A Study Evaluating the Efficacy and Safety of Mosunetuzumab in Combination With Lenalidomide in Comparison to Rituximab in Combination With Lenalidomide With a US Extension of Mosunetuzumab in Combination With Lenalidomide in Participants With Follicular Lymphoma

NCT ID: NCT04712097

Last Updated: 2026-01-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

478 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-10-27

Study Completion Date

2029-12-31

Brief Summary

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This study will evaluate the efficacy and safety of mosunetuzumab in combination with lenalidomide (M + Len) compared to rituximab in combination with lenalidomide (R + Len) in participants with relapsed or refractory (R/R) follicular lymphoma (FL) who have received at least one line of prior systemic therapy.

Detailed Description

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Conditions

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Relapsed or Refractory Follicular Lymphoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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M + Len (Arm A)

Participants will receive mosunetuzumab for 12 cycles, plus lenalidomide from cycles 2-12 (Cycle length = 21 days for Cycle 1; cycle length = 28 days for Cycles 2-12)

Group Type EXPERIMENTAL

Mosunetuzumab

Intervention Type DRUG

Participants will receive intravenous (IV) mosunetuzumab in a step-up dosing schedule on Days 1, 8, and 15 of Cycle 1, and on Day 1 of Cycles 2-12

Lenalidomide

Intervention Type DRUG

Participants will receive oral lenalidomide once daily on Days 1-21 of Cycles 2-12 (M + Len) or Cycles 1-12 (R + Len)

Tociluzumab

Intervention Type DRUG

Tocilizumab will be administered as needed to manage cytokine release syndrome (CRS) events

R + Len (Arm B)

Participants will receive weekly rituximab in Cycle 1, then on Day 1 of Cycles 3, 5, 7, 9, and 11. Participants will also receive lenalidomide in Cycles 1-12. (Cycle length = 28 days for Cycles 1-12)

Group Type EXPERIMENTAL

Lenalidomide

Intervention Type DRUG

Participants will receive oral lenalidomide once daily on Days 1-21 of Cycles 2-12 (M + Len) or Cycles 1-12 (R + Len)

Rituximab

Intervention Type DRUG

Participants will receive IV rituximab on Days 1, 8, 15, and 22 of Cycle 1, then on Day 1 of Cycles 3, 5, 7, 9, and 11

Tociluzumab

Intervention Type DRUG

Tocilizumab will be administered as needed to manage cytokine release syndrome (CRS) events

M + Len (US Extension Arm C)

Participants will receive mosunetuzumab for 12 cycles, plus lenalidomide from cycles 2-12 (Cycle length = 21 days for Cycle 1; cycle length = 28 days for Cycles 2-12)

Group Type EXPERIMENTAL

Mosunetuzumab

Intervention Type DRUG

Participants will receive intravenous (IV) mosunetuzumab in a step-up dosing schedule on Days 1, 8, and 15 of Cycle 1, and on Day 1 of Cycles 2-12

Lenalidomide

Intervention Type DRUG

Participants will receive oral lenalidomide once daily on Days 1-21 of Cycles 2-12 (M + Len) or Cycles 1-12 (R + Len)

Tociluzumab

Intervention Type DRUG

Tocilizumab will be administered as needed to manage cytokine release syndrome (CRS) events

Interventions

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Mosunetuzumab

Participants will receive intravenous (IV) mosunetuzumab in a step-up dosing schedule on Days 1, 8, and 15 of Cycle 1, and on Day 1 of Cycles 2-12

Intervention Type DRUG

Lenalidomide

Participants will receive oral lenalidomide once daily on Days 1-21 of Cycles 2-12 (M + Len) or Cycles 1-12 (R + Len)

Intervention Type DRUG

Rituximab

Participants will receive IV rituximab on Days 1, 8, 15, and 22 of Cycle 1, then on Day 1 of Cycles 3, 5, 7, 9, and 11

Intervention Type DRUG

Tociluzumab

Tocilizumab will be administered as needed to manage cytokine release syndrome (CRS) events

