Efficacy of CPX-351, (cytarabine: DAunorubicin) liposome injection, against acute lymphoblastic leukemia (ALL) xenograft models of the Pediatric Preclinical Testing Program

Hernan Carol, Mannie M.Y. Fan, Troy O. Harasym, Ingrid Boehm, Lawrence D. Mayer, Peter Houghton, Malcolm A. Smith, Richard B. Lock

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Background: CPX-351, a liposomal formulation of cytarabine and daunorubicin co-encapsulated at an optimized synergistic 5:1 molar ratio, has demonstrated improved clinical outcomes over conventional cytarabine/daunorubicin treatment in a randomized phase 2 trial in patients with AML as well as superior efficacy against preclinical leukemia models when compared to the free drugs in combination. Procedures: Given the promising phase 2 data, limited toxicities observed, and the known clinical activities of cytarabine/daunorubicin, we assessed the efficacy of CPX-351 against a panel of childhood ALL xenograft models. Plasma pharmacokinetics of cytarabine and daunorubicin following CPX-351 treatment were determined by HPLC in order to correlate efficacy with drug exposure. Results: CPX-351, at a dose of 5units/kg (corresponding to 5mg/kg cytarabine and 2.2mg/kg daunorubicin), was highly efficacious against all xenografts tested, inducing complete responses in four B-lineage xenografts and partial response in one T-lineage xenograft. These therapeutic responses were achieved with CPX-351 doses that provided drug exposures (based on Cmax and AUC) comparable to those observed in patients with AML. Conclusions: These results suggest that CPX-351 may be a promising chemotherapeutic to be utilized in the treatment of ALL and support its testing in pediatric patients with leukemia.

Original languageEnglish (US)
Pages (from-to)65-71
Number of pages7
JournalPediatric Blood and Cancer
Volume62
Issue number1
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

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Keywords

  • Acute leukemia
  • CPX-351
  • Efficacy
  • Pharmacokinetics
  • Synergy

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

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