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

Purpose

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).

Condition

  • Lymphoma

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Glofitamab monotherapy 		Participants will receive two intravenous (IV) obinutuzumab pretreatments prior to receiving IV glofitamab for 12 cycles (cycle length = 21 days).
  • Drug: Obinutuzumab
    Participants will receive two 1000 mg pretreatments of intravenous (IV) obinutuzumab from Cycle 1 Day 1
  • Drug: Glofitamab
    Participants will receive IV glofitamab beginning Cycle 1 Day 8 for 12 cycles (cycle length = 21 days).
  • Drug: Tocilizumab
    Participants will receive IV tocilizumab as required to manage cytokine release syndrome (CRS) events.
Active Comparator
BR or R-Len 		Participants will receive bendamustine + rituximab for up to 6 cycles (cycle length = 28 days), or rituximab + lenalidomide (cycle length = 28 days) until disease progression.
  • Drug: Rituximab
    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).
  • Drug: Bendamustine
    Participants will receive IV bendamustine on Days 1 and 2 Q4W for 6 cycles (cycle length = 28 days).
  • Drug: Lenalidomide
    Participants will receive oral lenalidomide once daily on Days 1-21 Q4W until disease progression.
  • Drug: Tocilizumab
    Participants will receive IV tocilizumab as required to manage cytokine release syndrome (CRS) events.

Recruiting Locations

City of Hope Cancer Center
Duarte 5344147, California 5332921 91010

University of California Los Angeles (UCLA) - Cancer Care - Santa Monica
Santa Monica 5393212, California 5332921 90404-2023

Yale Cancer Center
New Haven 4839366, Connecticut 4831725 06520

Georgetown University
Washington D.C. 4140963, District of Columbia 4138106 20007

University of Miami
Coral Gables 4151871, Florida 4155751 33146

University of Michigan Health System
Ann Arbor 4984247, Michigan 5001836 48109

St. Luke's Hospital
Chesterfield 4381072, Missouri 4398678 63017

Rutgers Cancer Institute of New Jersey
New Brunswick 5101717, New Jersey 5101760 08901

University of Rochester
Rochester 5134086, New York 5128638 14642

Medical University of S. Carolina
Charleston 4574324, South Carolina 4597040 29425

Renovatio Clinical - El Paso
El Paso 5520993, Texas 4736286 79915

Renovatio Clinical
The Woodlands 4736476, Texas 4736286 77380

University of Virginia
Charlottesville 4752031, Virginia 6254928 22906

West Virginia University
Morgantown 4815352, West Virginia 4826850 26506

Auxilio Mutuo Cancer Center
San Juan 4568127, Puerto Rico 00918

More Details

Status
Recruiting
Sponsor
Hoffmann-La Roche

Study Contact

Reference Study ID Number: GO43878 https://forpatients.roche.com/
888-662-6728
global-roche-genentech-trials@gene.com