Title: A Phase I Trial of NECTAR (Nelarabine, Etoposide and Cyclophosphamide in T-ALL Relapse): A Joint Study of TACL and POETIC

IRB# 2010-007 Principal Investigator: Jacob Garcia, MD

Synopsis: Nelarabine is a drug approved by the FDA (Food and Drug Administration) for treating children and adults with T-cell acute lymphoblastic leukemia (T-ALL) or non-hodgkins lymphoma (T-NHL). Nelarabine has been used by itself to treat children and adults with relapsed T-ALL and T-NHL. Nelarabine has not been tested in combination with the other chemotherapy drugs used in this study. In this study, researchers are doing a Phase I study. In a phase I study drugs are tested to the highest dose that can be safely given. Drugs are given at gradually increasing dosages until there are unacceptable side effects. The goal of the Phase I study is to find out the doses of nelarabine, etoposide and cyclophosphamide that can be safely given for 5 days to patients with relapsed T-ALL and T-NHL.

About 36 children and young adults will participate in this study.

The goals of this study are to: • To determine the best dose of nelarabine, etoposide and cyclophosphamide that can be safely given in combination to treat relapsed T-cell leukemia or lymphoma. • To evaluate the side effects when giving all 3 drugs together on this treatment schedule. • To evaluate the effectiveness of this combination in treating relapsed T-cell ALL or lymphoma. • To determine if children are able to have a bone marrow transplant after treatment with these 3 drugs together. • To learn about how levels of chemicals in your blood and cerebral spinal fluid (CSF) may contribute to the side effects of this treatment.

The 3 drugs (nelarabine, etoposide, and cyclophosphamide) in this study will be given through a vein once a day for 5 days in a row. Most patients will receive this therapy through their central line. The first drug, nelarabine, will be given over 1-hour. The second drug, Etoposide will be given over 2-hours. The third drug, cyclophosphamide is given over 30-60 minutes. One day after finishing the five days of treatment with these drugs, the patient will begin receiving daily injections of a drug called filgrastim (GCSF) to help blood counts recover.

All three drugs will be given once a day on Days 1 to 5. The patient will be hospitalized while receiving the study drugs to see how his/her body handles the drug treatment. After the 5 days of drugs, the patient will have a rest period for about 16-23 days before the next treatment. The total of 36 days is a “treatment course”. At the end of the treatment course, the patient will have a lumbar puncture and receive methotrexate injected into the spinal fluid.

All patients will receive the 2 courses of chemotherapy unless the treatment is not working or the patient has unacceptable side effects of the treatment. Different patients may receive different dose of Nelarabine depending when he/she enters in the study and other patients’ experience with this drug. At the end of each treatment course, the patient will have an evaluation to see how his/her leukemia or lymphoma is responding to the treatment. Treatment for the 2 courses of therapy will last about 2 and ½ months. Additional therapy is recommended after completion of this treatment and the doctor will discuss those options with the patient/family.

If you are interested in getting more information about this clinical trial, please send us an email ([email protected]).