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

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04980222

Collaborator

(none)

Enrollment

Locations

Arm

38.3

Anticipated Duration (Months)

2.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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

Anticipated 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 :

Mar 22, 2022

Anticipated Primary Completion Date :

Jun 1, 2025

Anticipated Study Completion Date :

Jun 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.

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

End of Treatment Complete Response (EOT CR) Rate [Up to approximately 24 months]

Secondary Outcome Measures

Overall Response Rate (ORR) at the EOT [Up to approximately 24 months]
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010
2	University of Iowa	Iowa City	Iowa	United States	52242
3	Aarhus Universitetshospital Skejby; Blodsygdomme	Aarhus N		Denmark	8200
4	Hopital Henri Mondor; Hematologie Clinique	Creteil		France	94010
5	Centre Henri Becquerel; Hematologie	Rouen		France	76038
6	Universitair Medisch Centrum Groningen	Groningen		Netherlands	9713 GZ
7	Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii	Gdańsk		Poland	80-211
8	Centrum Onkologii Ziemi Lubelskiej im. św. Jana z Dukli	Lublin		Poland	20-090
9	Oddzial Kliniczny Hematologii SPZOZ MSWiA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie	Olsztyn		Poland	10-228
10	Uniwersytecki Szpital Kliniczny; Klinika Hematologii, Nowotworów Krwi i Transplantacji Szpiku	Wrocław		Poland	50-367
11	Hospital Clinic i Provincial de Barcelona; Hematology	Barcelona		Spain	08036
12	Hospital General Universitario Gregorio Marañon; Servicio de Hematología	Madrid		Spain	28007
13	Hospital Univ. 12 de Octubre; Servicio de Hematologia	Madrid		Spain	28041
14	Hospital Clinico Universitario de Salamanca;Servicio de Hematologia	Salamanca		Spain	37007