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: Jorge E Cortes, Stuart L Goldberg, Eric J Feldman, David A Rizzeri, Donna E Hogge, Melissa Larson, Arnaud Pigneux, Christian Recher, Gary Schiller, Krzysztof Warzocha, Hagop Kantarjian, Arthur C Louie, Jonathan E Kolitz
• Journal: Cancer (Cancer) Vol. 121 Issue 2 Pg. 234-42 (Jan 15 2015) ISSN: 1097-0142 [Electronic] United States
• PMID: 25223583 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 American Cancer Society.

Chemical References

• Aminoglycosides
• Antibodies, Monoclonal, Humanized
• Liposomes
• Amsacrine
• Cytarabine
• Cladribine
• Etoposide
• Gemtuzumab
• Mitoxantrone
• Vidarabine
• fludarabine
• Daunorubicin

Topics

• Adult
• Aged
• Aminoglycosides (administration & dosage)
• Amsacrine (administration & dosage)
• Antibodies, Monoclonal, Humanized (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Cladribine (administration & dosage)
• Cytarabine (administration & dosage)
• Daunorubicin (administration & dosage)
• Disease-Free Survival
• Etoposide (administration & dosage)
• Female
• Gemtuzumab
• Humans
• Injections
• Kaplan-Meier Estimate
• Leukemia, Myeloid, Acute (drug therapy, mortality)
• Liposomes
• Male
• Middle Aged
• Mitoxantrone (administration & dosage)
• Recurrence
• Remission Induction
• Risk Assessment
• Salvage Therapy (methods)
• Treatment Outcome
• Vidarabine (administration & dosage, analogs & derivatives)