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REVEAL ‐1, a phase 2 dose regimen optimization study of vosaroxin in older poor‐risk patients with previously untreated acute myeloid leukaemia
Author(s) -
Stuart Robert K.,
Cripe Larry D.,
Maris Michael B.,
Cooper Maureen A.,
Stone Richard M.,
Dakhil Shaker R.,
Turturro Francesco,
Stock Wendy,
Mason James,
Shami Paul J.,
Strickland Stephen A.,
Costa Luciano J.,
Borthakur Gautam,
Michelson Glenn C.,
Fox Judith A.,
Leavitt Richard D.,
Ravandi Farhad
Publication year - 2015
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.13214
Subject(s) - medicine , neutropenia , gastroenterology , regimen , sepsis , febrile neutropenia , population , adverse effect , surgery , toxicity , environmental health
Summary 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 [ CR p]). Common (>20%) grade ≥3 adverse events were thrombocytopenia, febrile neutropenia, anaemia, neutropenia, sepsis, pneumonia, stomatitis and hypokalaemia. Overall CR and CR / CR p 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 / CR p 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 : # NCT 00607997.