Phase II, Multicenter, Randomized Trial of CPX-351 (cytarabine: daunorubicin) Liposome Injection Versus Intensive Salvage Therapy in Adults With First Relapse AML

BACKGROUNDCPX-351 is a liposome-encapsulated fixed-molar-ratio formulation of cytarabine and daunorubicin that exploits molar ratio-dependent drug-drug synergy to enhance antileukemic efficacy. METHODSThis phase II study randomized 125 patients 2:1 to CPX-351 or investigators' choice of first salvage chemotherapy. Patients with acute myeloid leukemia (AML) in first relapse after initial Complete Remission (CR) lasting 1 month were stratified per the European Prognostic Index (EPI) into favorable, intermediate, and poor-risk groups based on duration of first CR, cytogenetics, age, and transplant history. Control salvage treatment was usually based on cytarabine and anthracycline, often with 1 or more additional agents. Survival at 1 year was the primary efficacy end point. RESULTSPatient characteristics were well balanced between the 2 study arms. Improvements in efficacy outcomes were observed following CPX-351, but did not meet prospectively defined statistical criteria for 1-year survival improvement in the overall population. Subset analyses of the EPI-defined poor-risk strata demonstrated higher response rates (39.3% vs 27.6%) and improvements in event-free survival (HR, 0.63; P=.08) and overall survival (HR, 0.55; P=.02). Also, 60-day mortality was lower in the CPX-351 study arm for poor-risk patients (16.1% vs 24.1%). CONCLUSIONSTaken together, the data suggest possible improved outcomes in CPX-351-treated first relapse AML patients with EPI-defined poor-risk disease. Cancer 2015;121:234-42. (c) 2014 American Cancer Society. CPX-351, a liposome-encapsulated fixed-molar-ratio formulation of cytarabine and daunorubicin, exploits molar ratio-dependent drug-drug synergy to enhance antileukemic efficacy. A randomized phase II study comparing CPX-351 with investigators' choice of first salvage therapy in first-relapse patients demonstrated improved response, event-free survival, and overall survival (HR, 0.55; P=.02) in the poor-risk strata.