Phase I/Phase II study of blinatumomab in pediatric patients with relapsed/refractory acute lymphoblastic leukemia Journal Article


Authors: Von Stackelberg, A.; Locatelli, F.; Zugmaier, G.; Handgretinger, R.; Trippett, T. M.; Rizzari, C.; Bader, P.; O'Brien, M. M.; Brethon, B.; Bhojwani, D.; Schlegel, P. G.; Borkhardt, A.; Rheingold, S. R.; Cooper, T. M.; Zwaan, C. M.; Barnette, P.; Messina, C.; Michel, G.; Dubois, S. G.; Hu, K.; Zhu, M.; Whitlock, J. A.; Gore, L.
Article Title: Phase I/Phase II study of blinatumomab in pediatric patients with relapsed/refractory acute lymphoblastic leukemia
Abstract: Purpose Blinatumomab is a bispecific T-cell engager antibody construct targeting CD19 on B-cell lymphoblasts. Weevaluated the safety, pharmacokinetics, recommended dosage, and potential for efficacy of blinatumomab in children with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Methods This open-label study enrolled children , 18 years old with relapsed/refractory BCP-ALL in a phase I dosage-escalation part and a phase II part, using 6-week treatment cycles. Primary end points were maximum-tolerated dosage (phase I) and complete remission rate within the first two cycles (phase II). Results We treated 49 patients in phase I and 44 patients in phase II. Four patients had dose-limiting toxicities in cycle 1 (phase I). Three experienced grade 4 cytokine-release syndrome (one attributed to grade 5 cardiac failure); one had fatal respiratory failure. The maximum-tolerated dosage was 15 mg/m2d. Blinatumomab pharmacokinetics was linear across dosage levels and consistent among age groups. On the basis of the phase I data, the recommended blinatumomab dosage for children with relapsed/refractory ALL was 5 mg/m2d for the first 7 days, followed by 15 mg/m2d thereafter. Among the 70 patients who received the recommended dosage, 27 (39%; 95% CI, 27% to 51%) achieved complete remission within the first two cycles, 14 (52%) of whom achieved complete minimal residual disease response. The most frequent grade $ 3 adverse events were anemia (36%), thrombocytopenia (21%), and hypokalemia (17%). Three patients (4%) and one patient (1%) had cytokine-release syndrome of grade 3 and 4, respectively. Two patients (3%) interrupted treatment after grade 2 seizures. Conclusion This trial, which to the best of our knowledge was the first such trial in pediatrics, demonstrated antileukemic activity of single-agent blinatumomab with complete minimal residual disease response in children with relapsed/refractory BCP-ALL. Blinatumomab may represent an important new treatment option in this setting, requiring further investigation in curative indications. © 2016 by American Society of Clinical Oncology.
Journal Title: Journal of Clinical Oncology
Volume: 34
Issue: 36
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2016-12-20
Start Page: 4381
End Page: 4389
Language: English
DOI: 10.1200/JCO.2016.67.3301
PROVIDER: scopus
PUBMED: 27998223
DOI/URL:
Notes: Article -- Export Date: 2 February 2017 -- Source: Scopus
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