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A Study to Evaluate Glofitamab as a Single Agent vs. Investigator's Choice in Participants With Relapsed/Refractory Mantle Cell Lymphoma (GLOBRYTE)

Primary Purpose

Lymphoma

Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Obinutuzumab
Glofitamab
Rituximab
Bendamustine
Lenalidomide
Tocilizumab
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: Life expectancy at least 12 weeks Histologically-confirmed MCL, with documentation of either overexpression of cyclin D1 or the presence of t(11:14) Relapsed (disease progression after the last treatment regimen) or refractory (failure to achieve a partial or complete response from the last treatment regimen) disease At least 1 line of prior systemic therapy including a BTK inhibitor and additional systemic therapy option Confirmed availability of tumor tissue, unless deemed unsafe per investigator assessment At least one bi-dimensionally measurable (defined as at least 1.5 cm) nodal lesion, or one bi-dimensionally measurable (at least 1 cm) extranodal lesion, as measured on CT scan Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 Negative HIV test at screening Adequate hematological function Exclusion Criteria: Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 3 months after the final dose of tocilizumab, 2 months after the final dose of glofitamab, whichever is longer Leukemic, non-nodal MCL History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies (or recombinant antibody-related fusion proteins) or known sensitivity or allergy to murine products Contraindication to obinutuzumab or rituximab, and either bendamustine or lenalidomide Prior treatment with glofitamab or other bispecific antibodies targeting both CD20 and CD3 Prior treatment with CAR-T cell therapy Treatment with systemic therapy or BTK inhibitors, or any investigational agent for the purposes of treating cancer within 2 weeks or 5 half-lives (whichever is shorter) prior to first study treatment Primary or secondary CNS lymphoma at the time of recruitment or history of CNS lymphoma Current or history of CNS disease, such as stroke, epilepisy, CNS vasculitis, or neurodegenerative disease History of other malignancy that could affect compliance with the protocol or interpretation of results Significant or extensive cardiovascular disease Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection at study enrollment or any major episode of infection within 4 weeks prior to the first study treatment Suspected or latent tuberculosis Positive test for hepatitis B virus (HBV) or hepatitis C virus (HCV) Known or suspected chronic active Epstein-Barr viral infection (EBV) Known or suspected history of hemophagocytic lymphohistiocytosis (HLH) Known history of progressive multifocal leukoencephalopathy (PML) Adverse events from prior anti-cancer therapy that have not resolved to Grade 1 or better Administration of a live, attenuated vaccine within 4 weeks before first study treatment administration or anticipation that such a live, attenuated vaccine will be required during the study Prior solid organ transplantation or allogenic stem cell transplant Eligibility for stem cell transplantation (SCT) Active autoimmune disease requiring treatment Prior treatment with systemic immunosuppressive medications within 2 weeks or five half-lives (whichever is shorter) prior to the first dose of study treatment Corticosteroid therapy within 2 weeks prior to first dose of study treatment Recent major surgery (within 4 weeks before the first study treatment) other than for diagnosis Clinically significant history of cirrhotic liver disease

Sites / Locations

  • Beijing Tong Ren Hospital, Capital Medical UniversityRecruiting
  • Fudan University Shanghai Cancer Center; Medical OncologyRecruiting
  • Severance Hospital, Yonsei University Health SystemRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Glofitamab monotherapy

BR or R-Len

Arm Description

Participants will receive two intravenous (IV) obinutuzumab pretreatments prior to receiving IV glofitamab for 12 cycles (cycle length = 21 days).

Participants will receive bendamustine + rituximab for up to 6 cycles (cycle length = 28 days), or rituximab + lenalidomide (cycle length = 28 days) until disease progression.

Outcomes

Primary Outcome Measures

Progression-free survival (PFS)

Secondary Outcome Measures

Complete response (CR) rate
Objective response rate (ORR)
Overall survival (OS)
Time to deterioration in physical functioning/fatigue
Investigator-assessed PFS
Investigator-assessed CR rate
Investigator-assessed ORR
Duration of Complete Response (DOCR)
Duration of Response (DOR)
Proportion of participants reporting each response option for item GP5 from the Functional Assessment of Cancer Therapy - General (FACT-G) subscale
Time to deterioration in lymphoma symptoms
Proportion of participants experiencing a clinically meaningful improvement (3-point or more increase) in lymphoma symptoms as assessed through use of the FACT-Lym LymS
Change from baseline in physical functioning and fatigue at each cycle as assessed by the European Organization for Research and Treatment (EORTC) core Quality of Life Questionnaire (QLQ-C30)
The EORTC QLQ-C30 consists of 30 questions assessing five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, and pain), global health status and quality of life (QoL), and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The functioning and symptoms items are scored on a 4-point scale that ranges from "not at all" to "very much," and the global health status and QoL items are scored on a 7-point scale that ranges from "very poor" to "excellent."
Change from baseline in lymphoma symptoms at each cycle as assessed by the FACT-Lym LymS
Serum concentration of glofitamab
Incidence of anti-drug antibodies (ADAs)

