EA, Alyea EP, Antin JH, Comenzo RL, BMT CTN 0102 Goodman S, Hari P, Negrin R, Qazilbash MH, Rowley SD, Sahebi F, Somlo G, Vesole DH, Vogl DT, Weisdorf DJ, Geller N, Horowitz MM, Giralt S, Maloney DG. Tandem autologous hematopoietic stem cell transplants (AuHCT) with or without maintenance therapy (auto- auto) versus single AuHCT followed by HLA matched sibling non-myeloablative allogeneic HCT (auto-allo) for patients with standard risk (SR) multiple myeloma (MM): Results from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0102 trial. Oral presentation: 52nd ASH Annual Meeting, Orlando, FL, December 2010 14 Stadtmauer EA, Krishnan A, Pasquini MC, Ewell M, Alyea EP, Antin JH, Castro-Malaspina H, BMT CTN 0102 Kassim AA, Negrin R, Qazilbash MH, Rizzo JD, Rowley SD, Sahebi F, Somlo G, Vesole DH, Vogl DT, Weisdorf DJ, Geller N, Horowitz MM, Maloney DG, Giralt S. Tandem autologous stem cell transplants (auto-auto) with or without maintenance therapy versus single autologous transplant followed by HLA-matched sibling non-myeloablative allogeneic stem cell transplant (auto-allo) for patients (pts) with high risk (HR) multiple myeloma: Results from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0102 Trial. Oral presentation: 52nd ASH Annual Meeting, Orlando, FL, December 2010 15 Switzer GE, Harrington D, Haagenson MD, Drexler R, Foley A, Confer DL, Bishop M, BMT CTN 0201 Anderlini P, Rowley SD, Leitman S, Anasetti C, Wingard JR. Health-related quality-of-life among adult unrelated stem cell donors: A Blood and Marrow Transplant Clinical Trials Network (BMT CTN) randomized trial of marrow versus PBSC donation. Oral presentation: 52nd ASH Annual Meeting, Orlando, FL, December 2010

2011

16 Fuchs EJ, Wu J, Carter S, Brunstein C, Costa L, Wingard J, Jagasia M, D’Elia J, Eapen M, BMT CTN 0603 O’Donnell PV. Phase II trial of non-myeloablative conditioning and partially HLA- mismatched (HLA-haploidentical) bone marrow transplantation (BMT) for patients with hematologic malignancies: Results of Blood and Marrow Transplant Clinical Trials Network (BMT CTN) protocol 0603. Oral presentation: BMT Tandem Meetings, Honolulu, HI, February 2011 *Received a Best Abstract Award

191

Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 Attachment B2: Presentations

Protocol Number Presentation Number 17 Brunstein CG, Carter S, Fuchs EJ, Karanes C, Devine S, Cutler C, Ballen KK, Thompson J, BMT CTN 0604 O'Donnell PV, Eapen M. Phase II trial of non-myeloablative conditioning (NST) double umbilical cord blood transplantation (DUCBT) from unrelated donors in patients with hematologic malignancies: Results of Blood and Marrow Transplant Clinical Trials Network (BMT CTN) protocol 0604. Oral presentation: BMT Tandem Meetings, Honolulu, HI, February 2011 *Received a Best Abstract Award 18 Levine JE, Logan BR, Wu J, Alousi AM, Bolaños-Meade J, Ho VT, Weisdorf DJ, Paczesny S. BMT CTN 0302 GVHD biomarkers measured during treatment independently predict response to therapy and survival: A Blood and Marrow Transplant Clinical Trials Network study. Oral presentation: 37th EBMT Annual Meeting, Paris, France, April 2011 19 McCarthy P, Owzar K, Anderson K, Hofmeister C, Richardson P, Hassoun H, Stadtmauer E, BMT CTN 0704 / Giralt S, Hurd D, Hars V, Jiang C, Postiglione J, Bressler L, Devine S, Linker C. Phase III CALGB 100104 / intergroup study of lenalidomide versus placebo maintenance therapy following single ECOG 100104 autologous stem cell transplant (ASCT) for multiple myeloma (MM): CALGB ECOG BMT CTN 100104. Oral presentation: 13th International Myeloma Workshop, Paris, France, May 2011 20 Krishnan A, Pasquini M, Logan B, Stadtmauer EA, Alyea III E, Antin J, Comenzo R, Goodman BMT CTN 0102 S, Hari P, Negrin R, Qazilbash M, Rowley S, Sahebi F, Somlo G, Vesole D, Vogl D, Weisdorf D, Wu J, Geller N, Horowitz MM, Giralt S, Maloney D. Tandem autologous HCT (auto-auto) versus single autologous HCT followed by HLA matched sibling non-myeloablative allogeneic HCT (auto-allo) for patients with standard risk multiple myeloma: Results from the BMT-CTN 0102 trial. Poster presentation: 13th International Myeloma Workshop, Paris, France, May 2011

21 Hari P, Pasquini M, Logan B, Stadtmauer E, Krishnan A, Howard A, Alvi S, Harding S, Carter BMT CTN 0102 S, Rajkumar V, Alyea III E, Qazilbash M, Laport G, Maloney D, Giralt S, Vesole D. Immunoglobulin free light chain (FLC) and heavy chain/light chain (HLC) assays – comparison with electrophoretic responses in multiple myeloma (MM). Poster presentation: 53rd ASH Annual Meeting, San Diego, CA, December 2011

22 Anasetti C, Logan B, Lee SJ, Waller EK, Weisdorf D, Wingard JR, Cutler C, Westervelt P, BMT CTN 0201 Woolfrey A, Couban S, Johnston L, Maziarz R, Pulsipher M, Anderlini P, Bensinger W, Leitman S, Rowley SD, Carter SL, Horowitz MM, Confer DL. Increased incidence of chronic graft-versus-host disease (GVHD) and no survival advantage with filgrastim-mobilized peripheral blood stem cells (PBSC) compared to bone marrow (BM) transplants from unrelated donors: Results of Blood and Marrow Transplant Clinical Trials Network (BMT CTN) protocol 0201, a Phase III, prospective, randomized trial. Oral presentation (plenary session): 53rd ASH Annual Meeting, San Diego, CA, December 2011

