A Phase I/II first-line study of R-CHOP plus B-cell receptor/NF-κB-double-targeting to molecularly assess therapy response

Sophy Denker, Aitomi Bittner, Il-Kang Na, Julia Kase, Mareike Frick, Ioannis Anagnostopoulos, Michael Hummel, Clemens A Schmitt, Sophy Denker, Aitomi Bittner, Il-Kang Na, Julia Kase, Mareike Frick, Ioannis Anagnostopoulos, Michael Hummel, Clemens A Schmitt

Abstract

The ImbruVeRCHOP trial is an investigator-initiated, multicenter, single-arm, open label Phase I/II study for patients 61-80 years of age with newly diagnosed CD20+ diffuse large B-cell lymphoma and a higher risk profile (International Prognostic Index ≥2). Patients receive standard chemotherapy (CHOP) plus immunotherapy (Rituximab), a biological agent (the proteasome inhibitor Bortezomib) and a signaling inhibitor (the Bruton's Tyrosine Kinase-targeting therapeutic Ibrutinib). Using an all-comers approach, but subjecting patients to another lymphoma biopsy acutely under first-cycle immune-chemo drug exposure, ImbruVeRCHOP seeks to identify an unbiased molecular responder signature that marks diffuse large B-cell lymphoma patients at risk and likely to benefit from this regimen as a double, proximal and distal B-cell receptor/NF-κB-co-targeting extension of the current R-CHOP standard of care. EudraCT-Number: 2015-003429-32; ClinicalTrials.gov identifier: NCT03129828.

Keywords: Bortezomib; CHOP; Ibrutinib; Rituximab; biomarkers; chemotherapy; diffuse large B-cell lymphoma; non-Hodgkin lymphoma; novel study design; prediction; targeted therapy.

Conflict of interest statement

Financial & competing interests disclosure CA Schmitt receives honoraria for medical advice from Roche and Janssen-Cilag, and coordinates clinical research (namely the ImbruVeRCHOP trial) partly funded by Janssen-Cilag. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

© 2019 Clemens A Schmitt.

Figures

Figure 1.. Flow chart of the trial…
Figure 1.. Flow chart of the trial sequence and time points of scientific program.
(A) Flow chart showing the course of the study and when material for molecular analysis will be collected. (B) Study logo with double scissors for twofold target in B-cell receptor signaling. (C) Listing of molecular analyses. *Scientific program. CT: Computed tomography; DLBCL: Diffuse large B-cell lymphoma; FISH: Fluorescence in situ hybridization; MRD: Minimal residual disease; PDX: Patient-derived xenograft; PET: Positron emission tomography; sc.: Subcutaneous; TCR-seq: T cell receptor sequencing.

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