Full Information

First Posted
September 14, 2023
Last Updated
October 12, 2023
Sponsor
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT06084936
Brief Title
A Study to Evaluate Glofitamab as a Single Agent vs. Investigator's Choice in Participants With Relapsed/Refractory Mantle Cell Lymphoma
Acronym
GLOBRYTE
Official Title
A Phase III, Open-Label, Multicenter Randomized Study Evaluating Glofitamab as a Single Agent Versus Investigator's Choice in Patients With Relapsed/Refractory Mantle Cell Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 13, 2023 (Anticipated)
Primary Completion Date
February 2, 2026 (Anticipated)
Study Completion Date
December 31, 2026 (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
Yes

5. Study Description

Brief Summary
The purpose of this study is to evaluate the efficacy of glofitamab monotherapy compared with an investigator's choice of either rituximab plus bendamustine (BR), or lenalidomide with rituximab (R-Len) in patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL).

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 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
182 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Glofitamab monotherapy
Arm Type
Experimental
Arm Description
Participants will receive two intravenous (IV) obinutuzumab pretreatments prior to receiving IV glofitamab for 12 cycles (cycle length = 21 days).
Arm Title
BR or R-Len
Arm Type
Active Comparator
Arm Description
Participants will receive bendamustine + rituximab for up to 6 cycles (cycle length = 28 days), or rituximab + lenalidomide (cycle length = 28 days) until disease progression.
Intervention Type
Drug
Intervention Name(s)
Obinutuzumab
Intervention Description
Participants will receive two 1000 mg pretreatments of intravenous (IV) obinutuzumab from Cycle 1 Day 1
Intervention Type
Drug
Intervention Name(s)
Glofitamab
Intervention Description
Participants will receive IV glofitamab beginning Cycle 1 Day 8 for 12 cycles (cycle length = 21 days).
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
Participants will receive IV rituximab every 28 days for up to 6 cycles (when in combination with bendamustine), or until disease progression (when in combination with lenalidomide).
Intervention Type
Drug
Intervention Name(s)
Bendamustine
Intervention Description
Participants will receive IV bendamustine on Days 1 and 2 Q4W for 6 cycles (cycle length = 28 days).
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Intervention Description
Participants will receive oral lenalidomide once daily on Days 1-21 Q4W until disease progression.
Intervention Type
Drug
Intervention Name(s)
Tocilizumab
Intervention Description
Participants will receive IV tocilizumab as required to manage cytokine release syndrome (CRS) events.
Primary Outcome Measure Information:
Title
Progression-free survival (PFS)
Time Frame
From randomization to the first occurrence of disease progression or death from any cause (up to approximately 24 months)
Secondary Outcome Measure Information:
Title
Complete response (CR) rate
Time Frame
Up to approximately 24 months
Title
Objective response rate (ORR)
Time Frame
Up to approximately 24 months
Title
Overall survival (OS)
Time Frame
From randomization to death from any cause (up to approximately 24 months)
Title
Time to deterioration in physical functioning/fatigue
Time Frame
From randomization to a 10-point decrease in physical functioning/10-point increase in fatigue compared to baseline (up to approximately 24 months)
Title
Investigator-assessed PFS
Time Frame
From randomization to disease progression or death from any cause (up to approximately 24 months)
Title
Investigator-assessed CR rate
Time Frame
Up to approximately 24 months
Title
Investigator-assessed ORR
Time Frame
Up to approximately 24 months
Title
Duration of Complete Response (DOCR)
Time Frame
From the initial occurrence of a documented CR until documented disease progression or death due to any cause, whichever occurs first (up to approximately 24 months)
Title
Duration of Response (DOR)
Time Frame
From the initial occurrence of a documented CR until documented disease progression or death due to any cause, whichever occurs first (up to approximately 24 months)
Title
Proportion of participants reporting each response option for item GP5 from the Functional Assessment of Cancer Therapy - General (FACT-G) subscale
Time Frame
Up to approximately 24 months
Title
Time to deterioration in lymphoma symptoms
Time Frame
From randomization to the first documentation of a 3-point or more decrease in score as assessed by the FACT-Lym lymphoma subscale (LymS) questionnaire (up to approximately 24 months)
Title
Proportion of participants experiencing a clinically meaningful improvement (3-point or more increase) in lymphoma symptoms as assessed through use of the FACT-Lym LymS
Time Frame
Up to approximately 24 months
Title
Change from baseline in physical functioning and fatigue at each cycle as assessed by the European Organization for Research and Treatment (EORTC) core Quality of Life Questionnaire (QLQ-C30)
