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

NCT04980222 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: GO430752023-504994-19-00
• Study Type: interventional
• Target: 46
• Locations: 6 countries
• Sites: 18

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

Outcome Measures

Primary Outcomes (1)

• End of Treatment Complete Response (EOT CR) Rate

  Up to approximately 24 months

Secondary Outcomes (7)

• Overall Response Rate (ORR) at the EOT

  Up to approximately 24 months

• Progression-free Survival (PFS)

  Up to approximately 24 months

• Overall Survival (OS)

  Up to approximately 24 months

• Percentage of Participants with Adverse Events (AEs)

  Up to 90 days after the final dose of study treatment

• Serum Concentration of Glofitamab

  At pre-defined intervals up to approximately 10 months

Study Arms (1)

Glofitamab + R-CHOP Immunochemotherapy

EXPERIMENTAL

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)

Drug: Glofitamab; Drug: Tocilizumab; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone; Drug: Rituximab; Drug: Cyclophosphamide

Interventions

Tocilizumab DRUG

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

Glofitamab + R-CHOP Immunochemotherapy

Doxorubicin DRUG

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

Glofitamab + R-CHOP Immunochemotherapy

Vincristine DRUG

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

Glofitamab + R-CHOP Immunochemotherapy

Glofitamab DRUG

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

Glofitamab + R-CHOP Immunochemotherapy

Prednisone DRUG

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

Glofitamab + R-CHOP Immunochemotherapy

Rituximab DRUG

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

Glofitamab + R-CHOP Immunochemotherapy

Cyclophosphamide DRUG

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

Glofitamab + R-CHOP Immunochemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Plasma sample evaluated to be ctDNA high risk

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (18)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

Stanford Cancer Center

Stanford, California, 94305-5820, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Washington University; Wash Uni. Sch. Of Med

St Louis, Missouri, 63110, United States

Location

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Cancer Center at Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Baylor University Medical Center

Dallas, Texas, 75204, United States

Location

Aarhus Universitetshospital Skejby

Aarhus N, 8200, Denmark

Location

Hopital Henri Mondor

Créteil, 94010, France

Location

Centre Henri Becquerel

Rouen, 76038, France

Location

Universitair Medisch Centrum Groningen

Groningen, 9713 GZ, Netherlands

Location

Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii

Gdansk, 80-211, Poland

Location

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

Wroclaw, 50-367, Poland

Location

Hospital Clinic i Provincial de Barcelona

Barcelona, 08036, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

Location

Hospital Univ. 12 de Octubre; Servicio de Hematologia

Madrid, 28041, Spain

Location

Hospital Clinico Universitario de Salamanca

Salamanca, 37007, Spain

Location

MeSH Terms

Conditions

Lymphoma

Interventions

glofitamab; tocilizumab; Doxorubicin; Vincristine; Prednisone; Rituximab; Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2021
• First Posted: July 28, 2021
• Study Start: March 22, 2022
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: February 17, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

FR (2); US (8); PL (2); DK (1); ES (4); NL (1)