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)

Purpose 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). Patients and Methods 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). Results 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. Conclusions 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.