title: Phase 2 trial of CPX-351, a fixed 5:1 molar ratio of cytarabine/daunorubicin, vs cytarabine/daunorubicin in older adults with untreated AML.
abstract: 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.
authors.affiliation: H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL;
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Lancet
authors.affiliation: University of Texas MD Anderson Cancer Center, Houston, TX;
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Cortes
authors.affiliation: British Columbia Cancer Agency, Vancouver, BC, Canada;
authors.forename: Donna E
authors.initials: DE
authors.lastname: Hogge
authors.affiliation: Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, NY;
authors.forename: Martin S
authors.initials: MS
authors.lastname: Tallman
authors.affiliation: Oregon Health & Science University, Knight Cancer Institute, Portland, OR;
authors.forename: Tibor J
authors.initials: TJ
authors.lastname: Kovacsovics
authors.affiliation: University of California, San Francisco, San Francisco, CA;
authors.forename: Lloyd E
authors.initials: LE
authors.lastname: Damon
authors.affiliation: H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL;
authors.forename: Rami
authors.initials: R
authors.lastname: Komrokji
authors.affiliation: Blood & Marrow Transplant at Northside Hospital, Atlanta, GA;
authors.forename: Scott R
authors.initials: SR
authors.lastname: Solomon
authors.affiliation: Hofstra North Shore-Long Island Jewish School of Medicine, Lake Success, NY;
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Kolitz
authors.affiliation: St. Francis Hospital and Health Centers, Indianapolis, IN;
authors.forename: Maureen
authors.initials: M
authors.lastname: Cooper
authors.affiliation: University of Arizona, Tucson, AZ;
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Yeager
authors.affiliation: Celator Pharmaceuticals, Inc., Princeton, NJ; and.
authors.forename: Arthur C
authors.initials: AC
authors.lastname: Louie
authors.affiliation: Weill Medical College of Cornell University and New York Presbyterian Hospital, New York, NY.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Feldman
mesh_terms: D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003630:Daunorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy; D008081:Liposomes; D008297:Male; D008875:Middle Aged
chemical_list: D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D008081:Liposomes; D003561:Cytarabine; D003630:Daunorubicin