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

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04980222
• Other study ID #: GO43075
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: March 22, 2022
• Est. completion date: June 1, 2025

Study information

• Verified date: June 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 46
• Est. completion date: June 1, 2025
• Est. primary completion date: June 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
Denmark	Aarhus Universitetshospital Skejby; Blodsygdomme	Aarhus N
France	Hopital Henri Mondor; Hematologie Clinique	Creteil
France	Centre Henri Becquerel; Hematologie	Rouen
Netherlands	Universitair Medisch Centrum Groningen	Groningen
Poland	Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii	Gda?sk
Poland	Centrum Onkologii Ziemi Lubelskiej im. ?w. Jana z Dukli	Lublin
Poland	Oddzial Kliniczny Hematologii SPZOZ MSWiA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie	Olsztyn
Poland	Uniwersytecki Szpital Kliniczny w Poznaniu; Oddzial Hematologii i Transplantacji Szpiku	Pozna?
Poland	Uniwersytecki Szpital Kliniczny; Klinika Hematologii, Nowotworów Krwi i Transplantacji Szpiku	Wroc?aw
Spain	Hospital Clinic i Provincial de Barcelona; Hematology	Barcelona
Spain	Hospital General Universitario Gregorio Marañon; Servicio de Hematología	Madrid
Spain	Hospital Univ. 12 de Octubre; Servicio de Hematologia	Madrid
Spain	Hospital Clinico Universitario de Salamanca;Servicio de Hematologia	Salamanca
United States	University of Michigan Health System; UMH Internal Medicine/Hematology-Oncology	Ann Arbor	Michigan
United States	University of Maryland	Baltimore	Maryland
United States	Memorial Sloan Kettering Cancer Center Basking Ridge	Basking Ridge	New Jersey
United States	Memorial Sloan-Kettering; Cancer Center	Commack	New York
United States	Baylor University Medical Center	Dallas	Texas
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Memorial Sloan Kettering Cancer Center at Westchester	Harrison	New York
United States	University of Iowa	Iowa City	Iowa
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	New York	New York
United States	Stanford Cancer Center	Palo Alto	California
United States	Washington University; Wash Uni. Sch. Of Med	Saint Louis	Missouri
United States	Stanford Cancer Institute Inpatient Investigational Pharmacy; Pharmacy	Stanford	California
United States	Memorial Sloan Kettering Cancer Center at Nassau	Uniondale	New York

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Denmark,  France,  Netherlands,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	End of Treatment Complete Response (EOT CR) Rate		Up to approximately 24 months
Secondary	Overall Response Rate (ORR) at the EOT		Up to approximately 24 months
Secondary	Progression-free Survival (PFS)		Up to approximately 24 months
Secondary	Overall Survival (OS)		Up to approximately 24 months
Secondary	Percentage of Participants with Adverse Events (AEs)		Up to 90 days after the final dose of study treatment
Secondary	Serum Concentration of Glofitamab		At pre-defined intervals up to approximately 10 months
Secondary	Maximum Concentration (Cmax) of Glofitamab		At pre-defined intervals up to approximately 10 months
Secondary	Total Exposure (AUC) of Glofitamab		At pre-defined intervals up to approximately 10 months