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, 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

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/m(2) d 1, 8, 15; B: 72 mg/m(2) d 1, 8; C: 72 mg/m(2) or 90 mg/m(2) 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/m(2) ) 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/m(2) d 1, 4 is recommended for further study in this population. Registered at www.clinicaltrials.gov: #NCT00607997.

Keywords: acute myeloid leukaemia; elderly; newly diagnosed; topoisomerase-II inhibitor; vosaroxin.

© 2014 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Survival outcomes in newly diagnosed acute myeloid leukaemia treated with vosaroxin. (A) Overall survival in the pooled population (N = 113). (B) Leukaemia-free survival in patients with CR/CRp (n = 36). Sch, schedule; CR, complete remission; CRp, complete remission with incomplete platelet recovery; 95% CI, 95% confidence interval.

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