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
* Histologically documented CD20+ FL (Grades 1-3a)
* Requiring systemic therapy assessed by investigator based on tumor size and/or Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria
* Received at least one prior systemic lymphoma therapy, which included prior immunotherapy or chemoimmunotherapy
* Availability of a representative tumor specimen and the corresponding pathology report at the time of relapse/persistence for confirmation of the diagnosis of FL. Pretreatment sample of at least 1 core-needle, excisional or incisional tumor biopsy is required. Cytological or fine-needle aspiration samples are not acceptable. Fresh pretreatment biopsy is preferred. Patients who are unable to undergo biopsy procedures may be eligible for study enrollment if an archival tumor tissue sample (preferably from the most recent relapse/persistence) as paraffin blocks or at least 15 unstained slides, or in accordance with local regulatory requirements, can be sent to the Sponsor.
* Adequate hematologic function (unless due to underlying lymphoma, per the investigator)
* Agreement to comply with all local requirements of the lenalidomide risk minimization plan, which includes the global pregnancy prevention program.
* For women of childbearing potential: Agreement to remain abstinent (refrain from heterosexual intercourse) or use 2 adequate methods of contraception, including at least 1 method with a failure rate of \< 1% per year, for at least 28 days prior to Day 1 of Cycle 1, during the treatment period (including periods of treatment interruption), and for at least 28 days after the last dose of lenalidomide, 3 months after the final dose of tocilizumab (if applicable), mosunetuzumab, and 12 months after final dose of rituximab. Women must refrain from donating eggs during this same period.
* For men: Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm, as defined: With female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 28 days after last dose of lenalidomide, 3 months after the final dose of tocilizumab (if applicable), mosunetuzumab and 12 months after the final dose of rituximab. Men must refrain from donating sperm during this same period.

Exclusion Criteria

* Grade 3b FL
* Any history of disease transformation and/or diffuse-large B cell lymphoma (DLBCL)
* Documented refractoriness to lenalidomide, defined as no response (partial response or complete response) or relapse within 6 months of therapy
* Active or history of CNS lymphoma or leptomeningeal infiltration
* Prior standard or investigational anti-cancer therapy as specified: Lenalidomide exposure within 12 months prior to Day 1 of Cycle 1; Chimeric antigen receptor T cell therapy within 30 days prior to Day 1 of Cycle 1; Radioimmunoconjugate within 12 weeks prior to Day 1 of Cycle 1; Monoclonal antibody or antibody-drug conjugate within 4 weeks prior to Cycle 1 Day 1; Treatment with any anti-cancer agent (investigational or otherwise) within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to first dose of study treatment
* Clinically significant toxicity (other than alopecia) from prior treatment that has not resolved to Grade \</= 1 (per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0) prior to Day 1 of Cycle 1
* Treatment with systemic immunosuppressive medications, including, but not limited to prednisone (\> 20 mg), azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents within 2 weeks prior to Day 1 of Cycle 1
* History of solid organ transplantation
* History of severe allergic or anaphylactic reaction to humanized, chimeric or murine monoclonal antibodies
* Known sensitivity or allergy to murine products
* Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary (CHO) cells or any component of the mosunetuzumab, rituximab, tocilizumab, lenalidomide, or thalidomide formulation, including mannitol
* History of erythema multiforme, Grade \>/= 3 rash, or blistering following prior treatment with immunomodulatory derivatives
* History of interstitial lung disease, drug-induced pneumonitis, and autoimmune pneumonitis
* Known active bacterial, viral, fungal, or other infection, or any major episode of infection requiring treatment with IV antibiotics within 4 weeks of Day 1 of Cycle 1
* Known or suspected chronic active Epstein-Barr virus (EBV) infection
* Known or suspected history of hemophagocytic lymphohistiocytosis
* Clinically significant history of liver disease, including viral or other hepatitis, or cirrhosis
* Active Hepatitis B infection
* Active Hepatitis C infection
* Known history of HIV positive status
* History of progressive multifocal leukoencephalopathy (PML)
* Administration of a live, attenuated vaccine within 4 weeks before first dose of study treatment or anticipation that such a live attenuated vaccine will be required during the study
* Other malignancy that could affect compliance with the protocol or interpretation of results
* Active autoimmune disease requiring treatment
* History of autoimmune disease, including, but not limited to: myocarditis, pneumonitis, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
* Prior allogeneic stem cell transplantation
* Contraindication to treatment for thromboembolism prophylaxis
* Evidence of any significant, uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including, but not limited to, significant cardiovascular disease (e.g., New York Heart Association Class III or IV cardiac disease, myocardial infarction within the previous 6 months, unstable arrhythmia, or unstable angina) or significant pulmonary disease (such as obstructive pulmonary disease or history of bronchospasm)
* Major surgical procedure other than for diagnosis within 28 days prior to Day 1 of Cycle 1 Day 1 or anticipation of a major surgical procedure during the course of the study
* Pregnant or lactating or intending to become pregnant during the study
* Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study, or which could affect compliance with the protocol or interpretation of results
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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City of Hope Comprehensive Cancer Center