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Protocol Number Presentation Number 23 Waller EK, Harris WAC, Devine S, Porter DL, Mineishi S, McCarty JM, Gonzalez CE, Spitzer BMT CTN 0201 TR, Krijanovski OI, Linenberger ML, Woolfrey A, Howard A, Gurgol C, Logan BR, Confer DL, Anasetti C. Larger numbers of donor naïve CD8+ T-cells and plasmacytoid dendritic cell precursors in allogeneic BM grafts from unrelated donors are associated with improved survival: Results from BMT CTN 0201. Oral presentation: 53rd ASH Annual Meeting, San Diego, CA, December 2011 24 Tolar J, Deeg HJ, Arai S, Horwitz M, Antin JH, McCarty J, Adams R, Eapen M, Ewell M, Leifer BMT CTN 0301 E, Gersten I, Carter SL, Horowitz MM, Confer D, Nakamura R, Pulsipher MA, DiFronzo N, Anderlini P. Fludarabine-based conditioning for allogeneic marrow transplantation from unrelated donors in severe aplastic anemia (SAA): Serious and unexpected adverse events in pre-defined cyclophosphamide (CY) dose levels. Poster presentation: 53rd ASH Annual Meeting, San Diego, CA, December 2011 25 Vose JM, Carter SL, Burns L, Ayala E, Press O, Moskowitz C, Stadtmauer E, Mineishi S, BMT CTN 0401 Ambinder R, Fenske T, Horowitz M, Tomblyn M. Randomized Phase III trial of 131Iodine- Tositumomab (Bexxar)/Carmustine, Etoposide, Cytarabine, Melphalan (BEAM) versus Rituximab/BEAM and autologous stem cell transplantation for relapsed diffuse large B-cell lymphoma (DLBCL): No difference in progression-free (PFS) or overall survival (OS). Oral presentation: 53rd ASH Annual Meeting, San Diego, CA, December 2011 26 Spellecy R, Denzen E, Burton Santibáñez M, Moore H, Foley A, Gersten I, Gurgol C, Network Horowitz M, Majhail N, Murphy E. Informed consent: Improving the form and the process. abstract Oral presentation: Public Responsibility in Medicine and Research (PRIM&R) Advancing Ethical Research Conference, National Harbor, MD, December 2011

2012

27 Waller EK, Harris WA, Devine S, Porter DL, Ferrara J, McCarty JM, Gonzalez CE, Spitzer TR, BMT CTN 0201 Krijanovski OI, Howard A, Gurgol C, Logan BR, Confer DL, Anasetti C. Grade III-IV acute GVHD and treatment-related mortality are reduced among recipients of larger numbers of donor naïve CD8+ T-cells and plasmacytoid dendritic cell precursors in allogeneic BM grafts from unrelated donors: Results from BMT CTN 0201. Oral presentation: 38th EBMT Annual Meeting, Geneva, Switzerland, April 2012 28 Anderlini P, Tolar J, Deeg HJ, Arai S, Horwitz M, Antin JH, McCarty JM, Adams RH, Ewell M, BMT CTN 0301 Leifer E, Gersten I, Carter SL, Horowitz MM, Confer DL, Nakamura R, Pulsipher M, DiFronzo NL, Eapen M. Fludarabine-based conditioning for allogeneic marrow transplantation from unrelated donors in severe aplastic anaemia: Serious and unexpected adverse events in pre-defined cyclophosphamide dose levels. Poster presentation: 38th EBMT Annual Meeting, Geneva, Switzerland, April 2012 29 Crann ME, Mendizabal AM, Gersten ID, Carter SL. Adverse event reporting for Network hematopoietic stem cell transplant studies. abstract Poster presentation: Society for Clinical Trials 33rd Annual Meeting, Miami, FL, May 2012

193

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Protocol Number Presentation Number 30 Anasetti C, Logan B, Lee SJ, Waller EK, Weisdorf D, Wingard JR, Cutler C, Westervelt P, BMT CTN 0201 Woolfrey A, Couban S, Johnston L, Maziarz R, Pulsipher M, Anderlini P, Bensinger W, Leitman S, Rowley SD, Carter SL, Horowitz MM, Confer DL. Increased incidence of chronic graft-versus-host disease (GVHD) and no survival advantage with filgrastim-mobilized peripheral blood stem cells (PBSC) compared to bone marrow transplants from unrelated donors: results of Blood and Marrow Transplant Clinical Trials Network (BMT CTN) protocol #0201, a Phase III, prospective, randomized trial. Oral presentation: ASCO Annual Meeting (ASCO/ASH Joint Session), Chicago, IL, June 2012 31 Cutler C, Logan BR, Nakamura R, Johnston L, Choi SW, Porter DL, Hogan WJ, Pasquini MC, BMT CTN 0402 MacMillan ML, Wingard JR, Waller EK, Grupp SA, McCarthy PL, Wu J, Hu Z, Carter SL, Horowitz MM, Antin JH. Tacrolimus/sirolimus vs. tacrolimus/methotrexate for graft-vs.- host disease prophylaxis after HLA-matched, related donor hematopoietic stem cell transplantation: Results of Bone Marrow Transplant Clinical Trials Network 0402. Oral presentation: 54th ASH Annual Meeting, Atlanta, GA, December 2012 32 Wagner JE, Eapen M, Carter SL, Haut P, Peres E, Schultz K, Thompson J, Wall D, Kurtzberg BMT CTN 0501 J. No survival advantage after double umbilical cord blood (UCB) compared to single UCB transplant in children with hematological malignancy: Results of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN 0501) randomized trial. Oral presentation: 54th ASH Annual Meeting, Atlanta, GA, December 2012 33 Devine SM, Owzar K, Blum W, DeAngelo DJ, Stone RM, Hsu JW, Champlin R, Chen YA, Vij BMT CTN 0502 / R, Slack JL, Soiffer RJ, Larson RA, Shea TC, Hars V, Bennett E, Spangle S, Giralt SA, Carter SL, CALGB 100103 Horowitz MM, Linker C, Alyea III EP. A Phase II study of allogeneic transplantation for older patients with AML in first complete remission using a reduced intensity conditioning regimen: Results from CALGB 100103/BMT CTN 0502. Oral presentation: 54th ASH Annual Meeting, Atlanta, GA, December 2012

2013

34 Yanik G, Ho VT, Horowitz MM, Weisdorf DJ, Logan BR, Wu J, Soiffer RJ, Wingard JR, Levine BMT CTN 0403 JE, Ferrara JL, Giralt SA, White E, Carter SL, DiFronzo N, Cooke KR. Randomized, double blind, placebo-controlled trial of a TNF inhibitor (etanercept) for the treatment of idiopathic pneumonia syndrome (IPS) after allogeneic stem cell transplant (SCT), a Blood and Marrow Transplant Clinical Trials Network (BMT CTN) study. Oral presentation: BMT Tandem Meetings, Salt Lake City, UT, February 2013 35 Kurtzberg J, Carter SL, Mendizabal A, Wall DA, Schultz KR, Kernan NA, Eapen M, Wagner BMT CTN 0501 JE. Superior survival after single unit umbilical cord blood transplantation (UCBT) in children with hematological malignancies treated on Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0501 relative to the cord blood transplantation (COBLT). Oral presentation: BMT Tandem Meetings, Salt Lake City, UT, February 2013

