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


Authors: Hijiya, N.; Gaynon, P.; Barry, E.; Silverman, L.; Thomson, B.; Chu, R.; Cooper, T.; Kadota, R.; Rytting, M.; Steinherz, P.; Shen, V.; Jeha, S.; Abichandani, R.; Carroll, W. L.
Article Title: A multi-center phase I study of clofarabine, etoposide and cyclophosphamide in combination in pediatric patients with refractory or relapsed acute leukemia
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<sup>2</sup>/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.Leukemia advance online publication, 10 September 2009; doi:10.1038/leu.2009.185.
Journal Title: Leukemia
Volume: 23
ISSN: 0887-6924
Publisher: Nature Publishing Group  
Date Published: 2009-09-10
Start Page: 2259
End Page: 2264
Language: English
DOI: 10.1038/leu.2009.185
PROVIDER: scopus
DOI/URL:
Notes: --- - "Export Date: 30 November 2010" - Article in Press - "CODEN: LEUKE" - "Source: Scopus"
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  1. Peter G Steinherz
    221 Steinherz