THE CLATTERBRIDGE CANCER CENTRE NHS FOUNDATION TRUST Systemic Anti-Cancer Treatment Protocol Mylotarg® in combination with DA Acute Myeloid Leukaemia (AML) PROTOCOL REF: MPHAMDAHA (Version No: 1.1) Approved for use in: Gemtuzumab Ozogamicin (Mylotarg®) is indicated, in combination with daunorubicin and cytarabine (DA), for the treatment of previously untreated CD33-positive Acute Myeloid Leukaemia (AML) in patients aged 15 years and over when the following conditions are met: The prescribing consultant is fully aware of the potential for Mylotarg® to induce hepatotoxicity, including veno-occlusive liver disease / sinusoidal obstruction syndrome The patient does NOT have Acute Promyelocytic Leukaemia (APML) The patient has previously untreated AML The patient is aged 15 years or over The patient starts treatment when they have had cytogenetics performed and confirmed as favourable, intermediate or unknown cytogenetics (that is, because the test was unsuccessful), or when their cytogenetic tests are not available yet. The patient is fit for intensive induction chemotherapy Mylotarg® is to be given in combination with daunorubicin and cytarabine Note this protocol should only be used to treat patients off-trial. Refer to relevant trial protocol for enrolled patients. Exempt from NHS England treatment break policy Blueteq registration required for Mylotarg® Issue Date: 13th March 2020 Page 1 of 14 Protocol reference: MPHAMDAHA Review: March 2023 Author: Niamh McLaughlin Authorised by: Drug & Therapeutics Committee Version No: 1.1 THE CLATTERBRIDGE CANCER CENTRE NHS FOUNDATION TRUST Dosage: Treatment Drug Dosage Route Frequency course 2 Mylotarg® 3 mg/m /dose IV Days 1,4 and 7 (max 5mg/dose) First 2 Induction Daunorubicin 60 mg/m /day IV Days 1-3 Cytarabine 200 mg/m2/day IV Days 1-7 Mylotarg® should not be administered during second induction Second 2 induction Daunorubicin 35 mg/m /day IV Days 1-2 (if required)* Every 12 hours on days Cytarabine 1000 mg/m2/dose IV 1-3 2 Mylotarg® 3 mg/m /dose IV On day 1 only (max 5mg/dose) Consolidation Daunorubicin 60 mg/m2/day IV On day 1 only course 1** Every 12 hours on days Cytarabine 1000 mg/m2/dose IV 1-4 2 Mylotarg® 3 mg/m /dose IV On day 1 only (max 5mg/dose) Consolidation Daunorubicin 60 mg/m2/day IV Days 1and 2 course 2 Every 12 hours on days Cytarabine 1000 mg/m2/dose IV 1-4 *If residual disease on D14 bone marrow biopsy **For patients experiencing a complete remission (CR) following induction, defined as fewer than 5% blasts in a normocellular marrow and an absolute neutrophil count (ANC) >1.0 × 109 cells/L with a platelet count of ≥100 × 109/L in the peripheral blood in the absence of transfusion, up to 2 consolidation courses can be given. Schedule modification for hyperleukocytosis: If leukocyte count ≥30x109/L, cyto-reduction is recommended 48 hours prior to commencing Mylotarg ® in order to reduce the peripheral white cell count. See recommended changes to induction schedule below. Options for cyto-reduction include: Issue Date: 13th March 2020 Page 2 of 14 Protocol reference: MPHAMDAHA Review: March 2023 Author: Niamh McLaughlin Authorised by: Drug & Therapeutics Committee Version No: 1.1 THE CLATTERBRIDGE CANCER CENTRE NHS FOUNDATION TRUST Leukapheresis. Oral hydroxycarbamide. Cytarabine +/- hydroxycarbamide If Cytarabine is used for