Interim results of a phase I/II randomized study of clofarabine, idarubicin, and cytarabine (CIA) versus fludarabine, idarubicin, and cytarabine (FIA) for newly diagnosed or relapsed patients (pts) with acute myeloid leukemia (AML).

Abstract

6607 Background: Outcomes of pts with AML remain suboptimal. The addition of cladribine to 3+7 has been shown to improve complete remission (CR) rates and 3-year survival. The aim of this study was to assess the efficacy and safety of idarubicin + cytarabine (IA, idarubicin 10 mg/m2 on days 1-3, cytarabine 1 g/m2 on days 1-5) combined with two other nucleoside analogs, clofarabine (C) or fludarabine (F), in pts with newly diagnosed and relapsed/refractory (RR) AML. Methods: Pts with newly diagnosed or RR non-M3 AML with normal organ function were eligible. Pts with RR disease were treated in the phase I portion defining the MTD of C. The starting dose of C was 15 mg/m2 with doses escalating to 25 mg/m2 on days 1-5 in subsequent cohorts. During phase II, patients were randomized in a Bayesian design to C at the MTD with IA or fludarabine (F) at 30 mg/m2 on days 1-5 with IA. Up to 6 consolidation cycles were planned according to an attenuated schedule using the same drugs. Dose adjustments were made for elderly pts or pts with poor PS. Results: 9 pts were enrolled in the phase I portion. The overall response rate (ORR) in this group was 44%. DLT were observed at C 20 mg/m2 and included hand/foot syndrome (HFS), elevated bilirubin, and prolonged myelosuppression. The MTD was 15 mg/m2 on days 1-5. 50 evaluable pts were enrolled (16 newly diagnosed, 34 RR) in the phase II. In the frontline cohort, median age was similar in both groups (C 56, F 55), as were the cytogenetic profiles. The CR rate was 100% in both groups (9 CIA, 7 FIA). Detailed efficacy information can be found in the Table. More than half of the RR cohort were receiving therapy as salvage 2 or higher, and most had short first CR durations. Notable toxicities included elevated liver function tests for both groups, and HFS in the C group. There were 4 deaths on study, though most pts were receiving therapy as second salvage and were over the age of 60. Conclusions: CIA and FIA are effective regimens for newly diagnosed or RR AML with manageable toxicity profiles. The ORR were 100% and 32% for newly diagnosed and RR AML pts, respectively, with low early mortality rates. The study is ongoing.