Phase I/II Study of Clofarabine, Etoposide, and Mitoxantrone in Patients With Refractory or Relapsed Acute Leukemia

Clofarabine, a second-generation nucleoside analogue, was studied in combination with etoposide and mitoxantrone in acute leukemia.In the phase I portion of this study clofarabine was given 20 or 25 mg/m(2) daily for 5 days (Days 2-6) with etoposide 100 mg/m(2) from day 1 to 5 and mitoxantrone 8 mg/m(2) from day 1 to 3. The dose-limiting toxicity was myelosuppression, and dose level 1, with clofarabine 20 mg/m(2) daily for 5 days was identified as the phase 2 dose. In total, 22 patients with relapsed or refractory acute myeloid leukemia (n = 18) and acute lymphocytic leukemia (n = 4) were treated.Five of 22 patients (23%) achieved complete response (CR), and 3 (13%) achieved CR with incomplete platelet recovery; an overall response rate of 36%. Median overall survival was 167 days (range, 22-1327 days). For 2 patients this regimen represented an effective bridge to allogeneic stem cell transplantation.Clofarabine in combination with etoposide and mitoxantrone is tolerable and shows significant activity in relapsed and refractory acute leukemia in adults.