A phase I study of CPX-351 in combination with busulfan and fludarabine conditioning and allogeneic stem cell transplantation in adult patients with refractory acute leukemia. Academic Article uri icon

Overview

MeSH

  • Adult
  • Aged
  • Case-Control Studies
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Recurrence
  • Survival Analysis
  • Transplantation, Homologous

MeSH Major

  • Busulfan
  • Cytarabine
  • Daunorubicin
  • Hematopoietic Stem Cell Transplantation
  • Leukemia, Myeloid, Acute
  • Myeloablative Agonists
  • Transplantation Conditioning
  • Vidarabine

abstract

  • This phase I study evaluated the maximal tolerated dose of CPX-351 when administered sequentially with allogeneic hematopoietic stem cell transplantation (HSCT) in patients with refractory acute leukemia. CPX-351 is a novel liposomal formulation that combines cytosine arabinoside (ara-c) and daunorubicin in a fixed molar ratio of 5:1. Patients in cohorts of 3 were treated with CPX-351 followed by fludarabine and busulfan (Bu/Flu) conditioning at 4-week (schedule A) or 3-week (schedule B) intervals. CPX-351 doses were escalated in 20-U/m(2) increments starting at 60 U/m(2) for 3 doses. Of the 36 patients enrolled, 29 were able to undergo HSCT, and the other 7 (the majority on schedule A) did not proceed to HSCT because of rapid disease progression. The maximal tolerated dose of CPX-351 was not reached at the 120 U/m(2) × 3 dose level. All 29 patients who proceeded to HSCT demonstrated adequate neutrophil and platelet engraftment. The median follow-up on the study for all 36 patients was 205 days (range, 20 to 996 days). The 1-year cumulative incidence of relapse for the 36 patients was 60.1% (95% confidence interval [CI], 43.4% to 77.3%), and that of nonrelapse mortality was 23.8% (95% CI, 10.9% to 47.4%). The 1-year overall survival and leukemia-free survival were 37% (95% CI, 21% to 53%) and 27% (95% CI, 13% to 43%), respectively. Our data suggest that a phase II trial should incorporate CPX-351 120 U/m(2) × 3 dosing on schedule B. Patients with good performance status and those who achieve effective cytoreduction from CPX-351 derived the greatest benefit. Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

publication date

  • July 2013

has subject area

  • Adult
  • Aged
  • Busulfan
  • Case-Control Studies
  • Cytarabine
  • Daunorubicin
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Leukemia, Myeloid, Acute
  • Male
  • Middle Aged
  • Myeloablative Agonists
  • Prognosis
  • Recurrence
  • Survival Analysis
  • Transplantation Conditioning
  • Transplantation, Homologous
  • Vidarabine

Research

keywords

  • Clinical Trial, Phase I
  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1016/j.bbmt.2013.04.013

PubMed ID

  • 23648237

Additional Document Info

start page

  • 1040

end page

  • 1045

volume

  • 19

number

  • 7