A Phase I/II Study of Idarubicin (Ida) with Continuous Infusion Fludarabine (F-ara-A) and Cytarabine (ara-C) for Refractory or Recurrent Pediatric Acute Myeloid Leukemia (AML)

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Abstract
The goal was to conduct a phase I/II trial of escalating doses of Idarubicin (Ida) in conjunction with the previously established maximum tolerated dose (MTD) of F-ara-A/ara-C in children with refractory or recurrent acute myeloid leukemia (AML). We conducted a phase I/II trial in parallel with Children's Cancer Group (CCG) study 0922, which involved dose escalation of Ida at levels of 6 mg/m2, 9 mg/m2, and 12 mg/m2 over 15 minutes on days 0, 1, and 2. As phase I safety was documented by CCG, we increased the dose of Ida given on day 0, 1, and 2 of the F-ara-A/ ara-C infusion (F-ara-A: 10.5 mg/m2 over 15 minutes and 1.27 mg/m2/hour for 48 hours followed by ara-C: 390 mg/m2 over 15 minutes and 101 mg/m2/hour for 72 hours). Ten of 15 patients achieved remission. There was one toxic death due to adult respiratory distress syndrome. The median time to an absolute neutrophil count (ANC) > 200/μl was 29 days; ANC > 1,000/μl was 41 days; and platelets > 100,000/μl was 45 days. A dose of 12 mg/m2/day × 3 of Ida did not exceed dose-limiting toxicity with this combination of F-ara-A/ara-C. Substantial activity of this regimen was seen in pediatric patients with AML.