Final results of a phase 2 trial of clofarabine and low-dose cytarabine alternating with decitabine in older patients with newly diagnosed acute myeloid leukemia.

BACKGROUND: The treatment of older adults with acute myeloid leukemia (AML) using standard intensive chemotherapy has been associated with poor outcomes. Effective, less toxic therapies are needed to achieve and maintain durable remissions.
METHODS: One hundred eighteen patients with newly diagnosed AML (median age, 68 years; range, 60-81 years) were treated with a regimen of clofarabine and low-dose cytarabine (LDAC) alternating with decitabine (DAC). The induction consisted of intravenous clofarabine at 20 mg/m(2) on days 1 to 5 combined with subcutaneous LDAC at 20 mg twice daily on days 1 to 10. Responding patients were then treated with a prolonged consolidation/maintenance regimen consisting of cycles of clofarabine plus LDAC alternating with cycles of DAC.
RESULTS: The overall response rate was 68%. The complete remission (CR) rate was 60% overall, 71% for patients with a diploid karyotype, and 50% for patients with an adverse karyotype. The median overall survival (OS) was 11.1 months for all patients and 18.5 months for those achieving a CR/complete remission with incomplete platelet recovery (CRp). The median relapse-free survival for patients achieving a CR/CRp was 14.1 months. According to a multivariate analysis, only adverse cytogenetics and a white blood cell count ≥ 10 × 10(9)/L predicted worse OS. The regimen was well tolerated with 4- and 8-week mortality rates of 3% and 7%, respectively. The most common nonhematologic adverse events were nausea, elevated liver enzymes, and rash.
CONCLUSIONS: The lower intensity, prolonged-therapy program of clofarabine and LDAC alternating with DAC is well tolerated and highly effective in older patients with AML.