title: Phase II, multicenter, randomized trial of CPX-351 (cytarabine:daunorubicin) liposome injection versus intensive salvage therapy in adults with first relapse AML.
abstract: BACKGROUND
  CPX-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.
  
  
  METHODS
  This 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.
  
  
  RESULTS
  Patient 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%).
  
  
  CONCLUSIONS
  Taken together, the data suggest possible improved outcomes in CPX-351-treated first relapse AML patients with EPI-defined poor-risk disease.
authors.affiliation: The MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Cortes
authors.forename: Stuart L
authors.initials: SL
authors.lastname: Goldberg
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Feldman
authors.forename: David A
authors.initials: DA
authors.lastname: Rizzeri
authors.forename: Donna E
authors.initials: DE
authors.lastname: Hogge
authors.forename: Melissa
authors.initials: M
authors.lastname: Larson
authors.forename: Arnaud
authors.initials: A
authors.lastname: Pigneux
authors.forename: Christian
authors.initials: C
authors.lastname: Recher
authors.forename: Gary
authors.initials: G
authors.lastname: Schiller
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Warzocha
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Arthur C
authors.initials: AC
authors.lastname: Louie
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Kolitz
mesh_terms: D000328:Adult; D000368:Aged; D000617:Aminoglycosides / Q000008:administration & dosage; D000677:Amsacrine / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017338:Cladribine / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D000079982:Gemtuzumab; D006801:Humans; D007267:Injections; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality; D008081:Liposomes; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D012008:Recurrence; D012074:Remission Induction; D018570:Risk Assessment; D016879:Salvage Therapy / Q000379:methods*; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D000617:Aminoglycosides; D061067:Antibodies, Monoclonal, Humanized; D008081:Liposomes; D000677:Amsacrine; D003561:Cytarabine; D017338:Cladribine; D005047:Etoposide; D000079982:Gemtuzumab; D008942:Mitoxantrone; D014740:Vidarabine; C024352:fludarabine; D003630:Daunorubicin
keywords: Acute Myeloid Leukemia; Chemotherapy Intervention; First Relapse; Phase II