TY - JOUR
T1 - Open-label bendamustine monotherapy for pediatric patients with relapsed or refractory acute leukemia
T2 - Efficacy and tolerability
AU - Fraser, Chris
AU - Brown, Patrick
AU - Megason, Gail
AU - Ahn, Hyo Seop
AU - Cho, Bin
AU - Kirov, Ivan
AU - Frankel, Lawrence
AU - Aplenc, Richard
AU - Bensen-Kennedy, Debra
AU - Munteanu, Mihaela
AU - Weaver, Jennifer
AU - Harker-Murray, Paul
PY - 2014/5
Y1 - 2014/5
N2 - 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/m2. In phase II, 32 patients received bendamustine 120 mg/m2. Two patients with ALL (bendamustine 90 mg/m2) experienced complete response (CR). Among patients who received bendamustine 120 mg/m2, 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.
AB - 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/m2. In phase II, 32 patients received bendamustine 120 mg/m2. Two patients with ALL (bendamustine 90 mg/m2) experienced complete response (CR). Among patients who received bendamustine 120 mg/m2, 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.
KW - acute lymphoblastic leukemia
KW - acute myeloid leukemia
KW - bendamustine
KW - dose-ranging study
KW - overall response rate
UR - http://www.scopus.com/inward/record.url?scp=84899920098&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84899920098&partnerID=8YFLogxK
U2 - 10.1097/MPH.0000000000000021
DO - 10.1097/MPH.0000000000000021
M3 - Article
C2 - 24072240
AN - SCOPUS:84899920098
SN - 1077-4114
VL - 36
SP - e212-e218
JO - Journal of Pediatric Hematology/Oncology
JF - Journal of Pediatric Hematology/Oncology
IS - 4
ER -