194

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Protocol Number Presentation Number 36 Bolaños-Meade J, Logan BR, Alousi AM, Antin JH, Barowski K, Carter SL, Hexner EO, BMT CTN 0802 Horowitz MM, Levine JE, MacMillan ML, Martin PJ, Nakamura R, Pasquini MC, Weisdorf DJ, Westervelt P, Ho VT. A multi-center, randomized, double blind, Phase III clinical trial comparing steroids/placebo vs. steroids/mycophenolate mofetil as initial therapy for acute graft-versus-host disease. Blood and Marrow Transplant Clinical Trials Network Study 0802. Oral presentation: BMT Tandem Meetings, Salt Lake City, UT, February 2013 37 McCarthy P, Owzar K, Hofmeister C, Richardson P, Hassoun H, Stadtmauer E, Giralt S, BMT CTN 0704 / Hurd D, Qazilbash M, McClune B, Pasquini M, Hars V, Jiang C, Postiglione J, Kelly M, CALGB 100104 / Bressler L, Devine S, Anderson K, Linker C. Analysis of overall survival (OS) in the context of ECOG 100104 cross-over from placebo to lenalidomide and the incidence of second primary malignancies (SPM) in the Phase III study of lenalidomide versus placebo maintenance therapy following autologous stem cell transplant (ASCT) for multiple myeloma (MM), CALGB (Alliance) ECOG, BMT CTN 100104. Oral presentation: 14th International Myeloma Workshop, Kyoto, Japan, April 2013 38 Lee SJ, Le-Rademacher JL, Jim H, Syrjala KL, Wingard JL, Logan BR, Wu J, Majhail NS, Wood BMT CTN 0902 WA, Rizzo JD, Geller NL, Kitko CL, Faber Jr. EA, Abidi MH, Slater SE, Horowitz MM, Jacobsen P. Exercise and stress management training for patients undergoing autologous or allogeneic hematopoietic cell transplantation. Results from Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0902. Oral presentation: 55th ASH Annual Meeting, New Orleans, LA, December 2013

2014

39 Levine JE, Braun TM, Harris AC, Holler E, Taylor A, Miller H, Magenau J, Weisdorf DJ, Ho BMT CTN 0302 VT, Bolaños-Meade J, Alousi AM, Ferrara JL. A new Ann Arbor grading system uses and 0802 biomarkers to risk stratify patients for non relapse mortality at the onset of acute graft versus host disease. Oral presentation: 40th EBMT Annual Meeting, Milan, Italy, March-April 2014 40 Mendizabal AM, Pasquini MC, Logan BR, Gersten ID, DiFronzo NL, Wagner EL, Merritt WD, Network Wu RS, Confer DL, Horowitz MM. Leveraging resources to design, conduct, and analyze abstract hematopoietic stem cell transplant clinical trials: The ongoing collaboration between the Center for International Blood and Marrow Transplant Research and the Blood and Marrow Transplant Clinical Trials Network. Oral presentation: Society for Clinical Trials 35th Annual Meeting, Philadelphia, PA, May 2014 41 Hope WW, Walsh TJ, Goodwin J, Peloquin C, Howard A, Kurtzberg J, Mendizabal A, Confer BMT CTN 0101 D, Bulitta J, Neely M, Baden L, Wingard J. Relationship between voriconazole concentrations and the probability of breakthrough fungal infections. Poster presentation: 54th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, DC, September 2014

195

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Protocol Number Presentation Number 42 Anderlini P, Wu J, Deeg J, Gersten I, Ewell M, Tolar J, Antin JH, Arai S, Horwitz ME, McCarty BMT CTN 0301 JM, Nakamura R, Pulsipher MA, Adams RH, Leifer E, Carter SL, DiFronzo NL, Horowitz MM, Confer DL, Eapen M. Optimized cyclophosphamide (CY) dosing in combination with fludarabine, TBI and ATG as conditioning for unrelated donor bone marrow transplantation (BMT) in severe aplastic anemia (SAA): A Phase I/II study from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN). Oral presentation: 56th ASH Annual Meeting, San Francisco, CA, December 2014 43 Holtan SG, Verneris MR, Schultz KR, Newell L, Meyers G, He FC, DeFor TE, MacMillan ML, BMT CTN 0302 Cooley SA, Panoskaltsis-Mortari A, Weisdorf DJ. Circulating angiogenic factors as and 0802 biomarkers of acute GVHD onset and response to therapy: Repair and regeneration versus endothelial damage and inflammation. Poster presentation: 56th ASH Annual Meeting, San Francisco, CA, December 2014 44 Levine JE, Braun TM, Harris AC, Holler E, Taylor A, Miller HK, Magenau JM, Weisdorf DJ, Ho BMT CTN 0302 VT, Bolaños-Meade J, Alousi AM, Ferrara JL. A biomarker algorithm defines onset grades of and 0802 acute graft-vs-host disease with distinct non-relapse mortality. Oral presentation: 56th ASH Annual Meeting, San Francisco, CA, December 2014 45 Laport GG, Wu J, Logan BR, Bachanova V, Hosing CM, Fenske TS, Longo WL, Devine SM, BMT CTN 0701 Nademanee AP, Gersten I, Horowitz MM, Lazarus HM, Riches ML. Reduced intensity conditioning (RIC) with rituximab yields excellent outcomes after allogeneic hematopoietic cell transplantation (alloHCT) for relapsed follicular lymphoma (FL): A Phase II multicenter trial from the Blood and Marrow Transplant Network (BMT CTN 0701). Oral presentation: 56th ASH Annual Meeting, San Francisco, CA, December 2014 46 Smith EP, Li H, Friedberg JW, Constine L, Rimsza LM, Laport GG, Popplewell LL, Maloney BMT CTN 0703 DG, Leblanc M, Forman SJ, Fisher RI, Stiff PJ. SWOG S0410 / BMT CTN 0703: A Phase II trial of tandem autologous stem cell transplantation (AHCT) for patients with primary progressive or recurrent Hodgkin lymphoma (HL). Oral presentation: 56th ASH Annual Meeting, San Francisco, CA, December 2014 47 Alvarnas J, Le-Rademacher J, Wang Y, Little RF, Akpek G, Ayala E, Devine S, Kaplan L, Noy BMT CTN 0803 A, Popat U, Thompson J, Horowitz MM, Mendizabal A, Navarro WH, Ambinder R. Autologous hematopoietic stem cell transplantation (AHCT) in patients with chemotherapy-sensitive, relapsed / refractory (CSRR) human immunodeficiency virus (HIV)-associated lymphoma (HAL): Results from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN 0803) / AIDS Malignancy Consortium (AMC-071) trial. Oral presentation: 56th ASH Annual Meeting, San Francisco, CA, December 2014 48 Wood WA, Le-Rademacher J, Fei M, Logan BR, Syrjala KL, Majhail NS, Wingard JR, Abidi BMT CTN 0902

