REVEAL-1, a phase 2 dose regimen optimization study of vosaroxin in older poor-risk patients with previously untreated acute myeloid leukaemia

Robert K. Stuart, Larry D. Cripe, Michael B. Maris, Maureen A. Cooper, Richard M. Stone, Shaker R. Dakhil, Francesco Turturro, Wendy Stock, James Mason, Paul J. Shami, Stephen A. Strickland, Luciano J. Costa, Gautam Borthakur, Glenn C. Michelson, Judith A. Fox, Richard D. Leavitt, Farhad Ravandi

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

This phase 2 study (N = 116) evaluated single-agent vosaroxin, a first-in-class anticancer quinolone derivative, in patients ≥60 years of age with previously untreated unfavourable prognosis acute myeloid leukaemia. Dose regimen optimization was explored in sequential cohorts (A: 72 mg/m2 d 1, 8, 15; B: 72 mg/m2 d 1, 8; C: 72 mg/m2 or 90 mg/m2 d 1, 4). The primary endpoint was combined complete remission rate (complete remission [CR] plus CR with incomplete platelet recovery [CRp]). Common (>20%) grade ≥3 adverse events were thrombocytopenia, febrile neutropenia, anaemia, neutropenia, sepsis, pneumonia, stomatitis and hypokalaemia. Overall CR and CR/CRp rates were 29% and 32%; median overall survival (OS) was 7·0 months; 1-year OS was 34%. Schedule C (72 mg/m2) had the most favourable safety and efficacy profile, with faster haematological recovery (median 27 d) and lowest incidence of aggregate sepsis (24%) and 30-d (7%) and 60-d (17%) all-cause mortality; at this dose and schedule, CR and CR/CRp rates were 31% and 35%, median OS was 7·7 months and 1-year OS was 38%. Overall, vosaroxin resulted in low early mortality and an encouraging response rate; vosaroxin 72 mg/m2 d 1, 4 is recommended for further study in this population. Registered at www.clinicaltrials.gov: #NCT00607997.

Original languageEnglish (US)
Pages (from-to)796-805
Number of pages10
JournalBritish journal of haematology
Volume168
Issue number6
DOIs
StatePublished - Mar 1 2015

Keywords

  • Acute myeloid leukaemia
  • Elderly
  • Newly diagnosed
  • Topoisomerase-II inhibitor
  • Vosaroxin

ASJC Scopus subject areas

  • Hematology

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    Stuart, R. K., Cripe, L. D., Maris, M. B., Cooper, M. A., Stone, R. M., Dakhil, S. R., Turturro, F., Stock, W., Mason, J., Shami, P. J., Strickland, S. A., Costa, L. J., Borthakur, G., Michelson, G. C., Fox, J. A., Leavitt, R. D., & Ravandi, F. (2015). REVEAL-1, a phase 2 dose regimen optimization study of vosaroxin in older poor-risk patients with previously untreated acute myeloid leukaemia. British journal of haematology, 168(6), 796-805. https://doi.org/10.1111/bjh.13214