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The QUAZAR AML-001 Maintenance Trial: Results of a Phase III International, Randomized, Double-Blind, Placebo-Controlled Study of CC-486 (Oral Formulation of Azacitidine) in Patients with Acute Myeloid Leukemia (AML) in First Remission
Introduction: Many older patients (pts) with AML respond to intensive induction chemotherapy (IC), but responses are often short-lived and overall survival (OS) is poor. The benefit of post-remission maintenance treatment (Tx) for pts with AML is unclear, as no therapy has shown to significantly imp...
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Published in: | Blood 2019-11, Vol.134 (Supplement_2), p.LBA-3-LBA-3 |
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Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Citations: | Items that cite this one |
Online Access: | Get full text |
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Summary: | Introduction: Many older patients (pts) with AML respond to intensive induction chemotherapy (IC), but responses are often short-lived and overall survival (OS) is poor. The benefit of post-remission maintenance treatment (Tx) for pts with AML is unclear, as no therapy has shown to significantly improve OS. CC-486 is an oral hypomethylating agent that allows for prolonged drug exposure during each Tx cycle to sustain therapeutic activity. We hypothesized that prolonged Tx with CC-486 could be effective as post-remission maintenance in AML.
Herein, we report the primary results of QUAZAR AML-001 (NCT01757535), a phase III international, randomized, double-blind, placebo (PBO)-controlled study evaluating CC-486 as maintenance therapy in pts aged ≥55 years with AML in first remission following IC.
Methods: Eligible pts had de novo or secondary AML, intermediate- or poor-risk cytogenetics, and Eastern Cooperative Oncology Group performance status (ECOG PS) scores of ≤3; had achieved first complete remission (CR) or CR with incomplete count recovery (CRi) after IC, with or without consolidation chemotherapy; and were not candidates for hematopoietic stem-cell transplant (HSCT). Within 4 months of attaining CR/CRi, pts were randomized 1:1 to receive CC-486 300 mg or PBO once-daily on days 1-14 of repeated 28-day Tx cycles. A 21-day dosing schedule was permitted for pts who experienced AML relapse with 5-15% blasts in blood or bone marrow while on-study. Tx could continue indefinitely until the presence of >15% blasts, unacceptable toxicity, or HSCT. The primary endpoint was OS. Secondary endpoints included relapse-free survival (RFS), health-related quality of life (HRQoL), and safety. Samples were collected for exploratory translational endpoints, including measurable residual disease (MRD). Kaplan-Meier estimates of OS and RFS were compared for CC-486 vs. PBO by stratified log-rank test. Hazard ratios (HRs) and 95% confidence intervals (CIs) were generated using a stratified Cox proportional hazards model.
Results: Between May 2013 and October 2017, 472 pts were randomized to receive CC-486 (n=238) or PBO (n=234). Baseline characteristics were balanced between Tx arms. Median age was 68 years (range 55-86), 91% of pts had de novo AML, and 86% and 14% of pts, respectively, had intermediate-risk or poor-risk cytogenetics. Following induction, 81% of pts achieved a CR and 19% achieved CRi; 80% of pts had received consolidation chemotherapy (45% received 1 consoli |
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ISSN: | 0006-4971 1528-0020 |
DOI: | 10.1182/blood-2019-132405 |