Description
The EORTC QLQ-C30 consists of 30 questions assessing five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, and pain), global health status and quality of life (QoL), and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The functioning and symptoms items are scored on a 4-point scale that ranges from "not at all" to "very much," and the global health status and QoL items are scored on a 7-point scale that ranges from "very poor" to "excellent."
Time Frame
Up to approximately 24 months
Title
Change from baseline in lymphoma symptoms at each cycle as assessed by the FACT-Lym LymS
Time Frame
Up to approximately 24 months
Title
Serum concentration of glofitamab
Time Frame
Up to approximately 24 months
Title
Incidence of anti-drug antibodies (ADAs)
Time Frame
Up to approximately 24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Life expectancy at least 12 weeks Histologically-confirmed MCL, with documentation of either overexpression of cyclin D1 or the presence of t(11:14) Relapsed (disease progression after the last treatment regimen) or refractory (failure to achieve a partial or complete response from the last treatment regimen) disease At least 1 line of prior systemic therapy including a BTK inhibitor and additional systemic therapy option Confirmed availability of tumor tissue, unless deemed unsafe per investigator assessment At least one bi-dimensionally measurable (defined as at least 1.5 cm) nodal lesion, or one bi-dimensionally measurable (at least 1 cm) extranodal lesion, as measured on CT scan Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 Negative HIV test at screening Adequate hematological function Exclusion Criteria: Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 3 months after the final dose of tocilizumab, 2 months after the final dose of glofitamab, whichever is longer Leukemic, non-nodal MCL History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies (or recombinant antibody-related fusion proteins) or known sensitivity or allergy to murine products Contraindication to obinutuzumab or rituximab, and either bendamustine or lenalidomide Prior treatment with glofitamab or other bispecific antibodies targeting both CD20 and CD3 Prior treatment with CAR-T cell therapy Treatment with systemic therapy or BTK inhibitors, or any investigational agent for the purposes of treating cancer within 2 weeks or 5 half-lives (whichever is shorter) prior to first study treatment Primary or secondary CNS lymphoma at the time of recruitment or history of CNS lymphoma Current or history of CNS disease, such as stroke, epilepisy, CNS vasculitis, or neurodegenerative disease History of other malignancy that could affect compliance with the protocol or interpretation of results Significant or extensive cardiovascular disease Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection at study enrollment or any major episode of infection within 4 weeks prior to the first study treatment Suspected or latent tuberculosis Positive test for hepatitis B virus (HBV) or hepatitis C virus (HCV) Known or suspected chronic active Epstein-Barr viral infection (EBV) Known or suspected history of hemophagocytic lymphohistiocytosis (HLH) Known history of progressive multifocal leukoencephalopathy (PML) Adverse events from prior anti-cancer therapy that have not resolved to Grade 1 or better Administration of a live, attenuated vaccine within 4 weeks before first study treatment administration or anticipation that such a live, attenuated vaccine will be required during the study Prior solid organ transplantation or allogenic stem cell transplant Eligibility for stem cell transplantation (SCT) Active autoimmune disease requiring treatment Prior treatment with systemic immunosuppressive medications within 2 weeks or five half-lives (whichever is shorter) prior to the first dose of study treatment Corticosteroid therapy within 2 weeks prior to first dose of study treatment Recent major surgery (within 4 weeks before the first study treatment) other than for diagnosis Clinically significant history of cirrhotic liver disease
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Reference Study ID Number: GO43878 https://forpatients.roche.com/
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
Beijing Tong Ren Hospital, Capital Medical University
City
Beijing
ZIP/Postal Code
100730
Country
China
Individual Site Status
Recruiting
Facility Name
Fudan University Shanghai Cancer Center; Medical Oncology
City
Shanghai City
ZIP/Postal Code
201315
Country
China
Individual Site Status
Recruiting
Facility Name
Severance Hospital, Yonsei University Health System
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
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 Glofitamab as a Single Agent vs. Investigator's Choice in Participants With Relapsed/Refractory Mantle Cell Lymphoma

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