Duarte, California, United States

Site Status

Winship Cancer Institute

Atlanta, Georgia, United States

Site Status

Fort Wayne Medical Oncology and Hematology, Inc

Fort Wayne, Indiana, United States

Site Status

Investigative Clinical Research of Indiana, LLC

Noblesville, Indiana, United States

Site Status

Johns Hopkins Uni

Baltimore, Maryland, United States

Site Status

University of Michigan Health System

Ann Arbor, Michigan, United States

Site Status

Cancer & Hematology Center of West Michigan

Grand Rapids, Michigan, United States

Site Status

Washington University

St Louis, Missouri, United States

Site Status

NYU Long Island Hospital

Mineola, New York, United States

Site Status

NYU Langone Ambulatory Care Center

New York, New York, United States

Site Status

Montefiore Medical Center - Montefiore Medical Park

The Bronx, New York, United States

Site Status

Montefiore Medical Center

The Bronx, New York, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Wake Forest Univ Health Svcs

Winston-Salem, North Carolina, United States

Site Status

Baylor University Medical Center

Dallas, Texas, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Kadlec Clinic Hematology and Oncology

Kennewick, Washington, United States

Site Status

Calvary Mater Newcastle

Waratah, New South Wales, Australia

Site Status

Princess Alexandra Hospital Woolloongabba

Woolloongabba, Queensland, Australia

Site Status

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Site Status

Geelong Hospital

Geelong, Victoria, Australia

Site Status

ICTR Curitiba

Curitiba, Paraná, Brazil

Site Status

Hospital das Clinicas - UFRGS

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

Hospital Mae de Deus

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

Hospital Alemao Oswaldo Cruz

São Paulo, São Paulo, Brazil

Site Status

Peking University First Hospital

Beijing, , China

Site Status

Beijing Cancer Hospital

Beijing, , China

Site Status

Peking University Third Hospital

Beijing, , China

Site Status

The First Hospital of Jilin University

Changchun, , China

Site Status

Cancer Center, Sun Yat-sen University of Medical Sciences

Guangzhou, , China

Site Status

Harbin Medical University Cancer Hospital

Harbin, , China

Site Status

The 1st Affiliated Hospital of Nanchang Unversity

Nanchang, , China

Site Status

Jiangsu Province Hospital

Nanjing, , China

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Fudan University Shanghai Cancer Center

Shanghai, , China

Site Status

Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences

Tianjin, , China

Site Status

Union Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, , China

Site Status

Tongji Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, , China

Site Status

The First Affiliated Hospital of Xiamen University

Xiamen, , China

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Zhejiang Cancer Hospital

Zhejiang, , China

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The First Affiliated Hospital of Zhengzhou University

Zhengzhou, , China

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Centre Hospitalier de La Cote Basque

Bayonne, , France

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Ch De Chambery

Chambéry, , France

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Hopital Henri Mondor

Créteil, , France

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Hopital Claude Huriez

Lille, , France

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Institut Paoli Calmettes

Marseille, , France

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CHU Saint Eloi

Montpellier, , France

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CHU NANTES - Hôtel Dieu

Nantes, , France

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Centre Antoine Lacassagne

Nice, , France

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CHU de Nîmes - Hôpital Carémeau

Nîmes, , France

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Hôpital Saint-Louis

Paris, , France

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Hopital Saint Antoine

Paris, , France

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Hopital De Haut Leveque

Pessac, , France

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Ch Lyon Sud

Pierre-Bénite, , France

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Hopital De La Miletrie

Poitiers, , France

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CHU de Reims

Reims, , France

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CHU Pontchaillou

Rennes, , France

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Centre Henri Becquerel

Rouen, , France

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ICANS

Strasbourg, , France

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Vivantes Klinikum Am Urban Klinik für Innere Medizin Hämatologie und Onkologie

Berlin, , Germany

Site Status

BAG Freiberg-Richter, Jacobasch, Illmer, Wolf

Dresden, , Germany

Site Status

Universitätsklinikum Halle

Halle, , Germany

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Uniklinik Heidelberg, Medizinische Klinik & Poliklinik V

Heidelberg, , Germany

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Klinik und Poliklinik f. Innere Medizin III des Universitätsklinikums Regensburg

