1. Phase II, multicenter, randomized trial of CPX-351 (cytarabine:daunorubicin) liposome injection versus intensive salvage therapy in adults with first relapse AML
- Author
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Cortes, Jorge E, Goldberg, Stuart L, Feldman, Eric J, Rizzeri, David A, Hogge, Donna E, Larson, Melissa, Pigneux, Arnaud, Recher, Christian, Schiller, Gary, Warzocha, Krzysztof, Kantarjian, Hagop, Louie, Arthur C, and Kolitz, Jonathan E
- Subjects
Amsacrine ,Adult ,Male ,Myeloid ,Acute Myeloid Leukemia ,Pediatric Cancer ,Childhood Leukemia ,Clinical Trials and Supportive Activities ,Oncology and Carcinogenesis ,Kaplan-Meier Estimate ,Acute ,Chemotherapy Intervention ,Risk Assessment ,Disease-Free Survival ,Antibodies ,Injections ,Rare Diseases ,Recurrence ,Clinical Research ,Antineoplastic Combined Chemotherapy Protocols ,Monoclonal ,Humans ,Oncology & Carcinogenesis ,Humanized ,Etoposide ,Aged ,Cancer ,Salvage Therapy ,Pediatric ,Leukemia ,First Relapse ,Daunorubicin ,Remission Induction ,Cytarabine ,Evaluation of treatments and therapeutic interventions ,Hematology ,Middle Aged ,Gemtuzumab ,Phase II ,Aminoglycosides ,Treatment Outcome ,6.1 Pharmaceuticals ,Liposomes ,Public Health and Health Services ,Cladribine ,Female ,Mitoxantrone ,Vidarabine - Abstract
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.
- Published
- 2015