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

Jeffrey E. Lancet, Jorge E. Cortes, Donna E. Hogge, Martin S. Tallman, Tibor J. Kovacsovics, Lloyd E. Damon, Rami Komrokji, Scott R. Solomon, Jonathan E. Kolitz, Maureen Cooper, Andrew M Yeager, Arthur C. Louie, Eric J. Feldman

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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 andOS were not statistically significant.Aplanned analysis of the secondaryAMLsubgroup 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 50.46, 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.

Original languageEnglish (US)
Pages (from-to)3239-3246
Number of pages8
JournalBlood
Volume123
Issue number21
DOIs
StatePublished - May 22 2014

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Daunorubicin
Cytarabine
Acute Myeloid Leukemia
Pharmaceutical Preparations
Infection
Disease-Free Survival
Leukemia
Safety
Survival
Mortality
Therapeutics

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Lancet, J. E., Cortes, J. E., Hogge, D. E., Tallman, M. S., Kovacsovics, T. J., Damon, L. E., ... Feldman, E. J. (2014). Phase 2 trial of CPX-351, a fixed 5: 1 molar ratio of cytarabine/ daunorubicin, vs cytarabine/daunorubicin in older adults with untreated AML. Blood, 123(21), 3239-3246. https://doi.org/10.1182/blood-2013-12-540971

Phase 2 trial of CPX-351, a fixed 5 : 1 molar ratio of cytarabine/ daunorubicin, vs cytarabine/daunorubicin in older adults with untreated AML. / Lancet, Jeffrey E.; Cortes, Jorge E.; Hogge, Donna E.; Tallman, Martin S.; Kovacsovics, Tibor J.; Damon, Lloyd E.; Komrokji, Rami; Solomon, Scott R.; Kolitz, Jonathan E.; Cooper, Maureen; Yeager, Andrew M; Louie, Arthur C.; Feldman, Eric J.

In: Blood, Vol. 123, No. 21, 22.05.2014, p. 3239-3246.

Research output: Contribution to journalArticle

Lancet, JE, Cortes, JE, Hogge, DE, Tallman, MS, Kovacsovics, TJ, Damon, LE, Komrokji, R, Solomon, SR, Kolitz, JE, Cooper, M, Yeager, AM, Louie, AC & Feldman, EJ 2014, 'Phase 2 trial of CPX-351, a fixed 5: 1 molar ratio of cytarabine/ daunorubicin, vs cytarabine/daunorubicin in older adults with untreated AML', Blood, vol. 123, no. 21, pp. 3239-3246. https://doi.org/10.1182/blood-2013-12-540971
Lancet, Jeffrey E. ; Cortes, Jorge E. ; Hogge, Donna E. ; Tallman, Martin S. ; Kovacsovics, Tibor J. ; Damon, Lloyd E. ; Komrokji, Rami ; Solomon, Scott R. ; Kolitz, Jonathan E. ; Cooper, Maureen ; Yeager, Andrew M ; Louie, Arthur C. ; Feldman, Eric J. / Phase 2 trial of CPX-351, a fixed 5 : 1 molar ratio of cytarabine/ daunorubicin, vs cytarabine/daunorubicin in older adults with untreated AML. In: Blood. 2014 ; Vol. 123, No. 21. pp. 3239-3246.
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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 andOS were not statistically significant.Aplanned analysis of the secondaryAMLsubgroup 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 50.46, 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.",
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