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

• ClinicalTrials.gov Identifier: NCT04980222
• Recruitment Status: Recruiting
• First Posted: July 28, 2021
• Last Update Posted: July 7, 2022
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

Brief Summary:

This Phase II, open-label, multicenter study will evaluate the safety, efficacy, and pharmacokinetics of glofitamab in combination with Rituximab, 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.

Condition or disease	Intervention/treatment	Phase
Lymphoma	Drug: Glofitamab; Drug: Tocilizumab; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone; Drug: Rituximab; Drug: Cyclophosphamide	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study Evaluating 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
• Actual Study Start Date: March 22, 2022
• Estimated Primary Completion Date: June 1, 2025
• Estimated Study Completion Date: June 1, 2025

Arms and Interventions

Arm

Intervention/treatment

Experimental: 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)

Drug: Glofitamab; Participants will receive intravenous (IV) glofitamab as per schedule specified in the treatment arm.; Drug: Tocilizumab; Participants will receive tocilizumab as needed to manage cytokine release syndrome (CRS).; Drug: Doxorubicin; Participants will receive 50 mg/m2 body surface area of doxorubicin IV as per schedule specified in the treatment arm.; Drug: Vincristine; Participants will receive 1.4 mg/m2 body surface area of vincristine IV as per schedule specified in the treatment arm.; Drug: Prednisone; Participants will receive 100 mg of prednisone or prednisolone as per schedule specified in the treatment arm.; Drug: Rituximab; Participants will receive 375 mg/m2 body surface area of rituximab IV as per schedule specified in the treatment arm.; Drug: Cyclophosphamide; Participants will receive 750 mg/m2 body surface area of cyclophosphamide IV as per schedule specified in the treatment arm.

Outcome Measures

Primary Outcome Measures :

1. End of Treatment Complete Response (EOT CR) Rate [ Time Frame: Up to approximately 24 months ]

Secondary Outcome Measures :

1. Overall Response Rate (ORR) at the EOT [ Time Frame: Up to approximately 24 months ]
2. Progression-free Survival (PFS) [ Time Frame: Up to approximately 24 months ]
3. Overall Survival (OS) [ Time Frame: Up to approximately 24 months ]
4. Percentage of Participants with Adverse Events (AEs) [ Time Frame: Up to 90 days after the final dose of study treatment ]
5. Serum Concentration of Glofitamab [ Time Frame: At pre-defined intervals up to approximately 10 months ]
6. Maximum Concentration (Cmax) of Glofitamab [ Time Frame: At pre-defined intervals up to approximately 10 months ]
7. Total Exposure (AUC) of Glofitamab [ Time Frame: At pre-defined intervals up to approximately 10 months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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, 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

Contacts and Locations

Contacts

Contact: Reference Study ID Number: GO43075; 888-662-6728; global-roche-genentech-trials@gene.com

Locations

United States, California

City of Hope Comprehensive Cancer Center; Recruiting

Duarte, California, United States, 91010

Denmark

Aarhus Universitetshospital Skejby; Blodsygdomme; Recruiting

Aarhus N, Denmark, 8200

France

Hopital Henri Mondor; Hematologie Clinique; Recruiting

Creteil, France, 94010

Centre Henri Becquerel; Hematologie; Recruiting

Rouen, France, 76038

Poland

Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii; Recruiting

Gdańsk, Poland, 80-211

Centrum Onkologii Ziemi Lubelskiej im. św. Jana z Dukli; Recruiting

Lublin, Poland, 20-090

Oddzial Kliniczny Hematologii SPZOZ MSWiA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie; Recruiting

Olsztyn, Poland, 10-228

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

Wrocław, Poland, 50-367

Spain

Hospital Clinic i Provincial de Barcelona; Hematology; Recruiting

Barcelona, Spain, 08036

Hospital General Universitario Gregorio Marañon; Servicio de Hematología; Active, not recruiting

Madrid, Spain, 28007

Hospital Univ. 12 de Octubre; Servicio de Hematologia; Recruiting

Madrid, Spain, 28041

Hospital Clinico Universitario de Salamanca;Servicio de Hematologia; Recruiting

Salamanca, Spain, 37007

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

More Information

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT04980222
• Other Study ID Numbers: GO43075
• First Posted: July 28, 2021
• Last Update Posted: July 7, 2022
• Last Verified: July 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Lymphoma; Lymphoma, Large B-Cell, Diffuse; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Prednisone; Cyclophosphamide; Rituximab; Doxorubicin; Vincristine; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Myeloablative Agonists; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Anti-Inflammatory Agents