A phase 1b/2 study of vosaroxin in combination with cytarabine in patients with relapsed or refractory acute myeloid leukemia

Jeffrey E. Lancet, Gail J. Roboz, Larry D. Cripe, Glenn C. Michelson, Judith A. Fox, Richard D. Leavitt, Tianling Chen, Rachael Hawtin, Adam R. Craig, Farhad Ravandi, Michael B. Maris, Robert K. Stuart, Judith E. Karp

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24 Scopus citations

Abstract

Vosaroxin is a first-in-class anticancer quinolone derivative that intercalates DNA and inhibits topoisomerase II. This study assessed the safety and tolerability of vosaroxin plus cytarabine in patients with relapsed/refractory acute myeloid leukemia. Escalating vosaroxin doses (10-minute infusion; 10-90 mg/m2; days 1, 4) were given in combination with cytarabine on one of two schedules: schedule A (24-hour continuous intravenous infusion, 400 mg/m2/day, days 1-5) or schedule B (2-hour intravenous infusion, 1 g/m2/day, days 1-5). Following dose escalation, enrollment was expanded at the maximum tolerated dose. Of 110 patients enrolled, 108 received treatment. The maximum tolerated dose of vosaroxin was 80 mg/m2 for schedule A (dose-limiting toxicities: grade 3 bowel obstruction and stomatitis) and was not reached for schedule B (recommended phase 2 dose: 90 mg/m2). In the efficacy population (all patients in first relapse or with primary refractory disease treated with vosaroxin 80-90 mg/m2; n=69), the complete remission rate was 25% and the complete remission/complete remission with incomplete blood count recovery rate was 28%. The 30-day all-cause mortality rate was 2.5% among all patients treated at a dose of 80-90 mg/m2. Based upon these results, a phase 3 trial of vosaroxin plus cytarabine was initiated in patients with relapsed/refractory acute myeloid leukemia.

Original languageEnglish (US)
Pages (from-to)231-237
Number of pages7
JournalHaematologica
Volume100
Issue number2
DOIs
StatePublished - Jan 1 2015

ASJC Scopus subject areas

  • Hematology

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    Lancet, J. E., Roboz, G. J., Cripe, L. D., Michelson, G. C., Fox, J. A., Leavitt, R. D., Chen, T., Hawtin, R., Craig, A. R., Ravandi, F., Maris, M. B., Stuart, R. K., & Karp, J. E. (2015). A phase 1b/2 study of vosaroxin in combination with cytarabine in patients with relapsed or refractory acute myeloid leukemia. Haematologica, 100(2), 231-237. https://doi.org/10.3324/haematol.2014.114769