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.