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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

Primary Purpose

Lymphoma

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Glofitamab
Tocilizumab
Doxorubicin
Vincristine
Prednisone
Rituximab
Cyclophosphamide
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • City of Hope Comprehensive Cancer CenterRecruiting
  • Stanford Cancer CenterRecruiting
  • Stanford Cancer Institute Inpatient Investigational Pharmacy; Pharmacy
  • University of IowaRecruiting
  • University of MarylandRecruiting
  • University of Michigan Health System; UMH Internal Medicine/Hematology-OncologyRecruiting
  • Washington University; Wash Uni. Sch. Of MedRecruiting
  • Memorial Sloan Kettering Cancer Center Basking RidgeRecruiting
  • Memorial Sloan Kettering - MonmouthRecruiting
  • Memorial Sloan Kettering BergenRecruiting
  • Memorial Sloan-Kettering; Cancer CenterRecruiting
  • Memorial Sloan Kettering Cancer Center at WestchesterRecruiting
  • Memorial Sloan Kettering Cancer CenterRecruiting
  • Memorial Sloan Kettering Cancer Center at NassauRecruiting
  • Baylor University Medical CenterRecruiting
  • Aarhus Universitetshospital Skejby; BlodsygdommeRecruiting
  • Hopital Henri Mondor; Hematologie CliniqueRecruiting
  • Centre Henri Becquerel; HematologieRecruiting
  • Universitair Medisch Centrum Groningen
  • Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i TransplantologiiRecruiting
  • Centrum Onkologii Ziemi Lubelskiej im. ?w. Jana z DukliRecruiting
  • Oddzial Kliniczny Hematologii SPZOZ MSWiA z Warminsko-Mazurskim Centrum Onkologii w OlsztynieRecruiting
  • Uniwersytecki Szpital Kliniczny w Poznaniu; Oddzial Hematologii i Transplantacji SzpikuRecruiting
  • Uniwersytecki Szpital Kliniczny; Klinika Hematologii, Nowotworów Krwi i Transplantacji SzpikuRecruiting
  • Hospital Clinic i Provincial de Barcelona; HematologyRecruiting
  • Hospital General Universitario Gregorio Marañon; Servicio de HematologíaRecruiting
  • Hospital Univ. 12 de Octubre; Servicio de HematologiaRecruiting
  • Hospital Clinico Universitario de Salamanca;Servicio de HematologiaRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Glofitamab + R-CHOP Immunochemotherapy

Arm Description

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)

Outcomes

Primary Outcome Measures

End of Treatment Complete Response (EOT CR) Rate

Secondary Outcome Measures

Overall Response Rate (ORR) at the EOT
Progression-free Survival (PFS)
Overall Survival (OS)
Percentage of Participants with Adverse Events (AEs)
Serum Concentration of Glofitamab
Maximum Concentration (Cmax) of Glofitamab
Total Exposure (AUC) of Glofitamab

