Open-label bendamustine monotherapy for pediatric patients with relapsed or refractory acute leukemia: efficacy and tolerability

Abstract

This open-label, single-arm, phase I/II, dose-escalation study was designed to determine the recommended phase II dose (RP2D), pharmacokinetics, tolerability, and efficacy of bendamustine in pediatric patients (age ranging from 1 to 20 y) with histologically proven relapsed/refractory acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML). Patients (27 with ALL, 16 with AML) received intravenous bendamustine on days 1 and 2 of each treatment cycle. Phase I involved planned dose escalation of bendamustine to establish the RP2D for phase II. Objectives included overall response rate, duration of response, and tolerability. Eleven patients were treated in phase I, and the RP2D was 120 mg/m. In phase II, 32 patients received bendamustine 120 mg/m. Two patients with ALL (bendamustine 90 mg/m) experienced complete response (CR). Among patients who received bendamustine 120 mg/m, 2 experienced partial response (PR); 7 had stable disease. The overall response rate (CR+CR without platelet recovery [CRp]) was 4.7% and biological activity rate (CR+CRp+PR) was 9.3%. No AML patients responded. The most common adverse events were anemia, neutropenia, thrombocytopenia, pyrexia, nausea, vomiting, and diarrhea. Bendamustine monotherapy has acceptable tolerability in heavily pretreated children with relapsed/refractory ALL or AML and appears to have some activity in ALL, warranting further studies in combination trials.

Conflict of interest statement

L.F. is employed by PPD-PharmacoVigilance (contractual relationship with Teva Branded Pharmaceutical Products R&D Inc.). D.B.K., M.M., and J.W. were employed by Teva Branded Pharmaceutical Products R&D Inc. at the time the study was conducted. The remaining authors declare no conflict of interest.

Figures

FIGURE 1

Treatment and evaluation plan. *All subsequent cycles require clinical determination of patient benefit. †Count recovery for induction defined as neutrophil count ≥1.0×109/L and platelet count ≥100×109/L. ‡Disease evaluation may include peripheral laboratory testing and/or bone marrow evaluation at the discretion of the treating physician. Count recovery for subsequent cycles defined as platelet count not requiring transfusion and neutrophil count ≥500. §Clinical discretion for additional cycles of therapy is required based on patient’s clinical need; maximum of 35 days for recovery, minimum neutrophil count is 500, and platelet count may be supported with transfusion. CR indicates complete response; CRp, complete response without platelet recovery; PR, partial response; SD, stable disease.

FIGURE 2

Patient disposition.