Phase II, multicenter, randomized trial of CPX-351 (cytarabine:Daunorubicin) liposome injection versus intensive salvage therapy in adults with first relapse AML

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)234-242
Number of pages9
JournalCancer
Volume121
Issue number2
DOIs
StatePublished - Jan 15 2015
Externally publishedYes

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Salvage Therapy
Daunorubicin
Cytarabine
Acute Myeloid Leukemia
Liposomes
Multicenter Studies
Recurrence
Injections
Survival
Arm
Anthracyclines
Cytogenetics
Pharmaceutical Preparations
Disease-Free Survival
History
Research Personnel
Transplants
Drug Therapy
Mortality
Population

Keywords

  • Acute myeloid leukemia
  • Chemotherapy intervention
  • First relapse
  • Phase II

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Phase II, multicenter, randomized trial of CPX-351 (cytarabine:Daunorubicin) liposome injection versus intensive salvage therapy in adults with first relapse AML. / 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.; Kolitz, Jonathan E.

In: Cancer, Vol. 121, No. 2, 15.01.2015, p. 234-242.

Research output: Contribution to journalArticle

Cortes, JE, Goldberg, SL, Feldman, EJ, Rizzeri, DA, Hogge, DE, Larson, M, Pigneux, A, Recher, C, Schiller, G, Warzocha, K, Kantarjian, H, Louie, AC & Kolitz, JE 2015, 'Phase II, multicenter, randomized trial of CPX-351 (cytarabine:Daunorubicin) liposome injection versus intensive salvage therapy in adults with first relapse AML', Cancer, vol. 121, no. 2, pp. 234-242. https://doi.org/10.1002/cncr.28974
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. ; Kolitz, Jonathan E. / Phase II, multicenter, randomized trial of CPX-351 (cytarabine:Daunorubicin) liposome injection versus intensive salvage therapy in adults with first relapse AML. In: Cancer. 2015 ; Vol. 121, No. 2. pp. 234-242.
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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.",
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T1 - Phase II, multicenter, randomized trial of CPX-351 (cytarabine:Daunorubicin) liposome injection versus intensive salvage therapy in adults with first relapse AML

AU - Cortes, Jorge E.

AU - Goldberg, Stuart L.

AU - Feldman, Eric J.

AU - Rizzeri, David A.

AU - Hogge, Donna E.

AU - Larson, Melissa

AU - Pigneux, Arnaud

AU - Recher, Christian

AU - Schiller, Gary

AU - Warzocha, Krzysztof

AU - Kantarjian, Hagop

AU - Louie, Arthur C.

AU - Kolitz, Jonathan E.

PY - 2015/1/15

Y1 - 2015/1/15

N2 - 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.

AB - 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.

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KW - Chemotherapy intervention

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KW - Phase II

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