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A phase Ib, open-label, dose-escalation trial of the anti-CD37 monoclonal antibody, BI 836826, in combination with gemcitabine and oxaliplatin in patients with relapsed/refractory diffuse large B-cell lymphoma

Background BI 836826 is a chimeric mouse–human monoclonal antibody directed against human CD37, a transmembrane protein expressed on mature B lymphocytes. This open-label, phase I dose-escalation trial (NCT02624492) was conducted to determine the maximum tolerated dose (MTD), safety/tolerability, an...

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Autores principales: Balzarotti, Monica, Magagnoli, Massimo, Canales, Miguel Ángel, Corradini, Paolo, Grande, Carlos, Sancho, Juan-Manuel, Zaja, Francesco, Quinson, Anne-Marie, Belsack, Valérie, Maier, Daniela, Carlo-Stella, Carmelo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279964/
https://www.ncbi.nlm.nih.gov/pubmed/33523334
http://dx.doi.org/10.1007/s10637-020-01054-6
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author Balzarotti, Monica
Magagnoli, Massimo
Canales, Miguel Ángel
Corradini, Paolo
Grande, Carlos
Sancho, Juan-Manuel
Zaja, Francesco
Quinson, Anne-Marie
Belsack, Valérie
Maier, Daniela
Carlo-Stella, Carmelo
author_facet Balzarotti, Monica
Magagnoli, Massimo
Canales, Miguel Ángel
Corradini, Paolo
Grande, Carlos
Sancho, Juan-Manuel
Zaja, Francesco
Quinson, Anne-Marie
Belsack, Valérie
Maier, Daniela
Carlo-Stella, Carmelo
author_sort Balzarotti, Monica
collection PubMed
description Background BI 836826 is a chimeric mouse–human monoclonal antibody directed against human CD37, a transmembrane protein expressed on mature B lymphocytes. This open-label, phase I dose-escalation trial (NCT02624492) was conducted to determine the maximum tolerated dose (MTD), safety/tolerability, and preliminary efficacy of BI 836826 in combination with gemcitabine and oxaliplatin in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Methods Eligible patients received intravenous infusions of BI 836826 on day 8 and gemcitabine 1000 mg/m(2) plus oxaliplatin 100 mg/m(2) on day 1, for up to six 14-day treatment cycles. Dose escalation followed the standard 3 + 3 design. Results Of 21 treated patients, 17 had relapsed/refractory DLBCL and four had follicular lymphoma transformed to DLBCL. BI 836826 dosing started at 25 mg and proceeded through 50 mg and 100 mg. Two dose-limiting toxicities (DLTs) occurred during cycle 1, both grade 4 thrombocytopenia lasting > 7 days, affecting 1/6 evaluable patients (17%) in both the 50 mg and 100 mg cohorts. Due to early termination of the study, the MTD was not determined. The most common adverse events related to BI 836826 treatment were neutropenia (52%), thrombocytopenia (48%), and anemia (48%). Eight patients (38%) experienced BI 836826-related infusion-related reactions (two grade 3). Overall objective response rate was 38%, including two patients (10%) with complete remission and six patients (29%) with partial remission. Conclusions BI 836826 in combination with GemOx was generally well tolerated but did not exceed the MTD at doses up to 100 mg given every 14 days. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10637-020-01054-6.
