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
Glofitamab: Participants will receive intravenous (IV) glofitamab as per schedule specified in the treatment arm.
Tocilizumab: Participants will receive tocilizumab as needed to manage cytokine release syndrome (CRS).
Doxorubicin: Participants will receive 50 mg/m2 body surface area of doxorubicin IV as per schedule specified in the treatment arm.
Vincristine: Participants will receive 1.4 mg/m2 body surface area of vincristine IV as per schedule specified in the treatment arm.
Prednisone: Participants will receive 100 mg of prednisone or prednisolone as per schedule specified in the treatment arm.
Rituximab: Participants will receive 375 mg/m2 body surface area of rituximab IV as per schedule specified in the treatment arm.
Cyclophosphamide: Participants will receive 750 mg/m2 body surface area of cyclophosphamide IV as per schedule specified in the treatment arm.
Study 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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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
Primary outcome measure(s)
End of Treatment Complete Response (EOT CR) Rate — Up to approximately 24 months
Trial sites (20)
Facility
City
Region
Status
City of Hope Comprehensive Cancer Center
Duarte
California
Stanford Cancer Center
Stanford
California
Stanford Cancer Institute Inpatient Investigational Pharmacy
Stanford
California
University of Iowa
Iowa City
Iowa
University of Michigan Health System
Ann Arbor
Michigan
Washington University; Wash Uni. Sch. Of Med
St Louis
Missouri
Memorial Sloan Kettering Bergen
Montvale
New Jersey
Memorial Sloan Kettering Cancer Center at Westchester
East White Plains
New York
Memorial Sloan Kettering Cancer Center
New York
New York
Baylor University Medical Center
Dallas
Texas
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
BARCELONA
Hospital General Universitario Gregorio Marañon
Madrid
Madrid
Hospital Univ. 12 de Octubre; Servicio de Hematologia
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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