A phase II study of continuous infusion homoharringtonine and cytarabine in newly diagnosed patients with chronic myeloid leukemia: CALGB study 19804

Background Both homoharringtonine (HHT), an alkaloid derivative from the Chinese yew tree that inhibits protein synthesis, and low-dose cytarabine have independent activity in CML and have been used in combination after failure of interferon therapy. Patients and methods The CALGB performed a phase II trial of HHT (2.5 mg/m 2 per day) plus cytarabine (7.5 mg/m 2 per day), given together via continuous intravenous infusion for 7 days in previously untreated patients with Ph chromosome positive chronic phase CML. HHT/cytarabine cycles were repeated every 28 days if the blood counts were adequate. The primary endpoint was the major cytogenetic response rate after 9 months. Results Forty of the 44 enrolled patients required reduction in the infusion duration during at least one cycle. Myelosuppression was common; 66% developed neutrophil count <500/μl, but grade 3 infections occurred in only 7%. Thirty-six of 44 patients (82%) achieved a complete hematologic remission; the median duration has not been reached. Only 4 of the 23 patients (17%) having adequate cytogenetic response assessment achieved a major response within nine cycles. Conclusions Although HHT/cytarabine was generally well tolerated, the cytogenetic response rate did not exceed the level previously seen in patients with interferon-refractory CML and was not nearly as high as associated with imatinib in newly diagnosed patients.