A Study to Evaluate the Safety and Efficacy of Glofitamab in Combination With Rituximab (R) Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP) in Circulating Tumor (ct)DNA High-Risk Patients With Untreated Diffuse Large B-Cell Lymphoma

NCT ID: NCT04980222

Last Updated: 2025-11-18

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-22
• Study Completion Date: 2026-09-30

Brief Summary

This Phase II, open-label, multicenter study will evaluate the safety, efficacy, and pharmacokinetics of glofitamab in combination with rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in individuals with circulating tumor DNA (ctDNA) high-risk diffuse large B-cell lymphoma (DLBCL), as the first line of treatment.

Conditions

Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Glofitamab + R-CHOP Immunochemotherapy

Participants will receive step-up doses of glofitamab, starting on Day 8 of Cycle 3 (2.5 mg), Day 15 of Cycle 3 (10 mg), then 30 mg glofitamab will be given every three weeks (Q3W) onwards, on Day 8 of Cycles 4-6 and on Day 1 of Cycles 7-10. (cycle length = 21 days)

Participants will receive rituximab, cyclophosphamide, doxorubicin, and vincristine Q3W on Day 1 of Cycles 1-6. Prednisone or prednisolone will be administered daily (QD) on Days 1-5 of Cycles 1-6. (cycle length = 21 days)

Group Type: EXPERIMENTAL

Glofitamab

Intervention Type: DRUG

Participants will receive intravenous (IV) glofitamab as per schedule specified in the treatment arm.

Tocilizumab

Intervention Type: DRUG

Participants will receive tocilizumab as needed to manage cytokine release syndrome (CRS).

Doxorubicin

Intervention Type: DRUG

Participants will receive 50 mg/m2 body surface area of doxorubicin IV as per schedule specified in the treatment arm.

Vincristine

Intervention Type: DRUG

Participants will receive 1.4 mg/m2 body surface area of vincristine IV as per schedule specified in the treatment arm.

Prednisone

Intervention Type: DRUG

Participants will receive 100 mg of prednisone or prednisolone as per schedule specified in the treatment arm.

Rituximab

Intervention Type: DRUG

Participants will receive 375 mg/m2 body surface area of rituximab IV as per schedule specified in the treatment arm.

Cyclophosphamide

Intervention Type: DRUG

Participants will receive 750 mg/m2 body surface area of cyclophosphamide IV as per schedule specified in the treatment arm.

Interventions

Glofitamab

Participants will receive intravenous (IV) glofitamab as per schedule specified in the treatment arm.

Intervention Type: DRUG

Tocilizumab

Participants will receive tocilizumab as needed to manage cytokine release syndrome (CRS).

Intervention Type: DRUG

Doxorubicin

Participants will receive 50 mg/m2 body surface area of doxorubicin IV as per schedule specified in the treatment arm.

Intervention Type: DRUG

Vincristine

Participants will receive 1.4 mg/m2 body surface area of vincristine IV as per schedule specified in the treatment arm.

Intervention Type: DRUG

Prednisone

Participants will receive 100 mg of prednisone or prednisolone as per schedule specified in the treatment arm.

Intervention Type: DRUG

Rituximab

Participants will receive 375 mg/m2 body surface area of rituximab IV as per schedule specified in the treatment arm.

Intervention Type: DRUG

Cyclophosphamide

Participants will receive 750 mg/m2 body surface area of cyclophosphamide IV as per schedule specified in the treatment arm.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Previously untreated patients with CD20-positive DLBCL, including one of the following diagnoses made according to the 2016 World Health Organization (WHO) classification of lymphoid neoplasms

• DLBCL, not otherwise specified, including GCB and ABC/non-GCB types as well as double-expressor lymphoma (coexpression of MYC and BCL2)
• High-grade B-cell lymphoma (HGBCL) with MYC and BCL2 and/or BCL6 translocations
• Patients with de novo transformed follicular lymphoma (patients with discordant bone marrow involvement, i.e., evidence of low-grade histology in bone marrow) may be considered after discussion with the Medical Monitor
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
• International Prognostic Index (IPI): 2-5
• Life expectancy of at least 6 months
• Adequate biomarker blood samples prior to initiation of R-CHOP on Day 1 of Cycle 1 and on Day 1 of Cycle 2 submitted for screening for determination of ctDNA status
• At least one bi-dimensionally fluorodeoxyglucose (FDG)-avid measurable lymphoma lesion on positron emission tomography/computed tomography (PET/CT) scan
• Left ventricular ejection fraction (LVEF) >=50%, as determined on cardiac multiple-gated acquisition (MUGA) scan or cardiac echocardiogram (ECHO)
• Adequate hematopoietic function
• Contraception use

Additional Inclusion Criterion for ctDNA High-Risk Participants:

• Plasma sample evaluated to be ctDNA high risk

Exclusion Criteria

• Current diagnosis of B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classic Hodgkin lymphoma (gray-zone lymphoma), primary mediastinal (thymic) large B-cell lymphoma, T-cell/histiocyte-rich large B-cell lymphoma, Burkitt lymphoma, central nervous system (CNS) lymphoma (primary or secondary involvement), primary effusion DLBCL, and primary cutaneous DLBCL
• Contraindication to any of the individual components of R-CHOP, including prior receipt of anthracyclines, history of severe allergic or anaphylactic reactions to murine monoclonal antibodies, or known sensitivity or allergy to murine products
• Prior treatment for indolent lymphoma
• Prior solid organ or allogeneic stem cell transplant
• Prior therapy for DLBCL and high-grade B-cell lymphoma (HGBCL) with the exception of palliative, short-term treatment with corticosteroids
• Pregnant or breastfeeding, or intending to become pregnant during the study or within 12 months after the final dose of R-CHOP, 3 months after the final dose of tocilizumab (if applicable), or 2 months after the final dose of glofitamab

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Stanford Cancer Center

Stanford, California, United States

University of Iowa

Iowa City, Iowa, United States

Washington University; Wash Uni. Sch. Of Med

St Louis, Missouri, United States

Memorial Sloan Kettering Bergen

Montvale, New Jersey, United States

Memorial Sloan Kettering Cancer Center at Westchester

Harrison, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Baylor University Medical Center

Dallas, Texas, United States

Aarhus Universitetshospital Skejby

Aarhus N, , Denmark

Hopital Henri Mondor

Créteil, , France

Centre Henri Becquerel

Rouen, , France

Universitair Medisch Centrum Groningen

Groningen, , Netherlands

Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii

Gdansk, , Poland

Uniwersytecki Szpital Kliniczny; Klinika Hematologii, Nowotworów Krwi i Transplantacji Szpiku

Wroclaw, , Poland

Hospital Clinic i Provincial de Barcelona

Barcelona, , Spain

Hospital General Universitario Gregorio Marañon

Madrid, , Spain

Hospital Univ. 12 de Octubre; Servicio de Hematologia

Madrid, , Spain

Hospital Clinico Universitario de Salamanca

Salamanca, , Spain

Countries

United States; Denmark; France; Netherlands; Poland; Spain

Other Identifiers

2023-504994-19-00

Identifier Type: CTIS

Identifier Source: secondary_id

GO43075

Identifier Type: -

Identifier Source: org_study_id