Phase II trials of clofarabine in pediatric acute leukemia

Abstract

6588 Background: Clofarabine, a next-generation nucleoside analogue, has shown clinical activity when used as a single agent in heavily pretreated patients with relapsed or refractory acute leukemias. The results of two Phase 2 multicenter, open-label studies with clofarabine in children with refractory or relapsed ALL or AML are presented here. Methods: Clofarabine was administered at 52 mg/m2 given by intravenous infusion over 2 hours daily over 5 consecutive days. Cycles were repeated every 2 to 6 weeks based on response and toxicity. Results: 103 patients (61 ALL, 42 AML) have been treated. Patients on the ALL trial had received a median of 3 prior regimens (range 2–6). Thirty percent had received prior transplant. As determined by independent review, preliminary data indicate overall response rates of 30% in ALL (7 CR, 5 CRp, and 6 PR). Median duration of CR/CRp is 29 weeks. On the AML trial, median age was 12 years (range 2–22). Median number of prior regimens was 2 (range 1–5). Forty three percent had received prior transplant. Overall response in AML was 26% (1CRp and 10PR). Most responders on the AML trial proceeded to transplant with an M1 marrow (0–5% blasts) without awaiting peripheral counts recovery. Median duration of remission for AML patients is 12.4 weeks (range 1.1 - 73.4+). Toxicity profile was expected and acceptable for this patient population. Conclusions: Clofarabine is active in heterogenous subtypes of multiply relapsed or refractory pediatric leukemia. Ongoing plans are to evaluate clofarabine combinations in children with ALL and AML. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ilex Products Ilex Products Ilex Products Ilex Products