Clinical trial NCT06084936: A Study to Evaluate Glofitamab as a Single Agent vs. Investigator's Choice in Participants With Relapsed/Refractory Mantle Cell Lymphoma
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
Overall status: RECRUITING
Phase: PHASE3
Conditions: Lymphoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2023-10-16
Enrollment: 182
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: From randomization to the first occurrence of disease progression or death from any cause (up to approximately 24 months)
Secondary outcomes:
measure: Complete response (CR) rate
timeFrame: Up to approximately 24 months
measure: Objective response rate (ORR)
timeFrame: Up to approximately 24 months
measure: Overall survival (OS)
timeFrame: From randomization to death from any cause (up to approximately 24 months)
measure: Time to deterioration in physical functioning/fatigue
timeFrame: From randomization to a 10-point decrease in physical functioning/10-point increase in fatigue compared to baseline (up to approximately 24 months)
measure: Investigator-assessed PFS
timeFrame: From randomization to disease progression or death from any cause (up to approximately 24 months)
measure: Investigator-assessed CR rate
timeFrame: Up to approximately 24 months
measure: Investigator-assessed ORR
timeFrame: Up to approximately 24 months
measure: Duration of Complete Response (DOCR)
timeFrame: 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)
measure: Duration of Response (DOR)
timeFrame: 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)
measure: Proportion of participants reporting each response option for item GP5 from the Functional Assessment of Cancer Therapy - General (FACT-G) subscale
timeFrame: Up to approximately 24 months
measure: Time to deterioration in lymphoma symptoms
timeFrame: 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)
measure: 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
timeFrame: Up to approximately 24 months
measure: 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)
timeFrame: Up to approximately 24 months
measure: Change from baseline in lymphoma symptoms at each cycle as assessed by the FACT-Lym LymS
timeFrame: Up to approximately 24 months
measure: Serum concentration of glofitamab
timeFrame: Up to approximately 24 months
measure: Incidence of anti-drug antibodies (ADAs)
timeFrame: Up to approximately 24 months
Other outcomes:
Locations:
city: Berkeley
country: United States
facility: Alta Bates Summit Medical Center
state: California
city: Duarte
country: United States
facility: City of Hope Cancer Center
state: California
city: Santa Monica
country: United States
facility: University of California Los Angeles (UCLA) - Cancer Care - Santa Monica
state: California
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Coral Gables
country: United States
facility: University of Miami
state: Florida
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Chesterfield
country: United States
facility: St. Luke's Hospital
state: Missouri
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Charleston
country: United States
facility: Medical University of S. Carolina
state: South Carolina
city: Sioux Falls
country: United States
facility: Avera Cancer Institute
state: South Dakota
city: El Paso
country: United States
facility: Renovatio Clinical - El Paso
state: Texas
city: The Woodlands
country: United States
facility: Renovatio Clinical
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
city: Waratah
country: Australia
facility: Calvary Mater Newcastle
state: New South Wales
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Richmond
country: Australia
facility: Epworth Hospital
state: Victoria
city: Salvador
country: Brazil
facility: Hospital Sao Rafael - HSR
state: Bahia
city: Curitiba
country: Brazil
facility: ICTR Curitiba
state: Paraná
city: Porto Alegre
country: Brazil
facility: Hospital Mae de Deus
state: Rio Grande Do Sul
city: Sao Paulo
country: Brazil
facility: Hospital Paulistano
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Hospital Alemao Oswaldo Cruz
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Hospital A. C. Camargo
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Instituto D'Or Pesquisa e Ensino
state: São Paulo
city: Rio de Janeiro
country: Brazil
facility: Americas Medical City
city: São Paulo
country: Brazil
facility: Beneficencia Portuguesa de Sao Paulo
city: London
country: Canada
facility: Victoria Hospital - London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital - General Campus
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Center
state: Ontario
city: Beijing
country: China
facility: Beijing Tong Ren Hospital, Capital Medical University
city: Changchun City
country: China
facility: The First Hospital of Jilin University
city: Chengdu City
country: China
facility: West China Hospital of Sichuan University
city: Chongqing
country: China
facility: Chongqing Cancer Hospital
city: Fuzhou City
country: China
facility: Fujian Provincial Cancer Hospital
city: Guangzhou
country: China
facility: Sun yat-sen University Cancer Center
city: Nanning City
country: China
facility: Guangxi Cancer Hospital of Guangxi Medical University
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
city: Shenyang City
country: China
facility: The First Affiliated Hospital of China Medical University
city: Wenzhou City
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
city: Zhengzhou City
country: China
facility: Henan Cancer Hospital
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
city: Lille
country: France
facility: Hopital Claude Huriez
city: Montpellier
country: France
facility: Hopital Saint Eloi
city: Nantes
country: France
facility: CHU NANTES - Hôtel Dieu
city: Paris
country: France
facility: INSTITUT CURIE_SITE PARIS - Service d'Oncologie Médicale.
city: Paris
country: France
facility: Hopital Necker
city: Bologna
country: Italy
facility: Policlinico S.Orsola-Malpighi
state: Emilia-Romagna
city: Bergamo
country: Italy
facility: Humanitas Gavazzeni
state: Lombardia
city: Milano
country: Italy
facility: Irccs Istituto Europeo Di Oncologia (IEO)
state: Lombardia
city: Alessandria
country: Italy
facility: SC Ematologia, AO SS. Antonio e Biagio e C. Arrigo
state: Piemonte
city: Torino
country: Italy
facility: A.O. Città della Salute e della Scienza D - Osp. S. Giov. Battista Molinette
state: Piemonte
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: San Juan
country: Puerto Rico
facility: Auxilio Mutuo Cancer Center
city: Cádiz
country: Spain
facility: Hospital Universitario Puerta del Mar
state: Cadiz
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: La Coruna
country: Spain
facility: Complejo Hospitalario Universitario A Coruña (CHUAC)
city: Murcia
country: Spain
facility: Hospital General Universitario J.M Morales Meseguer
city: Lund
country: Sweden
facility: Skånes University Hospital, Skånes Department of Onclology
city: Uppsala
country: Sweden
facility: Akademiska sjukhuset, Onkologkliniken
city: Taipei
country: Taiwan
facility: National Taiwan Universtiy Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Medical Foundation - Linkou
city: Glasgow
country: United Kingdom
facility: NHS Greater Glasgow and Clyde
city: Lincoln
country: United Kingdom
facility: Lincolnshire County Hospital
city: London
country: United Kingdom
facility: University College London Hospital
city: Manchester
country: United Kingdom
facility: Christie Hospital Nhs Trust
city: Oxford
country: United Kingdom
facility: Oxford Churchill Hospital
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: