Open-label bendamustine monotherapy for pediatric patients with relapsed or refractory acute leukemia: efficacy and tolerability.
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.
*Royal Children's Hospital, Brisbane, Qld, Australia †Johns Hopkins University School of Medicine, Baltimore, MD ‡University of Mississippi, Jackson, MS §Cancer Research Institute, Seoul National University College of Medicine ∥The Catholic University of Korea, Seoul, Republic of Korea ¶CHOC Children's, Orange, CA #Pharmaceutical Product Development Inc., Wilmington, NC **The Children's Hospital of Philadelphia, Philadelphia, PA ††CSL Behring, King of Prussia, PA (formerly of Cephalon Inc., which is now a wholly owned subsidiary of Teva Branded Pharmaceutical Products R&D Inc., Frazer, PA) ‡‡Teva Branded Pharmaceutical Products R&D Inc., Frazer, PA §§CSL Behring, King of Prussia, PA (formerly of Teva Branded Pharmaceutical Products R&D Inc., Frazer, PA) ∥∥Southwestern Medical Center, University of Texas, Dallas, TX.
Chris
C
Fraser
Patrick
P
Brown
Gail
G
Megason
Hyo Seop
HS
Ahn
Bin
B
Cho
Ivan
I
Kirov
Lawrence
L
Frankel
Richard
R
Aplenc
Debra
D
Bensen-Kennedy
Mihaela
M
Munteanu
Jennifer
J
Weaver
Paul
P
Harker-Murray
D000293:Adolescent; D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000009:adverse effects; D000069461:Bendamustine Hydrochloride; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D009588:Nitrogen Mustard Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology / Q000517:prevention & control*; D012008:Recurrence
D018906:Antineoplastic Agents, Alkylating; D009588:Nitrogen Mustard Compounds; D000069461:Bendamustine Hydrochloride