MH, Geller NL, Wu J, Rizzo JD, Faber Jr EA., Jim H, Jacobsen P, Horowitz MM, Lee SJ. Patient-reported quality of life is an independent predictor of survival after allogeneic hematopoietic cell transplantation: A secondary analysis from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0902. Oral presentation: 56th ASH Annual Meeting, San Francisco, CA, December 2014

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Protocol Number Presentation Number

2015

49 Holtan S, Verneris MR, Schultz KR, Newell LF, Meyers G, He F, DeFor TE, MacMillan ML, BMT CTN 0302 Cooley S, Blazar BR, Panoskaltsis-Mortari A, Weisdorf DJ. Prognostic impact of follistatin in and 0802 acute graft-versus-host disease: Results from BMT CTN 0302 and 0802. Oral presentation: BMT Tandem Meetings, San Diego, CA, February 2015 50 Young JH, Logan BR, Wu J, Wingard JR, Weisdorf DJ, Mudrick C, Knust K, Horowitz MM, BMT CTN 0201 Confer DL, Anasetti C. More infections with transplantation of bone marrow, versus peripheral-blood stem cells, from unrelated donors. Oral presentation: BMT Tandem Meetings, San Diego, CA, February 2015 51 Moore HK, Denzen EM, Idossa L, Murphy EA, Foley A, Gersten ID, Majhail NS, Spellecy R, BMT CTN 1205 Horowitz MM. Easy-to-read informed consent (ETRIC) forms for multi-center hematopoietic cell transplant clinical trials (BMT CTN 1205). Poster presentation: Institute for Healthcare Advancement’s 14th Annual Health Literacy Conference, Irvine, CA, May 2015 52 Holstein SA, Owzar K, Richardson PG, Jiang C, Hofmeister CC, Hassoun H, Hurd DD, BMT CTN 0704 / Stadtmauer EA, Giralt S, Devine SM, Hars V, Postiglione JR, Weisdorf DJ, Vij R, Moreb JS, CALGB 100104 / Callander NS, Martin TG, Shea TC, Anderson KC, McCarthy PL. Updated analysis of CALGB / ECOG 100104 ECOG / BMT CTN 100104: Lenalidomide (Len) vs. placebo (PBO) maintenance therapy after single autologous stem cell transplant (ASCT) for multiple myeloma (MM). Poster presentation: ASCO Annual Meeting, Chicago, IL, May-June 2015 53 D'Souza A, Pasquini MC, Logan BR, Giralt SA, Krishnan A, Antin J, Howard A, Horowitz MM, BMT CTN 0102 Goodman S, Laport GG, Qazilbash M, Mendizabal AM, Sahebi F, Weisdorf D, Vesole D, Stadtmauer EA, Maloney D, Hari P. Heavy light chain ratio normalization allows identification of electrophoretic non-complete response patients with improved outcomes: A long term follow up update for BMT CTN 0102 correlative study. Poster presentation: 20th Congress of European Hematology Association, Vienna, Austria, June 2015 54 Knight JM, Martens M, Syrjala KL, Le-Rademacher J, Logan BR, Lee SJ, Jacobsen PB, Wood BMT CTN 0902 WA, Jim H, Wingard JR, Horowitz MM, Majhail NS, Abidi MH, Geller NL, Fei M, Wu J, Rizzo JD. Pre-transplant health-related quality of life factors as predictors of outcomes following hematopoietic cell transplantation: A study from the BMT CTN 0902 trial. Oral presentation: IPOS / APOS World Congress on Psycho-Oncology, Washington DC, July-August 2015 55 Syrjala KL, Sutton SK, Yi JC, Jim H, Knight JM, Wood WA, Jacobsen PB, Majhail NS, Abidi BMT CTN 0902 MH, Wingard JR, Horowitz MM, Rizzo JD, Le-Rademacher J, Wu J, Lee SJ. Cancer and treatment distress measurement over time in a multicenter cohort of hematopoietic cell transplantation (HCT) recipients (BMT CTN 0902). Oral presentation: IPOS / APOS World Congress on Psycho-Oncology, Washington DC, July-August 2015

197

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Protocol Number Presentation Number 56 Holstein SA, Owzar K, Richardson PG, Jiang C, Hofmeister CC, Hassoun H, Hurd DD, BMT CTN 0704 / Stadtmauer EA, Giralt S, Devine SM, Hars V, Postiglione JR, Weisdorf DJ, Vij R, Moreb JS, CALGB 100104 / Callander NS, Pasquini MC, Martin TG, Shea TC, Anderson KC, McCarthy PL. Analysis of ECOG 100104 second primary malignancies (SPMs) in CALGB (Alliance) / ECOG / BMT CTN 100104. Poster presentation: 15th International Myeloma Workshop, Rome, Italy, September 2015

57 Scott BL, Pasquini MC, Logan BR, Wu J, Devine S, Porter DL, Maziarz RT, Warlick E, BMT CTN 0901 Fernandez HF, Alyea EP, Hamadani M, Bashey A, Giralt SA, Leifer E, Geller N, Le- Rademacher J, Mendizabal AM, Horowitz MM, Deeg HJ, Horwitz ME. Results of a Phase III randomized, multi-center study of allogeneic stem cell transplantation after high versus reduced intensity conditioning in patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML): Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0901. Oral presentation: 57th ASH Annual Meeting, Orlando, FL, December 2015 * Late Breaking Abstract 58 Ravandi F, Othus M, O'Brien S, Forman SJ, Ha CS, Wong JY, Tallman MS, Paietta E, BMT CTN 0805 Racevskis J, Uy GL, Borate U, Kebriaei P, Kingsbury L, Kantarjian HM, Radich JP, Erba HP, Appelbaum FR. Multi-center US intergroup study of intensive chemotherapy plus dasatinib followed by allogeneic stem cell transplant in patients with Philadelphia chromosome positive acute lymphoblastic leukemia younger than 60. Oral presentation: 57th ASH Annual Meeting, Orlando, FL, December 2015 59 Shenoy S, Eapen M, Wu J, Walters MC, Levine JE, Logan BR, Gersten ID, Kamani NR. A BMT CTN 0601 multicenter Phase II trial of unrelated donor reduced intensity bone marrow transplantation for children with severe sickle cell disease (SCURT): Results of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN 0601) study. Oral presentation: 57th ASH Annual Meeting, Orlando, FL, December 2015 60 Lee SJ, Logan BR, Westervelt P, Cutler CS, Woolfrey AE, Khan S, Waller EK, Maziarz RT, Wu BMT CTN 0201 J, Shaw BE, Confer DL, Horowitz MM, Anasetti C. 5 year results of BMT CTN 0201: Unrelated donor bone marrow is associated with better psychological well-being and less burdensome chronic GVHD symptoms than peripheral blood. Oral presentation: 57th ASH Annual Meeting, Orlando, FL, December 2015

