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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Lymphoma
• Intervention / Treatment: Drug: Tocilizumab; Drug: Glofitamab; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone; Drug: Rituximab; Drug: Cyclophosphamide

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: GO43075; Phone Number: 888-662-6728; Email: global-roche-genentech-trials@gene.com

Study Locations

• Denmark
  • Aarhus N, Denmark, 8200
    • Active, not recruiting
    • Aarhus Universitetshospital Skejby; Blodsygdomme
• France
  • Creteil, France, 94010
    • Recruiting
    • Hopital Henri Mondor; Hematologie Clinique
  • Rouen, France, 76038
    • Active, not recruiting
    • Centre Henri Becquerel; Hematologie
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Recruiting
    • Universitair Medisch Centrum Groningen
• Poland
  • Gda?sk, Poland, 80-211
    • Active, not recruiting
    • Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii
  • Lublin, Poland, 20-090
    • Active, not recruiting
    • Centrum Onkologii Ziemi Lubelskiej im. ?w. Jana z Dukli
  • Olsztyn, Poland, 10-228
    • Recruiting
    • Oddzial Kliniczny Hematologii SPZOZ MSWiA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie
  • Pozna?, Poland, 60-569
    • Recruiting
    • Uniwersytecki Szpital Kliniczny w Poznaniu; Oddzial Hematologii i Transplantacji Szpiku
  • Wroc?aw, Poland, 50-367
    • Recruiting
    • Uniwersytecki Szpital Kliniczny; Klinika Hematologii, Nowotworów Krwi i Transplantacji Szpiku
• Spain
  • Barcelona, Spain, 08036
    • Active, not recruiting
    • Hospital Clinic i Provincial de Barcelona; Hematology
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Univ. 12 de Octubre; Servicio de Hematologia
  • Madrid, Spain, 28007
    • Active, not recruiting
    • Hospital General Universitario Gregorio Marañon; Servicio de Hematología
  • Salamanca, Spain, 37007
    • Recruiting
    • Hospital Clinico Universitario de Salamanca;Servicio de Hematologia
• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope Comprehensive Cancer Center
    • Palo Alto, California, United States, 94304
      • Recruiting
      • Stanford Cancer Center
    • Stanford, California, United States, 94305
      • Active, not recruiting
      • Stanford Cancer Institute Inpatient Investigational Pharmacy; Pharmacy
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Active, not recruiting
      • University of Maryland
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Active, not recruiting
      • University of Michigan Health System; UMH Internal Medicine/Hematology-Oncology
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University; Wash Uni. Sch. Of Med
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Recruiting
      • Memorial Sloan Kettering Cancer Center Basking Ridge
    • Middletown, New Jersey, United States, 07748
      • Recruiting
      • Memorial Sloan Kettering - Monmouth
    • Montvale, New Jersey, United States, 07645
      • Recruiting
      • Memorial Sloan Kettering Bergen
  • New York
    • Commack, New York, United States, 11725
      • Recruiting
      • Memorial Sloan-Kettering; Cancer Center
    • Harrison, New York, United States, 10604
      • Recruiting
      • Memorial Sloan Kettering Cancer Center at Westchester
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
    • Uniondale, New York, United States, 11553
      • Recruiting
      • Memorial Sloan Kettering Cancer Center at Nassau
  • Texas
    • Dallas, Texas, United States, 75204
      • Recruiting
      • Baylor University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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: Tocilizumab; Participants will receive tocilizumab as needed to manage cytokine release syndrome (CRS).; Drug: Glofitamab; Participants will receive intravenous (IV) glofitamab as per schedule specified in the treatment arm.; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
End of Treatment Complete Response (EOT CR) Rate	Up to approximately 24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2022
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: July 19, 2021
• First Submitted That Met QC Criteria: July 19, 2021
• First Posted (Actual): July 28, 2021

Study Record Updates

• Last Update Posted (Actual): March 22, 2024
• Last Update Submitted That Met QC Criteria: March 21, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Cyclophosphamide; Rituximab; Prednisone; Doxorubicin; Vincristine
• Other Study ID Numbers: GO43075

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No