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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

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

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

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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


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.




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 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04980222


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

Locations
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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
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Study Director: Clinical Trials Hoffmann-La Roche
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT04980222    
Other Study ID Numbers: GO43075
First Posted: July 28, 2021    Key Record Dates
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).

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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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