Relapsed or refractory, Philadelphia Chromosome-negative Acute Lymphoblastic Leukemia
- Single cycle: 4 wks of continuous IV infusion followed by a 2-week treatment-free interval
- Course of treatment: Up to 2 cycles for induction followed by 3 additional cycles for consolidation treatment i.e. up to a total of 5 cycles
45 kg- Cycle 1:
- Starting dose: On Days 1-7: 9 mcg/day via continuous IV infusion
- Subsequent dose: On Days 8-28: 28 mcg/day via continuous IV infusion
- Treatment free interval: At least 2 wks (Days 29-42)
- Cycle 2 and subsequent Cycles: On Days 1-28: 28 mcg/day via continuous IV infusion
Note:
- Hospitalization is recommended for the first 9 days of the first cycle and the first 2 days of the second cycle
- Supervision by a healthcare professional or hospitalization is recommended for all subsequent cycle starts and if the treatment is reinitiated after an interruption of 4 hrs
- DO NOT flush the infusion line; flushing the infusion line when changing bags or at completion of infusion can result in excess dosage and complications thereafter
- Premedication: Dexamethasone [IV] 20 mg, 1 hr prior to the first dose of each cycle, prior to a step dose (e.g., Cycle 1 day 8), or when restarting an infusion after an interruption of 4 hrs
- Refer package insert for instructions regarding administration as well as reconstitution and preparation of solution for infusion
- Interruption after an adverse event
7 days: Continue the same cycle to a total of 28 days of infusion inclusive of days before and after the interruption in that cycle- 7 days: Start a new cycle
- Cytokine Release Syndrome (CRS)
- Grade 3: Withhold treatment until resolved; restart at 9 mcg/day; increase dose to 28 mcg/day after 7 days if the toxicity does not recur
- Grade 4: Discontinue treatment permanently
- Neurological Toxicity
- Seizure: Discontinue treatment permanently if > 1 seizures occur
- Grade 3: Withhold treatment until Grade 1 (mild) and for at least 3 days; restart at 9 mcg/day; increase dose to 28 mcg/day after 7 days if the toxicity does not recur. If the toxicity occurred at 9 mcg/day, or if the toxicity takes > 7 days to resolve, discontinue treatment permanently
- Grade 4: Discontinue treatment permanently
- Other Clinically Relevant Adverse Reactions
- Grade 3: Withhold treatment until Grade 1 (mild); restart at 9 mcg/day; increase dose to 28 mcg/day after 7 days if the toxicity does not recur. If the toxicity takes > 14 days to resolve, discontinue treatment permanently
- Grade 4: Discontinue treatment permanently
- Elevated Liver Enzymes
- Alanine aminotransferase (ALT)/ aspartate aminotransferase (AST) > 5 x ULN or bilirubin > 3 x ULN: Interrupt treatment
- The recommended phase 2 regimen for a dose-escalation study of 41 pediatric patients (aged 2-17 yrs) with relapsed or refractory B-precursor ALL was 5 mcg/m(2)/day on Days 1-7 and 15 mcg/m(2)/day on Days 8-28 for cycle 1, and 15 mcg/m(2)/day on Days 1-28 for subsequent cycles
- A fatal cardiac failure event occurred at a higher dose, in the setting of life-threatening CRS
- The steady-state concentrations were comparable in adult and pediatric patients at equivalent doses based on body surface area (BSA)-based regimens
