Objective: There are limited treatment options for relapsed/refractory acute myeloid leukemia patients or previously untreated elderly (≥60 years) patients with acute myeloid leukemia. In Phase II studies from the USA and Europe, single-agent clofarabine demonstrated activity and acceptable toxicity in elderly patients with previously untreated acute myeloid leukemia. This Phase I, multicenter study assessed the maximum-tolerated dose, safety, pharmacokinetics and efficacy of clofarabine in Japanese adults with acute myeloid leukemia.
Methods: Intravenous clofarabine (20, 30 and 40 mg/m(2)/day) was administered for 5 days to Japanese adult patients with relapsed or refractory acute myeloid leukemia or elderly patients with newly diagnosed acute myeloid leukemia.
Results: Fourteen patients, median age of 67.5 (59-72) years, were enrolled in this study. Eleven out of 14 patients had relapsed/refractory acute myeloid leukemia. Three patients received clofarabine at 20 mg/m(2), six at 30 mg/m(2) and five at 40 mg/m(2). Frequently reported treatment-related adverse events included thrombocytopenia (100%), anemia (93%), neutropenia (86%), nausea (86%), alanine aminotransferase increase (71%), headache (71%) and febrile neutropenia (57%). Three patients experienced reversible dose-limiting toxicities; two had increased alanine aminotransferase with 30 and 40 mg/m(2) and one had Grade 3 elevation of serum amylase with 40 mg/m(2). The maximum-tolerated dose was 30 mg/m(2)/day. Cmax and exposure area under the curve0-24h increased with increasing dose and were proportional to dose through the tested dose range. Among the 14 assessable patients, four (29%) achieved complete remission and two (14%) complete remission without platelet recovery. The overall remission rate was 43%.
Conclusions: These results demonstrate safety and preliminary, promising activity of clofarabine in Japanese patients with acute myeloid leukemia. Further investigation is warranted.
Keywords: Phase I; acute; aged; clinical trial; clofarabine; myeloid leukemia.