A Study to Evaluate Glofitamab as a Single Agent vs. Investigator's Choice in Participants With Relapsed/Refractory Mantle Cell Lymphoma
- Conditions
- Lymphoma
- Interventions
- Registration Number
- NCT06084936
- Lead Sponsor
- Hoffmann-La Roche
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 182
- 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
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description BR or R-Len Rituximab Participants will receive bendamustine + rituximab for up to 6 cycles (cycle length = 28 days), or rituximab + lenalidomide (cycle length = 28 days) until disease progression. Glofitamab monotherapy Tocilizumab Participants will receive two intravenous (IV) obinutuzumab pretreatments prior to receiving IV glofitamab for 12 cycles (cycle length = 21 days). Glofitamab monotherapy Glofitamab Participants will receive two intravenous (IV) obinutuzumab pretreatments prior to receiving IV glofitamab for 12 cycles (cycle length = 21 days). Glofitamab monotherapy Obinutuzumab Participants will receive two intravenous (IV) obinutuzumab pretreatments prior to receiving IV glofitamab for 12 cycles (cycle length = 21 days). BR or R-Len Bendamustine Participants will receive bendamustine + rituximab for up to 6 cycles (cycle length = 28 days), or rituximab + lenalidomide (cycle length = 28 days) until disease progression. BR or R-Len Tocilizumab Participants will receive bendamustine + rituximab for up to 6 cycles (cycle length = 28 days), or rituximab + lenalidomide (cycle length = 28 days) until disease progression. BR or R-Len Lenalidomide Participants will receive bendamustine + rituximab for up to 6 cycles (cycle length = 28 days), or rituximab + lenalidomide (cycle length = 28 days) until disease progression.
- Primary Outcome Measures
Name Time Method Progression-free survival (PFS) From randomization to the first occurrence of disease progression or death from any cause (up to approximately 24 months)
- Secondary Outcome Measures
Name Time Method Objective response rate (ORR) Up to approximately 24 months 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) Up to approximately 24 months 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."
Complete response (CR) rate Up to approximately 24 months Overall survival (OS) From randomization to death from any cause (up to approximately 24 months) Time to deterioration in lymphoma symptoms 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) Incidence of anti-drug antibodies (ADAs) Up to approximately 24 months Investigator-assessed CR rate Up to approximately 24 months Duration of Complete Response (DOCR) 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) Proportion of participants reporting each response option for item GP5 from the Functional Assessment of Cancer Therapy - General (FACT-G) subscale Up to approximately 24 months Change from baseline in lymphoma symptoms at each cycle as assessed by the FACT-Lym LymS Up to approximately 24 months Time to deterioration in physical functioning/fatigue From randomization to a 10-point decrease in physical functioning/10-point increase in fatigue compared to baseline (up to approximately 24 months) Investigator-assessed PFS From randomization to disease progression or death from any cause (up to approximately 24 months) Investigator-assessed ORR Up to approximately 24 months Duration of Response (DOR) 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) 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 Up to approximately 24 months Serum concentration of glofitamab Up to approximately 24 months
Trial Locations
- Locations (74)
CHU NANTES - Hôtel Dieu
🇫🇷Nantes, France
ICTR Curitiba
🇧🇷Curitiba, Paraná, Brazil
Chongqing Cancer Hospital
🇨🇳Chongqing, China
Fujian Provincial Cancer Hospital
🇨🇳Fuzhou City, China
Auxilio Mutuo Cancer Center
🇵🇷San Juan, Puerto Rico
Alta Bates Summit Medical Center
