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

doi:10.2217/ijh-2019-0010

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

Int J Hematol Oncol. 2019 Dec 19;8(4):IJH20. doi: 10.2217/ijh-2019-0010.

Authors

Sophy Denker¹, Aitomi Bittner¹, Il-Kang Na^{1

2

3

4}, Julia Kase¹, Mareike Frick¹, Ioannis Anagnostopoulos⁵, Michael Hummel^{5

6}, Clemens A Schmitt^{1

6

7

8}

Affiliations

¹ Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, & Berlin Institute of Health; Medical Department of Hematology, Oncology & Tumor Immunology, Virchow Campus & Molekulares Krebsforschungszentrum, Berlin, Germany.
² Experimental & Clinical Research Centre, Berlin, Germany.
³ Berlin Institute of Health, Berlin, Germany.
⁴ Berlin Institute of Health Center for Regenerative Therapies, Berlin, Germany.
⁵ Institute for Pathology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
⁶ German Cancer Consortium (DKTK) & German Cancer Research Centre (DKFZ), Heidelberg, Germany.
⁷ Kepler Universitätsklinikum, Hematology & Oncology, Johannes Kepler University, Linz, Austria.
⁸ Max-Delbrück-Centre for Molecular Medicine in the Helmholtz Association, Berlin, Germany.

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.

Publication types

Clinical Trial Protocol

Associated data

ClinicalTrials.gov/NCT03129828