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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.

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.

SUBMITTER: Stuart RK

PROVIDER: S-EPMC4354261 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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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.

Stuart Robert K RK Cripe Larry D LD Maris Michael B MB Cooper Maureen A MA Stone Richard M RM Dakhil Shaker R SR Turturro Francesco F Stock Wendy W Mason James J Shami Paul J PJ Strickland Stephen A SA Costa Luciano J LJ Borthakur Gautam G Michelson Glenn C GC Fox Judith A JA Leavitt Richard D RD Ravandi Farhad F

British journal of haematology 20141117 6

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]). C ...[more]

PMID: 25403830

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Project description:PURPOSE:Effective treatment options are limited for patients with acute myeloid leukemia (AML) who cannot tolerate intensive chemotherapy. An international phase Ib/II study evaluated the safety and preliminary efficacy of venetoclax, a selective B-cell leukemia/lymphoma-2 inhibitor, together with low-dose cytarabine (LDAC) in older adults with AML. PATIENTS AND METHODS:Adults 60 years or older with previously untreated AML ineligible for intensive chemotherapy were enrolled. Prior treatment of myelodysplastic syndrome, including hypomethylating agents (HMA), was permitted. Eighty-two patients were treated at the recommended phase II dose: venetoclax 600 mg per day orally in 28-day cycles, with LDAC (20 mg/m2 per day) administered subcutaneously on days 1 to 10. Key end points were tolerability, safety, response rates, duration of response (DOR), and overall survival (OS). RESULTS:Median age was 74 years (range, 63 to 90 years), 49% had secondary AML, 29% had prior HMA treatment, and 32% had poor-risk cytogenetic features. Common grade 3 or greater adverse events were febrile neutropenia (42%), thrombocytopenia (38%), and WBC count decreased (34%). Early (30-day) mortality was 6%. Fifty-four percent achieved complete remission (CR)/CR with incomplete blood count recovery (median time to first response, 1.4 months). The median OS was 10.1 months (95% CI, 5.7 to 14.2), and median DOR was 8.1 months (95% CI, 5.3 to 14.9 months). Among patients without prior HMA exposure, CR/CR with incomplete blood count recovery was achieved in 62%, median DOR was 14.8 months (95% CI, 5.5 months to not reached), and median OS was 13.5 months (95% CI, 7.0 to 18.4 months). CONCLUSION:Venetoclax plus LDAC has a manageable safety profile, producing rapid and durable remissions in older adults with AML ineligible for intensive chemotherapy. High remission rate and low early mortality combined with rapid and durable remission make venetoclax and LDAC an attractive and novel treatment for older adults not suitable for intensive chemotherapy.

Dataset Information

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

Publications

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

Similar Datasets

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