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
- Conditions
- Lymphoma
- Interventions
- Registration Number
- NCT04980222
- Lead Sponsor
- 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 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 46
-
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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Glofitamab + R-CHOP Immunochemotherapy Glofitamab 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) Glofitamab + R-CHOP Immunochemotherapy Cyclophosphamide 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) Glofitamab + R-CHOP Immunochemotherapy Tocilizumab 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) Glofitamab + R-CHOP Immunochemotherapy Vincristine 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) Glofitamab + R-CHOP Immunochemotherapy Doxorubicin 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) Glofitamab + R-CHOP Immunochemotherapy Rituximab 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) Glofitamab + R-CHOP Immunochemotherapy Prednisone 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)
- Primary Outcome Measures
Name Time Method End of Treatment Complete Response (EOT CR) Rate Up to approximately 24 months
- Secondary Outcome Measures
Name Time Method 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 Maximum Concentration (Cmax) of Glofitamab At pre-defined intervals up to approximately 10 months Total Exposure (AUC) of Glofitamab At pre-defined intervals up to approximately 10 months Overall Response Rate (ORR) at the EOT Up to approximately 24 months
Trial Locations
- Locations (25)
Memorial Sloan Kettering Cancer Center at Westchester
🇺🇸Harrison, New York, United States
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States
Stanford Cancer Center
🇺🇸Stanford, California, United States
Stanford Cancer Institute Inpatient Investigational Pharmacy
🇺🇸Stanford, California, United States
University of Iowa
🇺🇸Iowa City, Iowa, United States
Washington University; Wash Uni. Sch. Of Med
🇺🇸Saint Louis, Missouri, United States
Memorial Sloan Kettering Cancer Center Basking Ridge
🇺🇸Basking Ridge, New Jersey, United States
Memorial Sloan Kettering - Monmouth
🇺🇸Middletown, New Jersey, United States
Memorial Sloan Kettering Bergen
🇺🇸Montvale, New Jersey, United States
Memorial Sloan-Kettering; Cancer Center
🇺🇸Commack, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center at Nassau
🇺🇸Uniondale, New York, United States
Baylor University Medical Center
🇺🇸Dallas, Texas, United States
Aarhus Universitetshospital Skejby
🇩🇰Aarhus N, Denmark
Hopital Henri Mondor
🇫🇷Creteil, France
Centre Henri Becquerel
🇫🇷Rouen, France
Universitair Medisch Centrum Groningen
🇳🇱Groningen, Netherlands
Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii
🇵🇱Gda?sk, Poland
Oddzial Kliniczny Hematologii SPZOZ MSWiA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie
🇵🇱Olsztyn, Poland
Uniwersytecki Szpital Kliniczny w Poznaniu
🇵🇱Pozna?, Poland
Uniwersytecki Szpital Kliniczny; Klinika Hematologii, Nowotworów Krwi i Transplantacji Szpiku
🇵🇱Wroc?aw, 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