Skip to main content
eScholarship
Open Access Publications from the University of California

UC Irvine

UC Irvine Previously Published Works bannerUC Irvine

Phase I and Extension Study of Clofarabine Plus Cyclophosphamide in Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia

Abstract

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/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).

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.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
For improved accessibility of PDF content, download the file to your device.
Current View