A multi-center phase i study of clofarabine, etoposide and cyclophosphamide in combination in pediatric patients with refractory or relapsed acute leukemia

N. Hijiya*, P. Gaynon, E. Barry, L. Silverman, B. Thomson, R. Chu, T. Cooper, R. Kadota, M. Rytting, P. Steinherz, V. Shen, S. Jeha, R. Abichandani, W. L. Carroll

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

This Phase I study of clofarabine with etoposide and cyclophosphamide for children with relapsed/refractory acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML) was conducted to determine the maximum tolerated dose (MTD), dose-limiting toxicities and the recommended phase 2 doses (RP2Ds). All three drugs were administered for five consecutive days in induction and four consecutive days in consolidation, for a maximum of eight cycles. A total of 25 patients (20 ALL and 5 AML) were enrolled in five cohorts. An MTD was not reached. The RP2Ds of clofarabine, cyclophosphamide and etoposide were 40, 440 and 100 mg/m 2/day, respectively. Complete remission (CR) was achieved in 10 patients (ALL: nine; AML: one), and CR without platelet recovery in six patients (ALL: two; AML: four) for an overall response rate of 64% (ALL: 55%; AML: 100%). Of the 16 responders, 9 patients proceeded to hematopoietic stem cell transplantation. In conclusion, the combination of clofarabine, etoposide and cyclophosphamide was well tolerated and effective in pediatric patients with relapsed/refractory leukemia. Of note, the phase II portion of the trial was amended after the occurrence of unexpected hepatotoxicity. The ongoing phase II study will evaluate the efficacy and safety of this regimen in ALL patients.

Original languageEnglish (US)
Pages (from-to)2259-2264
Number of pages6
JournalLeukemia
Volume23
Issue number12
DOIs
StatePublished - Dec 2009

Keywords

  • ALL
  • AML
  • children
  • clofarabine
  • relapse

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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