Phase 2 trial of CPX-351, a fixed 5:1 molar ratio of cytarabine/daunorubicin, vs cytarabine/daunorubicin in older adults with untreated AML.

Autor:	Lancet JE; H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL;, Cortes JE; University of Texas MD Anderson Cancer Center, Houston, TX;, Hogge DE; British Columbia Cancer Agency, Vancouver, BC, Canada;, Tallman MS; Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, NY;, Kovacsovics TJ; Oregon Health & Science University, Knight Cancer Institute, Portland, OR;, Damon LE; University of California, San Francisco, San Francisco, CA;, Komrokji R; H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL;, Solomon SR; Blood & Marrow Transplant at Northside Hospital, Atlanta, GA;, Kolitz JE; Hofstra North Shore-Long Island Jewish School of Medicine, Lake Success, NY;, Cooper M; St. Francis Hospital and Health Centers, Indianapolis, IN;, Yeager AM; University of Arizona, Tucson, AZ;, Louie AC; Celator Pharmaceuticals, Inc., Princeton, NJ; and., Feldman EJ; Weill Medical College of Cornell University and New York Presbyterian Hospital, New York, NY.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2014 May 22; Vol. 123 (21), pp. 3239-46. Date of Electronic Publication: 2014 Mar 31.
DOI:	10.1182/blood-2013-12-540971
Abstrakt:	CPX-351 is a liposomal formulation of cytarabine:daunorubicin designed to deliver synergistic drug ratios to leukemia cells. In this phase 2 study, newly diagnosed older acute myeloid leukemia (AML) patients were randomized 2:1 to first-line CPX-351 or 7+3 treatment. The goal was to determine efficacy and identify patient subgroups that may benefit from CPX-351 treatment. Response rate (complete remission + incomplete remission) was the primary end point, with event-free survival (EFS) and overall survival (OS) as secondary end points. The 126 patients entered were balanced for disease and patient-specific risk factors. Overall, CPX-351 produced higher response rates (66.7% vs 51.2%, P = .07), meeting predefined criteria for success (P < .1). Differences in EFS and OS were not statistically significant. A planned analysis of the secondary AML subgroup demonstrated an improved response rate (57.6% vs 31.6%, P = .06), and prolongation of EFS (hazard ratio [HR] = 0.59, P = .08) and OS (HR = 0.46, P = .01). Recovery from cytopenias was slower after CPX-351 (median days to absolute neutrophil count ≥1000: 36 vs 32; platelets >100 000: 37 vs 28) with more grade 3-4 infections but without increase in infection-related deaths (3.5% vs 7.3%) or 60-day mortality (4.7% vs 14.6%), indicating acceptable safety. These results suggest a clinical benefit with CPX-351, particularly among patients with secondary AML, and provide the rationale for a phase 3 trial currently underway in newly diagnosed secondary AML patients. This study is registered at Clinicaltrials.gov as #NCT00788892. (© 2014 by The American Society of Hematology.)
Databáze:	MEDLINE
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