Phase I/II study of clofarabine, etoposide, and mitoxantrone in patients with refractory or relapsed acute leukemia

Clofarabine was studied as therapy for patients with relapsed, and refractory acute leukemias in phase 1-2 dose escalation with mitoxantrone and etoposide,. A tolerable dose was identified which resulted in an overall response of 36%, and median overall survival (OS) of 167 days. This combination is active in a patient population without good standard therapy and merits further study. Background: Clofarabine, a second-generation nucleoside analogue, was studied in combination with etoposide and mitoxantrone in acute leukemia. Patients and Methods: In the phase I portion of this study clofarabine was given 20 or 25 mg/m² daily for 5 days (Days 2-6) with etoposide 100 mg/m² from day 1 to 5 and mitoxantrone 8 mg/m² from day 1 to 3. The dose-limiting toxicity was myelosuppression, and dose level 1, with clofarabine 20 mg/m² 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. Results: 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. Conclusion: Clofarabine in combination with etoposide and mitoxantrone is tolerable and shows significant activity in relapsed and refractory acute leukemia in adults.