Ibrutinib, Bortezomib and Rituximab-CHOP for the Treatment of Elderly Patients With CD20+ DLBCL, IPI ≥ 2

Summary

The ImbruVeRCHOP-Trials is an Investigator-initiated, single-arm, multi-center, prospective, open phase I/II trial to evaluate the efficacy and feasibility of Ibrutinib and Bortezomib in the therapy of higher-risk DLBCL patients of different molecular subtypes and to correlate outcome with clinical, molecular and imaging-guided response parameters. The protocol includes a safety run-in phase, i.e. the phase I part of the study, to uncover unexpected toxicities that may arise in the context of Ibrutinib and Bortezomib co-administered with the R-CHOP backbone. The safety run-in phase is followed by the phase II part of the trial. About 34 patients will be included. Additional 8-11 German university centers and 1-5 in Austria will participate in this trial. The study treatment includes a pre-phase therapy with Prednisone and 6 cycles of a combined immuno-chemotherapy with the anti-CD20 antibody Rituximab together with 6 cycles of a chemotherapy consisting of Cyclophosphamide, Doxorubicin, Vincristine and Prednisone plus Bortezomib and Ibrutinib followed by two additional 3-week cycles of Rituximab. Secondary endpoints are the predictive power of subtypes (such as GCB/ABC-"cell-of-origin"), markers of minimal residual disease over time and during-the-study-determined markers (e.g. gene signatures) to identify patients who benefit from this treatment addition.

Timeline

Start

2017-03-17

Primary completion

2024-11-12

Completion

2024-11-12

Publications

• Background Denker S, Bittner A, Na IK, Kase J, Frick M, Anagnostopoulos I, Hummel M, Schmitt CA. A Phase I/II first-line study of R-CHOP plus B-cell receptor/NF-kappaB-double-targeting to molecularly assess therapy response. Int J Hematol Oncol. 2019 Dec 19;8(4):IJH20. doi: 10.2217/ijh-2019-0010.
• Vernava I, Schmitt CA. Daratumumab as a novel treatment option in refractory ITP. Blood Cells Mol Dis. 2023 Mar;99:102724. doi: 10.1016/j.bcmd.2023.102724. Epub 2023 Jan 13.

Drugs

Indications