2016

61 Carpenter PA, Logan BR, Lee SJ, Weisdorf DJ, Johnston L, Costa LJ, Kitko CL, Bolaños- BMT CTN 0801 Meade J, Alousi AM, Horowitz MM, Abhyankar S, Waller EK, Mendizabal A, Wang Y, Lazaryan A, Carter SL, Nemecek ER, Pavletic SZ, Cutler CS, Arora M. Prednisone (PDN) / sirolimus (SRL) compared to PDN / SRL / calcineurin inhibitor (CNI) as treatment for chronic graft-versus-host-disease (cGVHD): A randomized Phase II study from the Blood and Marrow Transplant Clinical Trials Network. Oral presentation: BMT Tandem Meetings, Honolulu, HI, February 2016

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Protocol Number Presentation Number 62 Scott BL, Pasquini MC, Logan BR, Wu J, Devine S, Porter DL, Maziarz RT, Warlick E, BMT CTN 0901 Fernandez HF, Alyea EP, Hamadani M, Bashey A, Giralt SA, Leifer E, Geller N, Le- Rademacher J, Mendizabal AM, Horowitz MM, Deeg HJ, Horwitz ME. Results of a Phase III randomized, multi-center study of allogeneic stem cell transplantation after high versus reduced intensity conditioning in patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML): Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0901. Oral presentation: BMT Tandem Meetings, Honolulu, HI, February 2016 * Special Invited Abstract: BMT CTN 0901 Randomized Trial 63 Newell LF, Verneris MR, Panoskaltsis-Mortari A, Defor TE, Blazar BR, Cutler CS, Antin JH, BMT CTN 0402 MacMillan ML, Weisdorf DJ, Holtan S. Angiogenic factors, inflammation, and outcomes in myeloablative allogeneic hematopoietic cell transplantation: A biomarker analysis of GVHD prophylaxis in Blood and Marrow Transplant Clinical Trials Network protocol (BMT CTN) 0402. Oral presentation: BMT Tandem Meetings, Honolulu, HI, February 2016 64 Shenoy S, Eapen M, Wu J, Walters MC, Levine JE, Logan BR, Gersten ID, Kamani NR. BMT CTN 0601 Results of the Blood and Marrow Transplant Clinical Trials Network study BMT CTN 0601: SCURT - a multicenter Phase II trial of unrelated donor reduced intensity bone marrow transplantation (BMT) for children with severe sickle cell disease. Oral presentation: BMT Tandem Meetings, Honolulu, HI, February 2016 65 Maziarz RT, Lazarus HM, Riches ML, Mudrick C, Mendizabal A. BMT CTN trials: A rich Network source for regimen related toxicity assessments in the modern era. abstract Poster presentation: BMT Tandem Meetings, Honolulu, HI, February 2016 66 Anderlini P, Wu J, Deeg HJ, Gersten ID, Ewell M, Tolar J, Antin J, Arai S, Horwitz M, BMT CTN 0301 McCarty J, Nakamura R, Pulsipher M, Adams R, Leifer E, DiFronzo N, Horowitz MM, Confer DL, Eapen M. Cyclophosphamide (CY) conditioning in patients with severe aplastic anaemia (SAA) given unrelated marrow transplantation: Final results of a Phase 1-2 dose de-escalation study from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN 0301). Poster presentation: 42nd EBMT Annual Meeting, Valencia, Spain, April 2016 67 Burns LJ, Logan BR, Chitphakdithai P, Miller J, Drexler R, Spellman S, Switzer G, Wingard BMT CTN 0201 J, Anasetti C, Confer DL. Faster recovery of unrelated donors of peripheral blood stem cells (PBSC) vs bone marrow (BM): A prespecified analysis from BMT CTN 0201. Poster presentation: 42nd EBMT Annual Meeting, Valencia, Spain, April 2016 68 Attal M, Palumbo A, Holstein SA, Lauwers-Cances V, Petrucci MT, Richardson PG, Hulin BMT CTN 0704 / C, Tosi P, Anderson KC, Caillot D, Magarotto V, Moreau P, Marit G, Yu Z, McCarthy PL. CALGB 100104 / Lenalidomide (LEN) maintenance (MNTC) after high-dose melphalan and autologous ECOG 100104 stem cell transplant (ASCT) in multiple myeloma (MM): A meta-analysis (MA) of overall survival (OS). Oral abstract presentation: ASCO Annual Meeting, Chicago, IL, June 2016

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Protocol Number Presentation Number 69 Knight JM, Martens M, Syrjala KL, Le-Rademacher J, Logan BR, Lee SJ, Jacobsen PB, BMT CTN 0902 Wood WA, Jim H, Wingard JR, Horowitz MM, Majhail NS, Abidi MH, Geller NL, Fei M, Wu J, Rizzo JD. Psychosocial and socioeconomic status as predictors of outcomes following hematopoietic stem cell transplantation: An ancillary study from the BMT CTN

0902 randomized controlled trial (RCT). Poster presentation: PsychoNeuroImmunology Research Society’s 23rd Annual Scientific Meeting, Brighton, United Kingdom, June 2016 70 McCarthy PL, Palumbo A, Holstein SA, Lauwers-Cances V, Petrucci MT, Richardson PG, BMT CTN 0704 / Hulin C, Tosi P, Anderson KC, Caillot D, Magarotto V, Moreau P, Marit G, Yu Z, Attal M. A CALGB 100104 / meta-analysis of overall survival in patients with multiple myeloma treated with ECOG 100104 lenalidomide maintenance after high-dose melphalan and autologous stem cell transplant. Oral presentation: 21st Congress of the European Hematology Association, Copenhagen Denmark, June 2016 71 Eapen M, Kurtzberg J, Zhang M, Mendizabal AM, Chang KW, Duval M, Fei M, Neudorf S, BMT CTN 0501 De Oliveira SN, Wall DA, Schultz KR, Horowitz MM, Wagner JE. Umbilical cord blood (UCB) transplantation in children with acute leukemia: Impact of conditioning regimen on transplant outcomes. Oral presentation: 58th ASH Annual Meeting, San Diego, CA, December 2016