Full Information

First Posted
July 19, 2021
Last Updated
October 9, 2023
Sponsor
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT04980222
Brief Title
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
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 22, 2022 (Actual)
Primary Completion Date
June 1, 2025 (Anticipated)
Study Completion Date
June 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Glofitamab + R-CHOP Immunochemotherapy
Arm Type
Experimental
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
Glofitamab
Intervention Description
Participants will receive intravenous (IV) glofitamab as per schedule specified in the treatment arm.
Intervention Type
Drug
Intervention Name(s)
Tocilizumab
Intervention Description
Participants will receive tocilizumab as needed to manage cytokine release syndrome (CRS).
Intervention Type
Drug
Intervention Name(s)
Doxorubicin
Intervention Description
Participants will receive 50 mg/m2 body surface area of doxorubicin IV as per schedule specified in the treatment arm.
Intervention Type
Drug
Intervention Name(s)
Vincristine
Intervention Description
Participants will receive 1.4 mg/m2 body surface area of vincristine IV as per schedule specified in the treatment arm.
Intervention Type
Drug
Intervention Name(s)
Prednisone
Intervention Description
Participants will receive 100 mg of prednisone or prednisolone as per schedule specified in the treatment arm.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
Participants will receive 375 mg/m2 body surface area of rituximab IV as per schedule specified in the treatment arm.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
Participants will receive 750 mg/m2 body surface area of cyclophosphamide IV as per schedule specified in the treatment arm.
Primary Outcome Measure Information:
Title
End of Treatment Complete Response (EOT CR) Rate
Time Frame
Up to approximately 24 months
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR) at the EOT
Time Frame
Up to approximately 24 months
Title
Progression-free Survival (PFS)
Time Frame
Up to approximately 24 months
Title
Overall Survival (OS)
Time Frame
Up to approximately 24 months
Title
Percentage of Participants with Adverse Events (AEs)
Time Frame
Up to 90 days after the final dose of study treatment
Title
Serum Concentration of Glofitamab
Time Frame
At pre-defined intervals up to approximately 10 months
Title
Maximum Concentration (Cmax) of Glofitamab
Time Frame
At pre-defined intervals up to approximately 10 months
Title
Total Exposure (AUC) of Glofitamab
Time Frame
At pre-defined intervals up to approximately 10 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Reference Study ID Number: GO43075
Phone
888-662-6728
Email
global-roche-genentech-trials@gene.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope Comprehensive Cancer Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Recruiting
Facility Name
Stanford Cancer Center
City
Stanford
State/Province
California
ZIP/Postal Code
94305-5820
Country
United States
Individual Site Status
Recruiting
Facility Name
Stanford Cancer Institute Inpatient Investigational Pharmacy; Pharmacy
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
University of Iowa
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Maryland
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Michigan Health System; UMH Internal Medicine/Hematology-Oncology
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Individual Site Status
Recruiting
Facility Name
Washington University; Wash Uni. Sch. Of Med
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Name
Memorial Sloan Kettering Cancer Center Basking Ridge
City
Basking Ridge
State/Province
New Jersey
ZIP/Postal Code
07920
Country
United States
Individual Site Status
Recruiting
Facility Name
Memorial Sloan Kettering - Monmouth
City
Middletown
State/Province
New Jersey
ZIP/Postal Code
07748
Country
United States
Individual Site Status
Recruiting
Facility Name
Memorial Sloan Kettering Bergen
City
Montvale
State/Province
New Jersey
ZIP/Postal Code
07645
Country
United States
Individual Site Status
Recruiting
Facility Name
Memorial Sloan-Kettering; Cancer Center
City
Commack
State/Province
New York
ZIP/Postal Code
11725
Country
United States
Individual Site Status
Recruiting
Facility Name
Memorial Sloan Kettering Cancer Center at Westchester
City
Harrison
State/Province
New York
ZIP/Postal Code
10604
Country
United States
Individual Site Status
Recruiting
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Name
Memorial Sloan Kettering Cancer Center at Nassau
City
Uniondale
State/Province
New York
ZIP/Postal Code
11553
Country
United States
Individual Site Status
Recruiting
Facility Name
Baylor University Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75204
Country
United States
Individual Site Status
Recruiting
Facility Name
Aarhus Universitetshospital Skejby; Blodsygdomme
City
Aarhus N
ZIP/Postal Code
8200
Country
Denmark
Individual Site Status
Recruiting
Facility Name
Hopital Henri Mondor; Hematologie Clinique
City
Creteil
ZIP/Postal Code
94010
Country
France
Individual Site Status
Recruiting
Facility Name
Centre Henri Becquerel; Hematologie
City
Rouen
ZIP/Postal Code
76038
Country
France
Individual Site Status
Recruiting
Facility Name
Universitair Medisch Centrum Groningen
City
Groningen
ZIP/Postal Code
9713 GZ
Country
Netherlands
Individual Site Status
Active, not recruiting
Facility Name
Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii
City
Gda?sk
ZIP/Postal Code
80-211
Country
Poland
Individual Site Status
Recruiting
Facility Name
Centrum Onkologii Ziemi Lubelskiej im. ?w. Jana z Dukli
City
Lublin
ZIP/Postal Code
20-090
Country
Poland
Individual Site Status
Recruiting
Facility Name
Oddzial Kliniczny Hematologii SPZOZ MSWiA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie
City
Olsztyn
ZIP/Postal Code
10-228
Country
Poland
Individual Site Status
Recruiting
Facility Name
Uniwersytecki Szpital Kliniczny w Poznaniu; Oddzial Hematologii i Transplantacji Szpiku
City
Pozna?
ZIP/Postal Code
60-569
Country
Poland
Individual Site Status
Recruiting
Facility Name
Uniwersytecki Szpital Kliniczny; Klinika Hematologii, Nowotworów Krwi i Transplantacji Szpiku
City
Wroc?aw
ZIP/Postal Code
50-367
Country
Poland
Individual Site Status
Recruiting
Facility Name
Hospital Clinic i Provincial de Barcelona; Hematology
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital General Universitario Gregorio Marañon; Servicio de Hematología
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Univ. 12 de Octubre; Servicio de Hematologia
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Clinico Universitario de Salamanca;Servicio de Hematologia
City
Salamanca
ZIP/Postal Code
37007
Country
Spain
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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).

Learn more about this trial

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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