Regensburg, , Germany

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Universitätsklinik Rostock

Rostock, , Germany

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Universtitätsklinikum Ulm

Ulm, , Germany

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A.O. Universitaria Policlinico S.Orsola-Malpighi Di Bologna

Bologna, Emilia-Romagna, Italy

Site Status

U.O. Ematologia AUSL Ravenna

Ravenna, Emilia-Romagna, Italy

Site Status

Ospedale V. Cervello

Palermo, Sicily, Italy

Site Status

Ospedali Riuniti Umberto I

Ancona, The Marches, Italy

Site Status

Azienda Ospedaliera Universitaria Careggi

Florence, Tuscany, Italy

Site Status

Ematologia/immunologia Clinica Azienda Ospedaliera Policlinico di Padova

Padua, Veneto, Italy

Site Status

Aichi Cancer Center

Aichi, , Japan

Site Status

National Cancer Center Hospital East

Chiba, , Japan

Site Status

University Hospital Kyoto Prefectural University of Medicine

Kyoto, , Japan

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Mie University Hospital

Mie, , Japan

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Tohoku University Hospital

Miyagi, , Japan

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Okayama University Hospital

Okayama, , Japan

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National Cancer Center Hospital

Tokyo, , Japan

Site Status

The Cancer Institute Hospital of JFCR

Tokyo, , Japan

Site Status

Uniwersyteckie Centrum Kliniczne

Gdansk, , Poland

Site Status

Szpitale Pomorskie Sp. z o. o.

Gdynia, , Poland

Site Status

Pratia Onkologia Katowice

Katowice, , Poland

Site Status

Uniwersytecki Szpital Kliniczny w Poznaniu

Późna, , Poland

Site Status

Instytut Hematologii i Transfuzjologii

Warsaw, , Poland

Site Status

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu

Wroc?aw, , Poland

Site Status

City Clinical Botkin's Hospital

Moscow, , Russia

Site Status

Penza Regional Oncology Dispensary

Penza, , Russia

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Pusan National University Hospital

Busan, , South Korea

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Seoul National University Bundang Hospital

Seongnam-si, , South Korea

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Samsung Medical Center

Seoul, , South Korea

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Seoul National University Hospital

Seoul, , South Korea

Site Status

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Site Status

Asan Medical Center

Seoul, , South Korea

Site Status

Seoul St Mary's Hospital

Seoul, , South Korea

Site Status

Hospital de Donostia

Guipuzcoa, Guipuzcoa, Spain

Site Status

Hospital Universitario la Paz

Madrid, , Spain

Site Status

Hospital General Universitario J.M Morales Meseguer

Murcia, , Spain

Site Status

Hospital Universitario Virgen del Rocio

Seville, , Spain

Site Status

Hospital Clinico Universitario de Valencia

Valencia, , Spain

Site Status

Chang Gung Medical Foundation - Kaohsiung;Oncology

Kaoisung, , Taiwan

Site Status

National Taiwan Universtiy Hospital

Taipei, , Taiwan

Site Status

Taipei Veterans General Hospital

Taipei, , Taiwan

Site Status

Chang Gung Medical Foundation - Linkou

Taoyuan District, , Taiwan

Site Status

Hacettepe Uni Medical Faculty

Ankara, , Turkey (Türkiye)

Site Status

Atakent Acibadem Private Hosptial Halkali Merkez Mh.,

Istanbul, , Turkey (Türkiye)

Site Status

Marmara Ün?Vers?Tes? ?Stanbul Pend?K E??T?M Ve Ara?Tirma Hastanes?

Istanbul, , Turkey (Türkiye)

Site Status

Koc Universitesi (KU) Tip Fakultesi (Koc University School of Medicine)

Sarıyer, , Turkey (Türkiye)

Site Status

Royal Cornwall Hospitals NHS Trust

Cornwall, , United Kingdom

Site Status

Gloucestershire Royal Hospital

Gloucester, , United Kingdom

Site Status

Hammersmith Hospital

London, , United Kingdom

Site Status

Nottingham City Hospital

Nottingham, , United Kingdom

Site Status

Torbay Hospital

Torquay, , United Kingdom

Site Status

Countries

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United States Australia Brazil China France Germany Italy Japan Poland Russia South Korea Spain Taiwan Turkey (Türkiye) United Kingdom

Other Identifiers

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2020-005239-53

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GO42909

Identifier Type: -

Identifier Source: org_study_id

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