Clofarabine therapy for the treatment of relapsed or refractory pediatric acute leukemias

Abstract

8504 Background: Despite marked improvement in pediatric leukemia outcome, children with refractory disease or early relapse have a dismal prognosis with the current salvage regimens. Leukemia remains the leading cause of disease-related death in children. New therapeutic options are needed. Clofarabine, a next-generation nucleoside analogue, has shown clinical activity when used as a single agent in heavily pretreated children with relapsed or refractory acute leukemias. Methods: Two Phase 2 multicenter, open-label studies are being conducted with clofarabine in children with refractory or relapsed ALL or AML. Clofarabine is administered at 52 mg/m2/day over 5 consecutive days. Cycles are repeated every 2 to 6 weeks based on response and toxicity. Results: To date 69 patients (40 ALL, 29 AML) have been treated. Median age is 12 years (range 1 to 22 years) and median prior regimens is 3 (range 1 to 6). Forty-one percent had received prior transplant. As determined by independent review, preliminary data indicate overall response rates of 28% in ALL (4 CR, 3 CRp, and 4 PR) and 24% in AML (1 CRp and 6 PR). Median duration of remission is 12 weeks and 6 patients remain in remission with a range of 1 to 65+ weeks. Eight of 18 responding patients (44%) proceeded to bone marrow transplant (BMT). One responding AML patient had previously failed an induction therapy regimen that included cladribine, and 5 other responding patients (2 ALL, 3 AML) had received prior fludarabine as part of a conditioning regimen for BMT. Most drug-related adverse events were transient including fever, nausea/vomiting, headache, skin rash, hand-foot syndrome, elevation in liver enzymes and bilirubin, and infusion-related flushing and anxiety. Pharmacokinetic studies have been performed on the first 28 patients. Conclusions: Clofarabine, a next-generation nucleoside analogue, is active in multiply relapsed or refractory pediatric leukemia patients, including those who have failed prior nucleoside therapies such as cladribine or fludarabine. The toxicity profile is expected and acceptable for this patient population. Remissions are relatively durable, allowing responders to proceed to transplant. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration ILEX Products, Inc., an affiliate of ILEX Oncology ILEX Oncology, Inc.; ILEX Products, Inc., an affiliate of ILEX Oncology ILEX Oncology, Inc. ILEX Oncology, Inc.; ILEX Products, Inc., an affiliate of ILEX Oncology ILEX Oncology, Inc.