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

Официальное название

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

Обзор

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).

Вмешательства

• Препарат Obinutuzumab
  Participants will receive two 1000 mg pretreatments of intravenous (IV) obinutuzumab from Cycle 1 Day 1
• Препарат Glofitamab
  Participants will receive IV glofitamab beginning Cycle 1 Day 8 for 12 cycles (cycle length = 21 days).
• Препарат 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).
• Препарат Bendamustine
  Participants will receive IV bendamustine on Days 1 and 2 Q4W for 6 cycles (cycle length = 28 days).
• Препарат Lenalidomide
  Participants will receive oral lenalidomide once daily on Days 1-21 Q4W until disease progression.
• Препарат Tocilizumab
  Participants will receive IV tocilizumab as required to manage cytokine release syndrome (CRS) events.

Первичные конечные точки

• Progression-free survival (PFS) [Срок оценки: From randomization to the first occurrence of disease progression or death from any cause (up to approximately 24 months)]

Вторичные конечные точки (12)

• Complete response (CR) rate [Срок оценки: Up to approximately 24 months]
• Objective response rate (ORR) [Срок оценки: Up to approximately 24 months]
• Overall survival (OS) [Срок оценки: From randomization to death from any cause (up to approximately 24 months)]
• Time to deterioration in physical functioning/fatigue [Срок оценки: 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 [Срок оценки: From randomization to disease progression or death from any cause (up to approximately 24 months)]
• Investigator-assessed CR rate [Срок оценки: Up to approximately 24 months]
• Investigator-assessed ORR [Срок оценки: Up to approximately 24 months]
• Duration of Complete Response (DOCR) [Срок оценки: 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)]
• Duration of Response (DOR) [Срок оценки: 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 [Срок оценки: Up to approximately 24 months]
• Time to deterioration in lymphoma symptoms [Срок оценки: 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)]
• 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 [Срок оценки: Up to approximately 24 months]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 24 центра

• Alta Bates Summit Medical Center — Berkeley
• City of Hope Cancer Center — Duarte
• Valkyrie Clinical Trials — Los Angeles
• University of California Los Angeles (UCLA) - Cancer Care - Santa Monica — Santa Monica
• Yale Cancer Center — New Haven
• Georgetown University — Washington D.C.
• University of Miami — Coral Gables
• Moffitt Cancer Center — Tampa
• … и ещё 16 центров

Китай · 12 центров

• Beijing Tong Ren Hospital, Capital Medical University — Пекин
• The First Hospital of Jilin University — Changchun
• West China Hospital of Sichuan University — Чэнду
• Chongqing Cancer Hospital — Чунцин
• Fujian Provincial Cancer Hospital — Фучжоу
• Sun yat-sen University Cancer Center — Гуанчжоу
• Guangxi Cancer Hospital of Guangxi Medical University — Nanning
• Fudan University Shanghai Cancer Center — Шанхай
• … и ещё 4 центра

Бразилия · 9 центров

• Hospital Sao Rafael - HSR — Salvador
• Ictrials Pesquisa e Desenvolvimento — Curitiba
• Hospital Mae de Deus — Porto Alegre
• Hospital Paulistano — São Paulo
• Hospital Alemao Oswaldo Cruz — São Paulo
• Hospital A. C. Camargo — São Paulo
• Instituto D'Or Pesquisa e Ensino — São Paulo
• Americas Medical City — Rio de Janeiro
• … и ещё 1 центр

Великобритания · 6 центров

• NHS Greater Glasgow and Clyde — Glasgow
• Lincolnshire County Hospital — Lincoln
• University College London Hospital — London
• Christie Hospital Nhs Trust — Manchester
• … и ещё 2 центра

Франция · 5 центров

• Hopital Claude Huriez — Lille
• Hopital Saint Eloi — Montpellier
• CHU NANTES - Hôtel Dieu — Nantes
• INSTITUT CURIE_SITE PARIS - Service d'Oncologie Médicale. — Paris
• Hopital Necker — Paris

Италия · 5 центров

• Policlinico S.Orsola-Malpighi — Bologna
• Humanitas Gavazzeni — Bergamo
• Irccs Istituto Europeo Di Oncologia (IEO) — Milan
• SC Ematologia, AO SS. Antonio e Biagio e C. Arrigo — Alessandria
• A.O. Città della Salute e della Scienza D - Osp. S. Giov. Battista Molinette — Turin

South Korea · 5 центров

• Chungnam National University Hospital — Daejeon
• Severance Hospital, Yonsei University Health System — Seoul
• Seoul National University Hospital — Seoul
• Asan Medical Center — Seoul
• Samsung Medical Center — Seoul

Испания · 5 центров

• Hospital Universitario Puerta del Mar — Cadiz
• Complejo Hospitalario Universitario A Coruña (CHUAC) — A Coruña
• Hospital Universitari Vall d'Hebron — Barcelona
• Hospital Clinic de Barcelona — Barcelona
• Hospital General Universitario J.M Morales Meseguer — Murcia

Австралия · 3 центра

• Calvary Mater Newcastle — Waratah
• Royal Adelaide Hospital — Adelaide
• Epworth Hospital — Richmond

Канада · 3 центра

• Victoria Hospital - London Health Sciences Centre — London
• The Ottawa Hospital - General Campus — Ottawa
• Princess Margaret Cancer Center — Toronto

Швеция · 2 центра

• Skånes University Hospital, Skånes Department of Onclology — Lund
• Akademiska sjukhuset, Onkologkliniken — Uppsala

Тайвань · 2 центра

• National Taiwan Universtiy Hospital — Taipei
• Chang Gung Medical Foundation - Linkou — Taoyuan

Пуэрто-Рико · 1 центр

• Auxilio Mutuo Cancer Center — San Juan

Идентификаторы

NCT: NCT06084936 · GO43878

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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