72 Newell LF, DeFor TE, Cutler CS, Verneris MR, Blazar BR, Antin JH, Howard A, Wu J, BMT CTN 0402 MacMillan ML, Panoskaltsis-Mortari A, Weisdorf DJ, Holtan SG. Follistatin and endoglin: Potential biomarkers of endothelial damage and non-relapse mortality after myeloablative allogeneic hematopoietic cell transplantation in Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0402. Oral presentation: 58th ASH Annual Meeting, San Diego, CA, December 2016 73 Makowski M, Ahmed E, Schlotter S, Pearson R, Kitzler R, Alvarnas JC, Le-Rademacher J, BMT CTN 0803 Wang Y, Little RF, Akpek G, Ayala E, Devine SM, Kaplan LD, Noy A, Popat UR, Hsu JW, Morris LE, Thompson J, Horowitz MM, Mendizabal AM, Levine AM, Krishnan A, Hade E, Hofmeister CC, Forman SJ, Navarro WH, Ambinder RF, Lozanski G, Baiocchi RA. Evaluation of immune recovery following autologous hematopoietic cell transplantation in HIV-related lymphoma: Results of the BMT CTN 0803/AMC 071 Trial. Poster presentation: 58th ASH Annual Meeting, San Diego, CA, December 2016 74 Stadtmauer EA, Pasquini MC, Blackwell B, Knust K, Bashey A, Devine SM, Efebera YA, BMT CTN 0702 Ganguly S, Gasparetto Cristina, Geller N, Giralt SA, Hari P, Horowitz MM, Koreth J, Landau H, McCarthy PL, McClune B, Nelson C, Qazilbash MH, Shah N, Vesole DH, Vij R, Vogl DT, Somlo G, Krishnan A. Comparison of autologous hematopoietic cell transplant (autoHCT), bortezomib, lenalidomide (Len) and dexamethasone (RVD) consolidation with len maintenance (ACM), tandem autoHCT with len maintenance (TAM) and autoHCT with len maintenance (AM) for up-front treatment of patients with multiple myeloma (MM): Primary results from the randomized Phase III trial of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN 0702 – StaMINA Trial). Oral presentation: 58th ASH Annual Meeting, San Diego, CA, December 2016

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Protocol Number Presentation Number

2017

75 Newell LF, DeFor TE, Cutler CS, Verneris MR, Blazar BR, Antin JH, Howard A, Wu J, BMT CTN 0402 MacMillan ML, Panoskaltsis-Mortari A, Weisdorf DJ, Holtan SG. Follistatin and endoglin: Potential biomarkers of endothelial damage and non-relapse mortality after myeloablative allogeneic hematopoietic cell transplantation in Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0402. Oral presentation: BMT Tandem Meetings, Orlando, FL, February 2017 76 Pidala JA, Martens M, Carreras J, Anasetti C, Cutler CS, Lee SJ, Antin JH, Horowitz MM, BMT CTN 0201 Logan BR. Multi-state modeling identifies determinants of successful immune and 0402 suppression discontinuation: Secondary analysis of BMT CTN 0201 and 0402 trials. Oral presentation: BMT Tandem Meetings, Orlando, FL, February 2017 77 Khera N, Mau L, Denzen EM, Houg K, Lee SJ, Horowitz MM, Burns LJ. Understanding BMT CTN 0201 physicians’ perspectives about translating research into clinical practice: Example of Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0201 results. Oral presentation: BMT Tandem Meetings, Orlando, FL, February 2017 78 Krishnan A, Pasquini M, Blackwell B, Knust K, Bashey A, Devine S, Efebera Y, Ganguly S, BMT CTN 0702 Gasparetti C, Geller N, Giralt S, Hari P, Horowitz M, Koreth J, Landau H, McCarthy P, McClune B, Nelson C, Qazilbash M, Shah N, Vesole D, Vij R, Vogl DT, Somlo G, Stadtmauer E. Post autologous transplant (autoHCT) therapies in high risk MM. Subgroup analysis of phase III BMT CTN 0702-STaMINA: AutoHCT followed by lenalidomide maintenance (Len) (AM) versus auto HCT and len and bortezomib (BZ) and dexamethasone consolidation len maintenance (ACM) vs tandem autoHCT len maintenance. Oral presentation: 16th International Myeloma Workshop, New Delhi, India, March 2017 79 McCarthy P, Holstein S, Petrucci MT, Richardson P, Hulin C, Tosi P, Bringhen S, Musto P, BMT CTN 0704 / Anderson KC, Caillot D, Gay F, Moreau P, Marit G, Jung S, Yu Z, Winograd B, Knight R, CALGB 100104 / Palumbo A, Attal M. Lenalidomide (LEN) maintenance following high-dose melphalan ECOG 100104 and autologous stem cell transplant (ASCT) in patients (Pts) with newly diagnosed multiple myeloma (MM): A meta-analysis of overall survival (OS). Oral presentation: 16th International Myeloma Workshop, New Delhi, India, March 2017 80 McCarthy PL, Holstein SA, Jung S-H, Cooper M, Gibson C, Winograd B, Richardson P. BMT CTN 0704 / Overall survival (OS) and progression-free survival (PFS) adjusted for treatment CALGB 100104 / crossover in the CALGB/ECOG 100104 (Alliance) study of lenalidomide (LEN) versus ECOG 100104 placebo (PBO) maintenance after stem cell transplant (SCT) for patients with newly diagnosed multiple myeloma. Oral presentation: 16th International Myeloma Workshop, New Delhi, India, March 2017

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Protocol Number Presentation Number

