Phase i and extension study of clofarabine plus cyclophosphamide in patients with relapsed/refractory acute lymphoblastic leukemia

Stefan Faderl, Kumudha Balakrishnan, Deborah A. Thomas, Farhad Ravandi, Gautam Borthakur, Jan Burger, Alessandra Ferrajoli, Jorge Cortes, Susan O'Brien, Tapan Kadia, Jennie Feliu, William Plunkett, Varsha Gandhi, Hagop M. Kantarjian

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Background Clofarabine is a nucleoside analogue with activity in children with acute lymphoblastic leukemia (ALL). Based on the hypothesis that clofarabine inhibits DNA repair after exposure to DNA-damaging agents, we designed a phase I and extension study to evaluate the combination of clofarabine and cyclophosphamide in adult patients with relapsed/refractory ALL. Methods The continual reassessment method (CRM) was used to define the maximum tolerated dose (MTD). Results Fifty patients with a median age of 30 years (range, 21-72 years) were enrolled, 30 of whom were part of the phase I group. Clofarabine 40 mg/m2 intravenously daily × 3 days and cyclophosphamide 200 mg/m2 intravenously every 12 hours × 3 days were established as the MTDs. Dose limiting toxicity (DLT) included diarrhea, transaminase elevations, and skin rashes. The response rate of the whole study group was 14%, including 10% of patients who achieved complete remission (CR) or CR without platelet recovery (CRp). Three responses occurred in patients with primary refractory disease. Early mortality (< 30 days) was 6%. The median duration of response was 69 days (range, 5-315 days). Median overall survival was about 3 months. Compared with day 1 (cyclophosphamide alone), H2AX phosphorylation was increased on day 2 when clofarabine and cyclophosphamide were administered as a couplet (n = 8). Conclusion The combination of clofarabine plus cyclophosphamide at the doses used in this study in a group of heavily pretreated patients with ALL is only moderately effective. Other doses, alternative schedules, or a more favorable patient population may achieve better results.

Original languageEnglish (US)
Pages (from-to)231-238
Number of pages8
JournalClinical Lymphoma, Myeloma and Leukemia
Issue number3
StatePublished - Jun 2014
Externally publishedYes


  • ALL
  • Clofarabine
  • Salvage chemotherapy

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research


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