Obinutuzumab: Participants will receive two 1000 mg pretreatments of intravenous (IV) obinutuzumab from Cycle 1 Day 1
Glofitamab: Participants will receive IV glofitamab beginning Cycle 1 Day 8 for 12 cycles (cycle length = 21 days).
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).
Bendamustine: Participants will receive IV bendamustine on Days 1 and 2 Q4W for 6 cycles (cycle length = 28 days).
Lenalidomide: Participants will receive oral lenalidomide once daily on Days 1-21 Q4W until disease progression.
Tocilizumab: Participants will receive IV tocilizumab as required to manage cytokine release syndrome (CRS) events.
Study 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).
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
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) within 12 months of study entry
* 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
Primary outcome measure(s)
Progression-free survival (PFS) — From randomization to the first occurrence of disease progression or death from any cause (up to approximately 24 months)
Trial sites (82)
Facility
City
Region
Status
Alta Bates Summit Medical Center
Berkeley
California
Withdrawn
City of Hope Cancer Center
Duarte
California
Recruiting
Valkyrie Clinical Trials
Los Angeles
California
Recruiting
University of California Los Angeles (UCLA) - Cancer Care - Santa Monica
Santa Monica
California
Recruiting
Yale Cancer Center
New Haven
Connecticut
Recruiting
Georgetown University
Washington D.C.
District of Columbia
Recruiting
University of Miami
Coral Gables
Florida
Recruiting
Moffitt Cancer Center
Tampa
Florida
Recruiting
Indiana University
Indianapolis
Indiana
Withdrawn
University of Iowa
Iowa City
Iowa
Recruiting
University of Iowa Health Care
Waukee
Iowa
Recruiting
University of Michigan Health System
Ann Arbor
Michigan
Recruiting
St. Luke's Hospital
Chesterfield
Missouri
Recruiting
Renown Regional Medical Center
Reno
Nevada
Recruiting
Rutgers Cancer Institute of New Jersey
New Brunswick
New Jersey
Recruiting
Hematology Oncology Associates of Central New York
East Syracuse
New York
Recruiting
University of Rochester
Rochester
New York
Recruiting
Stony Brook University Hospital Cancer Center
Stony Brook
New York
Recruiting
Medical University of S. Carolina
Charleston
South Carolina
Withdrawn
Avera Cancer Institute
Sioux Falls
South Dakota
Withdrawn
Renovatio Clinical - El Paso
El Paso
Texas
Recruiting
Renovatio Clinical
The Woodlands
Texas
Recruiting
University of Virginia
Charlottesville
Virginia
Recruiting
West Virginia University
Morgantown
West Virginia
Recruiting
Calvary Mater Newcastle
Waratah
New South Wales
Recruiting
Royal Adelaide Hospital
Adelaide
South Australia
Recruiting
Epworth Hospital
Richmond
Victoria
Recruiting
Hospital Sao Rafael - HSR
Salvador
Estado de Bahia
Withdrawn
Ictrials Pesquisa e Desenvolvimento
Curitiba
Paraná
Recruiting
Hospital Mae de Deus
Porto Alegre
Rio Grande do Sul
Recruiting
Hospital Paulistano
São Paulo
São Paulo
Recruiting
Hospital Alemao Oswaldo Cruz
São Paulo
São Paulo
Recruiting
Hospital A. C. Camargo
São Paulo
São Paulo
Recruiting
Instituto D'Or Pesquisa e Ensino
São Paulo
São Paulo
Recruiting
Americas Medical City
Rio de Janeiro
Brazil
Recruiting
Beneficencia Portuguesa de Sao Paulo
São Paulo
Brazil
Recruiting
Victoria Hospital - London Health Sciences Centre
London
Ontario
Recruiting
The Ottawa Hospital - General Campus
Ottawa
Ontario
Recruiting
Princess Margaret Cancer Center
Toronto
Ontario
Recruiting
Beijing Tong Ren Hospital, Capital Medical University
Beijing
China
Recruiting
+ 42 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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