Upcoming Presentations

81 Nelson C, O’Brien K, Mendizabal A, Gersten I, Uhl L, Chung D, Shah N, Avigan D, Pasquini BMT CTN 1401 M. Translation of a single-center cellular therapy manufacturing approach to a multicenter, center-specific manufacturing platform: The experience of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Protocol #1401. Poster to be presented: Society for Clinical Trials 38th Annual Meeting, Liverpool, United Kingdom, May 2017 82 Nelson C, O’Brien K, Mendizabal A, Gersten I, Uhl L, Chung D, Shah N, Avigan D, Pasquini BMT CTN 1401 M. Development and management of a multi-center, center-specific cellular therapy manufacturing approach: The experience of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Protocol #1401. Poster to be presented: International Society for Cellular Therapy 25th Annual Meeting, London, United Kingdom, May 2017 83 Somlo G, Pasquini MC, Blackwell B, Knust K, Devine S, Efebera Y, Geller N, Giralt S, Hari P, BMT CTN 0702 Koreth J, Landau H, McCarthy P, McClune B, Qazilbash M, Shah N, Vesole DH, Vij R, Vogl DT, Krishnan A, Stadtmauer E. Response status as predictor of survival after autologous hematopoietic cell transplant (AHCT), without or with consolidation (with bortezomib, lenalidomide (Len) and dexamethasone) and len maintenance (AM vs. ACM) versus tandem AHCT and len maintenance (TAM) for up-front treatment of patients (pts) with multiple myeloma (MM). BMT CTN 0702-STaMINA (NCT01109004) Poster to be presented: ASCO Annual Meeting, Chicago IL, June 2017 84 Ambinder RF, Wu J, Logan B, Durand C, Shields R, Popat UR, Little RF, McMahon D, BMT CTN 0903 Mellors JW, Ayala E, Kaplan LD, Noy A, Howard A, Forman SJ, Mendizabal AM, Horowitz MM, Navarro WH, Alvarnas JC. Allogeneic hematopoietic cell transplant (alloHCT) for hematologic malignancies in human immunodeficiency virus infected (HIV) patients (pts): Blood and Marrow Transplant Clinical Trials Network (BMT CTN 0903)/AIDS malignancy consortium (AMC-080) trial. Oral abstract to be presented: ASCO Annual Meeting, Chicago, IL, June 2017

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 Attachment C1: Center Performance Report Template Attachment C: Center Performance Report Attachment C1: Center Performance Report Template

CENTER PERFORMANCE REPORT Center Name: Date of Evaluation: SCIENTIFIC AND ADMINISTRATIVE ACTIVITY Items # Protocol5 N % Total N1 Protocol Chairs or Co-chairs 4 Protocol Team members  Protocol Team conference call participation2 in 2015 /=% Protocol Endpoint Review Call participation3 in 2015 Steering Committee Chair / Chair-Elect / Past-Chair in  % 2015 Steering Committee meeting / call participation in 2015  % Notes: 1 Total N for all centers and all protocols, which were active in 2015. 2 Percentages for call are calculated based on the protocols that the center is one of the chairs / members. 3 Percentages for call are calculated based on the protocols that the center is one of Endpoint Review Committee. 4 ― means not applicable or not calculated. 5 Only protocols that were active in 2015 are included.

PROTOCOL TEAM CONFERENCE CALL PARTICIPATION IN 2015 Protocol Team Not Attending Endpoint Review Not Attending Overall Call Protocol Calls Team Calls Committee Calls Endpoint Review Calls Participation (%)1 0701 0702 0801 0901 1101 1102 1202 Total Note: 1 Based on the protocol team call participation and endpoint review call participation, weighted by the total number of team calls and endpoint review calls.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 Attachment C1: Center Performance Report Template ACTIVATION AND ENROLLMENT

# Projected # Days to # Days from Protocol # Accrual in # Days to PROTOCOL Accrual in Consent Activation to 1st Activated 2015 Activation 20151 (%2) Preview1 Patient

0301

0601

0701

0702

07LT

0803

0804

0901

0902

0903

1101

1102

1202

1203

1204

1205

1301

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 Attachment C1: Center Performance Report Template

# Projected # Days to # Days from Protocol # Accrual in # Days to PROTOCOL Accrual in Consent Activation to 1st Activated 2015 Activation 20151 (%2) Preview1 Patient

1302

1304

1505

N_Total= N_Total= N_Total= Median_Overall= Median_Overall= Median_Overall= Total/Overall N_Recent= (/=%) Median_Recent= Median_Recent= Median_Recent= [4] [85%] [56] [180] [56] Notes: 1 Date of consent preview is available only for BMT CTN-led protocols after 0702. 2 % is the actual accrual total over projected accrual total (including only protocols “activated”). If projected accrual number was not available, the actual accrual number was used as projected number. 3 N_Recent means N only counts the protocols opened within the preceding 4 years (starting with 1101, highlighted in gray). Median_Recent means median only counts the protocols opened within the preceding 4 years. 4  for row “Protocol activated” means site is not participating the study.  for other rows means not activated yet, not applicable, or information not available. 5 Accrual to protocols 07LT, 1203 CIBMTR Control Cohort, and 1505 receive get 50% accrual credit. Non-Caucasian adult and all pediatric patients enrolled on 1202 since 1/26/15 get double accrual credit. 6 Targets are in “[ ]”.

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 Attachment C1: Center Performance Report Template DATA QUALITY

# Accrual in Data Audit Error # Protocol Deviations in 2016 # Required # Forms > 30 Forms > 30 days PROTOCOL # Total Rate (%) (% of Enrolled Patients) Forms Days Overdue Overdue / Patient

0301

0601

0701

0702

07LT

0801

0803

0903

1101

1102

1202

1203

1204

1205

1301

1302

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 Attachment C1: Center Performance Report Template

# Accrual in Data Audit Error # Protocol Deviations in 2016 # Required # Forms > 30 Forms > 30 days PROTOCOL # Total Rate (%) (% of Enrolled Patients) Forms Days Overdue Overdue / Patient

1401

1501

Total/Overall [2%] (%) [2%] [5] Notes: 1 Protocols that have finished following up patients before Jan 1, 2016, and those for which Emmes does not monitor data quality are not included in this table. 2  for row “# Accrual” means site is not participating in the study or not activated yet.  for row “Data audit error rate” means there were no data audit performed in 2016.  for other rows means not applicable due to no patients. 3 Targets are in “[ ]”.