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spelling pubmed-82799642021-07-20 A phase Ib, open-label, dose-escalation trial of the anti-CD37 monoclonal antibody, BI 836826, in combination with gemcitabine and oxaliplatin in patients with relapsed/refractory diffuse large B-cell lymphoma Balzarotti, Monica Magagnoli, Massimo Canales, Miguel Ángel Corradini, Paolo Grande, Carlos Sancho, Juan-Manuel Zaja, Francesco Quinson, Anne-Marie Belsack, Valérie Maier, Daniela Carlo-Stella, Carmelo Invest New Drugs Phase I Studies Background BI 836826 is a chimeric mouse–human monoclonal antibody directed against human CD37, a transmembrane protein expressed on mature B lymphocytes. This open-label, phase I dose-escalation trial (NCT02624492) was conducted to determine the maximum tolerated dose (MTD), safety/tolerability, and preliminary efficacy of BI 836826 in combination with gemcitabine and oxaliplatin in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Methods Eligible patients received intravenous infusions of BI 836826 on day 8 and gemcitabine 1000 mg/m(2) plus oxaliplatin 100 mg/m(2) on day 1, for up to six 14-day treatment cycles. Dose escalation followed the standard 3 + 3 design. Results Of 21 treated patients, 17 had relapsed/refractory DLBCL and four had follicular lymphoma transformed to DLBCL. BI 836826 dosing started at 25 mg and proceeded through 50 mg and 100 mg. Two dose-limiting toxicities (DLTs) occurred during cycle 1, both grade 4 thrombocytopenia lasting > 7 days, affecting 1/6 evaluable patients (17%) in both the 50 mg and 100 mg cohorts. Due to early termination of the study, the MTD was not determined. The most common adverse events related to BI 836826 treatment were neutropenia (52%), thrombocytopenia (48%), and anemia (48%). Eight patients (38%) experienced BI 836826-related infusion-related reactions (two grade 3). Overall objective response rate was 38%, including two patients (10%) with complete remission and six patients (29%) with partial remission. Conclusions BI 836826 in combination with GemOx was generally well tolerated but did not exceed the MTD at doses up to 100 mg given every 14 days. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10637-020-01054-6. Springer US 2021-02-01 2021 /pmc/articles/PMC8279964/ /pubmed/33523334 http://dx.doi.org/10.1007/s10637-020-01054-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Phase I Studies
Balzarotti, Monica
Magagnoli, Massimo
Canales, Miguel Ángel
Corradini, Paolo
Grande, Carlos
Sancho, Juan-Manuel
Zaja, Francesco
Quinson, Anne-Marie
Belsack, Valérie
Maier, Daniela
Carlo-Stella, Carmelo
A phase Ib, open-label, dose-escalation trial of the anti-CD37 monoclonal antibody, BI 836826, in combination with gemcitabine and oxaliplatin in patients with relapsed/refractory diffuse large B-cell lymphoma
title A phase Ib, open-label, dose-escalation trial of the anti-CD37 monoclonal antibody, BI 836826, in combination with gemcitabine and oxaliplatin in patients with relapsed/refractory diffuse large B-cell lymphoma
title_full A phase Ib, open-label, dose-escalation trial of the anti-CD37 monoclonal antibody, BI 836826, in combination with gemcitabine and oxaliplatin in patients with relapsed/refractory diffuse large B-cell lymphoma
title_fullStr A phase Ib, open-label, dose-escalation trial of the anti-CD37 monoclonal antibody, BI 836826, in combination with gemcitabine and oxaliplatin in patients with relapsed/refractory diffuse large B-cell lymphoma
title_full_unstemmed A phase Ib, open-label, dose-escalation trial of the anti-CD37 monoclonal antibody, BI 836826, in combination with gemcitabine and oxaliplatin in patients with relapsed/refractory diffuse large B-cell lymphoma
title_short A phase Ib, open-label, dose-escalation trial of the anti-CD37 monoclonal antibody, BI 836826, in combination with gemcitabine and oxaliplatin in patients with relapsed/refractory diffuse large B-cell lymphoma
title_sort phase ib, open-label, dose-escalation trial of the anti-cd37 monoclonal antibody, bi 836826, in combination with gemcitabine and oxaliplatin in patients with relapsed/refractory diffuse large b-cell lymphoma
topic Phase I Studies
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279964/
https://www.ncbi.nlm.nih.gov/pubmed/33523334
http://dx.doi.org/10.1007/s10637-020-01054-6
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