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

Chris Fraser, Patrick A Brown, Gail Megason, Hyo Seop Ahn, Bin Cho, Ivan Kirov, Lawrence Frankel, Richard Aplenc, Debra Bensen-Kennedy, Mihaela Munteanu, Jennifer Weaver, Paul Harker-Murray

Research output: Contribution to journalArticle

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/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.

Original languageEnglish (US)
JournalJournal of Pediatric Hematology/Oncology
Volume36
Issue number4
DOIs
StatePublished - 2014

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Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Pediatrics
Acute Myeloid Leukemia
Bendamustine Hydrochloride
Neutropenia
Thrombocytopenia
Nausea
Vomiting
Anemia
Diarrhea
Fever
Blood Platelets
Pharmacokinetics

Keywords

  • acute lymphoblastic leukemia
  • acute myeloid leukemia
  • bendamustine
  • dose-ranging study
  • overall response rate

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Oncology
  • Hematology

Cite this

Open-label bendamustine monotherapy for pediatric patients with relapsed or refractory acute leukemia : Efficacy and tolerability. / Fraser, Chris; Brown, Patrick A; Megason, Gail; Ahn, Hyo Seop; Cho, Bin; Kirov, Ivan; Frankel, Lawrence; Aplenc, Richard; Bensen-Kennedy, Debra; Munteanu, Mihaela; Weaver, Jennifer; Harker-Murray, Paul.

In: Journal of Pediatric Hematology/Oncology, Vol. 36, No. 4, 2014.

Research output: Contribution to journalArticle

Fraser, C, Brown, PA, Megason, G, Ahn, HS, Cho, B, Kirov, I, Frankel, L, Aplenc, R, Bensen-Kennedy, D, Munteanu, M, Weaver, J & Harker-Murray, P 2014, 'Open-label bendamustine monotherapy for pediatric patients with relapsed or refractory acute leukemia: Efficacy and tolerability', Journal of Pediatric Hematology/Oncology, vol. 36, no. 4. https://doi.org/10.1097/MPH.0000000000000021
Fraser, Chris ; Brown, Patrick A ; Megason, Gail ; Ahn, Hyo Seop ; Cho, Bin ; Kirov, Ivan ; Frankel, Lawrence ; Aplenc, Richard ; Bensen-Kennedy, Debra ; Munteanu, Mihaela ; Weaver, Jennifer ; Harker-Murray, Paul. / Open-label bendamustine monotherapy for pediatric patients with relapsed or refractory acute leukemia : Efficacy and tolerability. In: Journal of Pediatric Hematology/Oncology. 2014 ; Vol. 36, No. 4.
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