CIBMTR REPORT FORM COMPLIANCE

# BMT CTN Patients # Patients Registered with CIBMTR (%) # CIBMTR Report Forms Due # CIBMTR Report Forms Received (%)

(%) (%)

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 Attachment C1: Center Performance Report Template LABORATORY COMPLIANCE EVALUATION 2016 Quarterly

Protocol # 2015 Overall 2016 Overall Q1 Q2 Q3 Q4

0601 0702 07LT 0803 0903 1101 1102 1202 1203 1204 1301 1302 1401 Annual Rating Notes: OS – Outstanding (93-100%) AA – Above Average (85-92%) AC – Acceptable (65-84%) MA – Marginally Acceptable (50-64%) IN – Improvement Needed (0-49%) -- indicates not participating or no activity in the time period

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 Attachment C1: Center Performance Report Template PERFORMANCE RATING Score Rating Scientific and Administrative Accrual Activation and Enrollment Data Quality Laboratory Compliance Overall Assessment

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 Attachment C2: Center Performance Report Rating Metric

Attachment C2: Center Performance Report Rating Metric

Holds Steering Committee Chair, Past-Chair or Chair-Elect Administrative Activity max=10 Outstanding (10 points) position OR points Protocol Team Chair + > 70% of team calls participation Acceptable (5.1-9 points) % Call Participation × 10 Needs Improvement (0-5 points) Attends < 33% of Protocol Team calls Accrues > 24 patients and meets ≥ 100% of projected accrual OR Accrual max=60 Outstanding (60 points) Enrolls > 48 patients points Score = (Actual/Projected) x 60 then adjust for maximum Acceptable (40-59 points) For centers enrolling 20 or more patients, can get a maximum score of 60; for centers enrolling < 20 patients, can only get a maximum of 45 points even if meeting or exceeding projections Score < 40 points Needs Improvement (<40 points) For centers enrolling < 18 patients, can only get a maximum of 10 points even if meeting or exceeding projections

Activation and Enrollment max=10 Outstanding (10 points) Meets 4 of 4 metrics points  # protocols activated within preceding 4 years Acceptable (5 points) Meets 2-3 of 4 metrics [4]  # days to consent preview [56]  # days to activation [180] Needs Improvement (0 points) Meets < 2 of 4 metrics  # days activation to 1st patient [56] Data Quality max=10 Outstanding (10 points) Meets 4 of 4 metrics points  Data audit error rate [2%] Acceptable (5 points) Meets 2-3 of 4 metrics  % protocol deviations [2%]  Forms >30 days past due per patient [5] Needs Improvement (0 points) Meets < 2 of 4 metrics  CIBMTR form compliance [90%]

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 Attachment C2: Center Performance Report Rating Metric

Laboratory Compliance max=10 Outstanding (8.1-10 points) OS - Outstanding points  Average compliance percentage for all Acceptable (5.1-8.0 points) AA - Above Average 7.5; AC - Acceptable 5.0 participating protocols Needs Improvement UN - Unacceptable; MA - Marginally Acceptable 2.5  Evaluated by Alan Howard (0-5 points) Outstanding > 90 points Overall Assessment max=100 Acceptable 60 – 90 points points Needs Improvement < 60 points; center required to submit action plan

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 Attachment D: Terms and Abbreviations Attachment D: Terms and Abbreviations

Term/ Definition Abbreviation ABC activated B cell-like (type of diffuse large B cell lymphoma) AIDS acquired immunodeficiency syndrome ALL acute lymphoblastic leukemia AML acute myelogenous leukemia ASBMT American Society of Blood and Marrow Transplantation ASCO American Society of Clinical Oncology ASH American Society of Hematology BCR B cell receptor BEAM carmustine (BCNU), etoposide, cytarabine, and melphalan BMT blood and marrow transplant / transplantation BMT CTN Blood and Marrow Transplant Clinical Trials Network (also “the Network”) BTK Bruton’s tyrosine kinase CALGB Cancer and Leukemia Group B (member Alliance for Clinical Trials in Oncology) CIBMTR Center for International Blood and Marrow Transplant Research CLL chronic lymphocytic leukemia COG Children’s Oncology Group CR complete remission CTCAE common terminology criteria for adverse events CTSU Cancer Trials Support Unit CVAD cyclophosphamide, vincristine, adriamycin and dexamethasone DCC Data and Coordinating Center Delayed versus Early Transplant with Revlimid Maintenance and Antimyeloma Triple Therapy; DETERMINATION BMT CTN Protocol 1304 DFCI Dana-Farber Cancer Institute DLBCL diffuse large B cell lymphoma DNA deoxyribonucleic acid DSMB Data and Safety Monitoring Board EBMT European Group for Blood and Marrow Transplantation ECOG Eastern Cooperative Oncology Group ECP extracorporeal photopheresis ETRIC Easy-To-Read Informed Consent; BMT CTN Protocol 1205 FACT Foundation for the Accreditation of Cellular Therapy FDA Food and Drug Administration G-CSF granulocyte-colony stimulating factor GVHD graft-versus-host disease HCT hematopoietic stem cell transplantation HIV human immunodeficiency virus HLA human leukocyte antigen HLH hemophagocytic lymphohistiocytosis IDE investigational device exemption

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 Attachment D: Terms and Abbreviations

Term/ Definition Abbreviation IFM Intergroupe Francophone du Myelome IND investigational new drug IPS idiopathic pneumonia syndrome IRB Institutional Review Board MDS myelodysplastic syndrome MM multiple myeloma MMF mycophenolate mofetil mRNA messenger ribonucleic acid MRD minimum residual disease NCI National Cancer Institute NCTN National Clinical Trials Network NGS next generation sequencing NHLBI National Heart, Lung, and Blood Institute NIAID National Institute of Allergy and Infectious Diseases NIH National Institutes of Health NK natural killer NMDP National Marrow Donor Program PBMC peripheral blood mononuclear cell PBMTC Pediatric Blood and Marrow Transplant Consortium PBSC peripheral blood stem cell PFS progression-free survival PI Principal Investigator PR partial remission PRC protocol review committee PRES posterior reversible encephalopathy syndrome Prevention and Reduction of GVHD and Relapse Enhancing Survival after Stem Cell PROGRESS Transplantation; BMT CTN Protocol 1203 PROGRESS II BMT CTN Protocol 1301 rituximab, cyclophosphamide, doxorubicin hydrochloride (hydroxydaunomycin), vincristine R-CHOP sulfate (oncovin), prednisone RFA Request for Applications RIC reduced-intensity conditioning Reduced-Intensity Conditioning for Children and Adults with Hemophagocytic Syndromes or RICHI Selected Primary Immune Deficiencies; BMT CTN Protocol 1204 RPLS reversible posterior leukoencephalopathy syndrome RVD lenalidomide, bortezomib, and dexamethasone SCURT Sickle Cell Unrelated Transplantation; BMT CTN Protocol 0601 Stem Cell Transplantation for Multiple Myeloma Incorporating Novel Agents; BMT CTN Protocol STaMINA 0702 TCR T cell receptor TNF tumor necrosis factor

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Blood and Marrow Transplant Clinical Trials Network Progress Report 2017 Attachment D: Terms and Abbreviations

Term/ Definition Abbreviation TRM transplant-related mortality / treatment-related mortality vs. versus

214