🇺🇸Berkeley, California, United States
City of Hope Cancer Center
🇺🇸Duarte, California, United States
University of California Los Angeles (UCLA) - Cancer Care - Santa Monica
🇺🇸Santa Monica, California, United States
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
University of Miami
🇺🇸Coral Gables, Florida, United States
Indiana University
🇺🇸Indianapolis, Indiana, United States
University of Michigan Health System
🇺🇸Ann Arbor, Michigan, United States
St. Luke's Hospital
🇺🇸Chesterfield, Missouri, United States
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
University of Rochester
🇺🇸Rochester, New York, United States
Medical University of S. Carolina
🇺🇸Charleston, South Carolina, United States
Avera Cancer Institute
🇺🇸Sioux Falls, South Dakota, United States
Renovatio Clinical - El Paso
🇺🇸El Paso, Texas, United States
Renovatio Clinical
🇺🇸The Woodlands, Texas, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
West Virginia University
🇺🇸Morgantown, West Virginia, United States
Calvary Mater Newcastle
🇦🇺Waratah, New South Wales, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Epworth Hospital
🇦🇺Richmond, Victoria, Australia
Hospital Sao Rafael - HSR
🇧🇷Salvador, Bahia, Brazil
Hospital Mae de Deus
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Hospital Paulistano
🇧🇷Sao Paulo, São Paulo, Brazil
Hospital Alemao Oswaldo Cruz
🇧🇷Sao Paulo, São Paulo, Brazil
Hospital A. C. Camargo
🇧🇷Sao Paulo, São Paulo, Brazil
Instituto D'Or Pesquisa e Ensino
🇧🇷Sao Paulo, São Paulo, Brazil
Americas Medical City
🇧🇷Rio de Janeiro, Brazil
Beneficencia Portuguesa de Sao Paulo
🇧🇷São Paulo, Brazil
Victoria Hospital - London Health Sciences Centre
🇨🇦London, Ontario, Canada
The Ottawa Hospital - General Campus
🇨🇦Ottawa, Ontario, Canada
Princess Margaret Cancer Center
🇨🇦Toronto, Ontario, Canada
Beijing Tong Ren Hospital, Capital Medical University
🇨🇳Beijing, China
The First Hospital of Jilin University
🇨🇳Changchun City, China
West China Hospital of Sichuan University
🇨🇳Chengdu City, China
Sun yat-sen University Cancer Center
🇨🇳Guangzhou, China
Guangxi Cancer Hospital of Guangxi Medical University
🇨🇳Nanning City, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, China
The First Affiliated Hospital of China Medical University
🇨🇳Shenyang City, China
The First Affiliated Hospital of Wenzhou Medical University
🇨🇳Wenzhou City, China
Henan Cancer Hospital
🇨🇳Zhengzhou City, China
The First Affiliated Hospital of Zhengzhou University
🇨🇳Zhengzhou, China
Hopital Claude Huriez
🇫🇷Lille, France
Hopital Saint Eloi
🇫🇷Montpellier, France
INSTITUT CURIE_SITE PARIS - Service d'Oncologie Médicale.
🇫🇷Paris, France
Hopital Necker
🇫🇷Paris, France
Policlinico S.Orsola-Malpighi
🇮🇹Bologna, Emilia-Romagna, Italy
Humanitas Gavazzeni
🇮🇹Bergamo, Lombardia, Italy
Irccs Istituto Europeo Di Oncologia (IEO)
🇮🇹Milano, Lombardia, Italy
SC Ematologia, AO SS. Antonio e Biagio e C. Arrigo
🇮🇹Alessandria, Piemonte, Italy
A.O. Città della Salute e della Scienza D - Osp. S. Giov. Battista Molinette
🇮🇹Torino, Piemonte, Italy
Chungnam National University Hospital
🇰🇷Daejeon, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Hospital Universitario Puerta del Mar
🇪🇸Cádiz, Cadiz, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Complejo Hospitalario Universitario A Coruña (CHUAC)
🇪🇸La Coruna, Spain
Hospital General Universitario J.M Morales Meseguer
🇪🇸Murcia, Spain
Skånes University Hospital, Skånes Department of Onclology
🇸🇪Lund, Sweden
Akademiska sjukhuset, Onkologkliniken
🇸🇪Uppsala, Sweden
National Taiwan Universtiy Hospital
🇨🇳Taipei, Taiwan
Chang Gung Medical Foundation - Linkou
🇨🇳Taoyuan, Taiwan
NHS Greater Glasgow and Clyde
🇬🇧Glasgow, United Kingdom
Lincolnshire County Hospital
🇬🇧Lincoln, United Kingdom
University College London Hospital
🇬🇧London, United Kingdom
Christie Hospital Nhs Trust
🇬🇧Manchester, United Kingdom
Oxford Churchill Hospital
🇬🇧Oxford, United Kingdom
Derriford Hospital
🇬🇧Plymouth, United Kingdom