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- Title
Phase I and extension study of clofarabine plus cyclophosphamide in patients with relapsed/refractory acute lymphoblastic leukemia.
- Authors
Faderl, Stefan; Balakrishnan, Kumudha; Thomas, Deborah A; Ravandi, Farhad; Borthakur, Gautam; Burger, Jan; Ferrajoli, Alessandra; Cortes, Jorge; O'Brien, Susan; Kadia, Tapan; Feliu, Jennie; Plunkett, William; Gandhi, Varsha; Kantarjian, Hagop M
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>The continual reassessment method (CRM) was used to define the maximum tolerated dose (MTD).<bold>Results: </bold>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/m(2) intravenously daily × 3 days and cyclophosphamide 200 mg/m(2) 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).<bold>Conclusion: </bold>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.
- Publication
Clinical Lymphoma, Myeloma & Leukemia, 2014, Vol 14, Issue 3, p231
- ISSN
2152-2650
- Publication type
journal article
- DOI
10.1016/j.clml.2013.12.001