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 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 Citations (Scopus)

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 - 2015

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Cytarabine
Acute Myeloid Leukemia
Appointments and Schedules
Maximum Tolerated Dose
Intravenous Infusions
Type II DNA Topoisomerase
Stomatitis
Quinolones
vosaroxin
Safety
Recurrence
Mortality
Population

ASJC Scopus subject areas

  • Hematology

Cite this

A phase 1b/2 study of vosaroxin in combination with cytarabine in patients with relapsed or refractory acute myeloid leukemia. / Lancet, Jeffrey E.; Roboz, Gail J.; Cripe, Larry; Michelson, Glenn C.; Fox, Judith A.; Leavitt, Richard D.; Chen, Tianling; Hawtin, Rachael; Craig, Adam R.; Ravandi, Farhad; Maris, Michael B.; Stuart, Robert K.; Karp, Judith E.

In: Haematologica, Vol. 100, No. 2, 2015, p. 231-237.

Research output: Contribution to journalArticle

Lancet, JE, Roboz, GJ, Cripe, L, Michelson, GC, Fox, JA, Leavitt, RD, Chen, T, Hawtin, R, Craig, AR, Ravandi, F, Maris, MB, Stuart, RK & Karp, JE 2015, 'A phase 1b/2 study of vosaroxin in combination with cytarabine in patients with relapsed or refractory acute myeloid leukemia', Haematologica, vol. 100, no. 2, pp. 231-237. https://doi.org/10.3324/haematol.2014.114769
Lancet, Jeffrey E. ; Roboz, Gail J. ; Cripe, Larry ; Michelson, Glenn C. ; Fox, Judith A. ; Leavitt, Richard D. ; Chen, Tianling ; Hawtin, Rachael ; Craig, Adam R. ; Ravandi, Farhad ; Maris, Michael B. ; Stuart, Robert K. ; Karp, Judith E. / A phase 1b/2 study of vosaroxin in combination with cytarabine in patients with relapsed or refractory acute myeloid leukemia. In: Haematologica. 2015 ; Vol. 100, No. 2. pp. 231-237.
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AU - Fox, Judith A.

AU - Leavitt, Richard D.

AU - Chen, Tianling

AU - Hawtin, Rachael

AU - Craig, Adam R.

AU - Ravandi, Farhad

AU - Maris, Michael B.

AU - Stuart, Robert K.

AU - Karp, Judith E.

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