Abstract
BACKGROUND: Outcome of patients with relapsed acute myeloid leukemia (AML) remains unsatisfactory. Clofarabine is a nucleoside analog with activity in adult AML. Combinations with cytarabine in AML are feasible and effective. Idarubicin is another active AML drug, which has not yet been tested with clofarabine. METHODS: The authors therefore designed a phase I study of clofarabine +/- cytarabine, plus idarubicin. Patients with primary refractory or first-relapse AML were assigned to either clofarabine plus idarubicin (CI) if previously exposed to cytarabine with a response lasting <12 months, or clofarabine and idarubicin plus cytarabine (CIA) for responses > or = 12 months, or if never exposed to cytarabine. A standard "3 + 3" phase 1 design was followed to define maximum tolerated dose (MTD). Forty-four patients were treated (23 CI; 21 CIA). RESULTS: Dose-limiting toxicities were hyperbilirubinemia and hepatic transaminase elevations for CI-treated patients in addition to mucositis and diarrhea for CIA-treated patients. MTD for CI was clofarabine 22.5 mg/m(2) intravenously daily x 5 and idarubicin 10 mg/m(2) intravenously daily x 3. MTD for CIA was clofarabine 22.5 mg/m(2) intravenously x 5, idarubicin 6 mg/m(2) intravenously x 3, and cytarabine 0.75 g/m(2) intravenously x 5 days. CONCLUSIONS: A phase 2 randomized trial is in process to compare activity between treatment arms.