Phase II Study of the Combination of Clofarabine Plus Idarubicin and Cytarabine (CIA) In Patients with Relapsed/Refractory Acute Myeloid Leukemia (AML).

Abstract 1061

Clofarabine is a second generation nucleoside analog with activity in patients with acute leukemias. Previous studies with the combination of clofarabine plus cytarabine have reported a complete remission rate (CR) of 24% in relapsed AML and 52% in previously untreated AML patients. To explore further combinations with drugs active in AML, we conducted a phase II study of CIA in patients with relapsed and primary refractory AML. Patients were treated at the maximum tolerated dose (MTD) determined from a preceding phase I study: clofarabine 22.5mg/m2 IV daily × 5, idarubicin 6 mg/m2 IV daily × 3, and cytarabine 0.75 g/m2 IV daily × 5 days. A total of 63 patients were enrolled. Patients with prior exposure to clofarabine were not eligible. The median age was 51years (18 - 80years). Twenty-four patients were primary refractory and 39 had relapsed disease. All the patients received CIA in 1^st salvage. For patients with relapsed AML, the median duration of the first CR was 36 weeks (3 – 215 weeks). Three patients underwent stem cell transplant (SCT) prior to treatment with CIA and 28 patients had received at least intermediate doses of cytarabine prior to relapse. Fifteen patients had secondary AML following a preceding phase of MDS. Twenty-five percent of patients had -5/-7 and 6% had trisomy 8. Thirteen patients (21%) achieved CR, 7 (11%) CRp (complete remission without platelet recovery), and 4 (6%) a partial remission (PR) for an overall response rate of 38%. The response rate in patients with primary refractory disease was 33% while the response rate in patients with relapsed disease was 41%. Five patients (8%) died during induction (</= 28 days); 4 from septic shock and 1 from diffuse alveolar hemorrhage. Median duration of follow-up was 65 weeks (range 6–161). Median overall survival was 34 weeks (range 1–161). Disease free survival for those patients who achieved CR/CRp was 66 weeks (range 4–156). A total of 24 (38%) patients underwent SCT following CIA. The most common toxicity was nausea/vomiting in 49 (78%) patients followed by hepatic dysfunction in 43 (68%) patients and diarrhea in 42 (67%) patients. In summary, the CIA combination has activity in patients with relapsed/refractory AML. Further evaluation in better prognosis patients is ongoing.