leukoreduction, (with or without hydroxycarbamide); in patients with previously untreated de novo hyperleukocytic AML, receiving Mylotarg® in combination therapy, apply the following modified schedule for the first induction cycle: Treatment Drug Dosage Route Frequency course 2 Mylotarg® 3 mg/m /dose IV Days 3,6 and 9 (max 5mg/dose) Daunorubicin 60 mg/m2/day IV Days 3-5 Induction Cytarabine 200 mg/m2/day IV Days 1-7 Hydroxyurea 40-60mg/kg/day PO Day 1 Supportive treatments: 1. Premedication with a corticosteroid, antihistamine, and paracetamol is necessary 1 hour prior to Mylotarg® to help ameliorate infusion-related symptoms 2. Anti-hyperuricaemic treatment as per trust tumour lysis policy 3. Anti-emetics as per Trust chemotherapy-induced nausea and vomiting policy 4. Anti-microbials as per Trust Antimicrobial prophylaxis policy 5. Corticosteroid eye drops QDS for duration of treatment and for five days after (second induction and consolidation cycles only) Consider avoiding posaconazole and other azoles while on Mylotarg® and for five days after Mylotarg® treatment has finished. AML 19 clinical trial protocol recommends this owing to potential risk of hepatotoxicity, but Mylotarg® SPC makes no reference to this risk, so clinical judgement should be used. Use Caspofungin as an alternative to azole prophylaxis if required. Issue Date: 13th March 2020 Page 3 of 14 Protocol reference: MPHAMDAHA Review: March 2023 Author: Niamh McLaughlin Authorised by: Drug & Therapeutics Committee Version No: 1.1 THE CLATTERBRIDGE CANCER CENTRE NHS FOUNDATION TRUST Cautions Hypotension may occur, therefore it is advisable to withhold anti-hypertensive medications 12hours before and 12 hours after treatment with Mylotarg® Adverse risk cytogenetics Moderate/severe hepatic impairment: increased risk of veno-occlusive disease Concomitant use of cardiotoxic agents Pregnant/breastfeeding Extravasation Risk: 1. Daunorubicin- vesicant 2. Cytarabine- non-vesicant 3. Mylotarg®- unknown Refer to the CCC policy for the ‘Prevention and Management of Extravasation Injuries’ Administration: Do not give other drugs through the same infusion line as Mylotarg® Day Drug Dosage Route Diluent and Rate Induction Cycle 1 Diluted in 100ml NaCl 0.9% Hydrocortisone 100mg IV over 30 minutes Chlorphenamine 10mg IV IV Stat Paracetamol 1000mg PO Oral Stat Day 1 In 50ml 0.9% sodium 2 IV chloride over 2 hours, via Mylotarg®* 3mg/m (max 5mg) infusion low-protein binding 0.2 micron filter. Monitor vital signs during Mylotarg® infusion and for 4 hours after Issue Date: 13th March 2020 Page 4 of 14 Protocol reference: MPHAMDAHA Review: March 2023 Author: Niamh McLaughlin Authorised by: Drug & Therapeutics Committee Version No: 1.1 THE CLATTERBRIDGE CANCER CENTRE NHS FOUNDATION TRUST In 100ml 0.9% sodium Daunorubicin 60mg/m2 IV chloride given over 30mins In 1000ml 0.9% sodium Cytarabine 200mg/m2 IV chloride given over 22hours In 100ml 0.9% sodium Daunorubicin 60mg/m2 IV chloride given over 30mins Day 2 In 1000ml 0.9% sodium Cytarabine 200mg/m2 IV chloride given over 22hours In 100ml 0.9% sodium Daunorubicin 60mg/m2 IV chloride given over 30mins Day 3 In 1000ml 0.9% sodium Cytarabine 200mg/m2 IV chloride given over 22hours Diluted in 100ml NaCl 0.9% Hydrocortisone 100mg IV over 30 minutes Chlorphenamine 10mg IV IV Stat Paracetamol 1000mg PO Oral Stat In 50ml 0.9% sodium Day 4 2 IV chloride over 2 hours, via Mylotarg®* 3mg/m (max 5mg) infusion low-protein binding 0.2 micron filter. Monitor vital signs during Mylotarg® infusion and for 4 hours after In 1000ml 0.9% sodium Cytarabine 200mg/m2 IV chloride given over 22hours In 1000ml 0.9% sodium Day 5 Cytarabine 200mg/m2 IV chloride given over 22hours In 1000ml 0.9% sodium Day 6 Cytarabine 200mg/m2 IV chloride given over 22hours Diluted in 100ml NaCl 0.9% Hydrocortisone 100mg IV over 30 minutes Chlorphenamine 10mg IV IV Stat Paracetamol 1000mg PO Oral Stat In 50ml 0.9% sodium Day 7 Mylotarg®* 3mg/m2 IV chloride over 2 hours, via (Only for Induction 1) (max 5mg) infusion low-protein binding 0.2 micron filter. Monitor vital signs during Mylotarg® infusion and for 4 hours after In 1000ml 0.9% sodium Cytarabine 200mg/m2 IV chloride given over 22hours Induction cycle 2 (If required. No Mylotarg®) In 100ml 0.9% sodium Day 1 Daunorubicin 35mg/m2 IV chloride given over 30mins Issue Date: 13th March 2020 Page 5 of 14 Protocol reference: MPHAMDAHA Review: March 2023 Author: Niamh McLaughlin Authorised by: Drug & Therapeutics Committee Version No: 1.1 THE CLATTERBRIDGE CANCER CENTRE NHS FOUNDATION TRUST In 500ml 0.9% sodium 1100 Cytarabine 1000mg/m2 IV chloride given over 2 hours In 500ml 0.9% sodium 2300 Cytarabine 1000mg/m2 IV chloride given over 2 hours In 100ml 0.9% sodium Daunorubicin 35mg/m2 IV chloride given over 30mins In 500ml 0.9% sodium Day 2 1100 Cytarabine 1000mg/m2 IV chloride given over 2 hours In 500ml 0.9% sodium 2300 Cytarabine 1000mg/m2 IV chloride given over 2 hours In 500ml 0.9% sodium 1100 Cytarabine 1000mg/m2 IV chloride given over 2 hours Day 3 In 500ml 0.9% sodium 2300 Cytarabine 1000mg/m2 IV chloride given over 2 hours Consolidation Cycle 1 Diluted in 100ml NaCl Hydrocortisone 100mg IV 0.9% over 30 minutes Chlorphenamine 10mg IV IV Stat Paracetamol 1000mg PO Oral Stat In 50ml 0.9% sodium 3mg/m2 IV chloride over 2 hours, via Mylotarg®* (max 5mg) infusion low-protein binding 0.2 Day 1 micron filter. Monitor vital signs during Mylotarg® infusion and for 4 hours after In 100ml 0.9% sodium Daunorubicin 60mg/m2 IV chloride given over 30mins In 500ml 0.9% sodium 1100 Cytarabine 1000mg/m2 IV chloride given over 2 hours In 500ml 0.9% sodium 2300 Cytarabine 1000mg/m2 IV chloride given over 2 hours In 500ml 0.9% sodium 1100 Cytarabine 1000mg/m2 IV chloride given over 2 hours Day 2 In 500ml 0.9% sodium 2300 Cytarabine 1000mg/m2 IV chloride given over 2 hours In 500ml 0.9% sodium 1100 Cytarabine 1000mg/m2 IV chloride given over 2 hours Day 3 In 500ml 0.9% sodium 2300 Cytarabine 1000mg/m2 IV chloride given over 2 hours In 500ml 0.9% sodium Day 4 1100 Cytarabine 1000mg/m2 IV chloride given over 2 hours Issue Date: 13th March 2020 Page 6 of 14 Protocol reference: MPHAMDAHA Review: March 2023 Author: Niamh McLaughlin Authorised by: Drug & Therapeutics Committee Version No: 1.1 THE CLATTERBRIDGE CANCER CENTRE NHS FOUNDATION TRUST In 500ml 0.9% sodium 2300 Cytarabine 1000mg/m2 IV chloride given over 2 hours Consolidation Cycle 2 Diluted in 100ml NaCl Hydrocortisone 100mg IV 0.9% over 30 minutes Chlorphenamine 10mg IV IV Stat Paracetamol 1000mg PO Oral Stat In 50ml 0.9% sodium 3mg/m2 IV chloride over 2 hours, via Mylotarg®* (max 5mg) infusion low-protein binding 0.2 Day 1 micron filter.