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
- Conditions
- Relapsed or Refractory Follicular Lymphoma
- Interventions
- Registration Number
- NCT04712097
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
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
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 478
- 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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description M + Len (Arm A) Mosunetuzumab 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) M + Len (Arm A) Lenalidomide 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) M + Len (Arm A) Tociluzumab 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) R + Len (Arm B) Lenalidomide 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) R + Len (Arm B) Rituximab 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) R + Len (Arm B) Tociluzumab 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) M + Len (US Extension Arm C) Mosunetuzumab 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) M + Len (US Extension Arm C) Lenalidomide 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) M + Len (US Extension Arm C) Tociluzumab 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)
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) according to 2014 Lugano Response Criteria From randomization to the first occurrence of disease progression as determined by an independent review committee (IRC) or death from any cause (up to approximately 8.5 years)
- Secondary Outcome Measures
Name Time Method Objective Response Rate (ORR) Up to approximately 8.5 years Overall Survival (OS) From randomization to death from any cause (up to approximately 8.5 years) Duration of Objective Response (DOR) From the first occurrence of a documented objective response (complete response or partial response) to disease progression or death from any cause, whichever occurs first (up to approximately 8.5 years) Duration of Complete Reponse (DOCR) From the first occurrence of a documented CR to disease progression or death from any cause, whichever occurs first (up to approximately 8.5 years) Time to Deterioration in Physical Functioning and Fatigue, as Measured by the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30) Up to approximately 8.5 years Time to Deterioration in Lymphoma Symptoms, as Measured by the Functional Assessment of Cancer Therapy-Lymphoma Subscale (FACT-LymS) Up to approximately 8.5 years PFS as Determined by the Investigator From randomization to the first occurrence of disease progression or death from any cause (up to approximately 8.5 years) Complete Response Rate Up to approximately 8.5 years Percentage of Participants with Adverse Events (AEs) Up to approximately 8.5 years Serum Concentration of M + Len Up to approximately 8.5 years Area Under the Curve (AUC) of M + Len Up to approximately 8.5 years Percentage of Participants with Anti-Drug Antibodies (ADAs) Up to approximately 8.5 years Time to New Anti-Lymphoma Treatment (TTNALT) From randomization to the first documented administration of a new anti-lymphoma treatment (up to approximately 8.5 years)
Trial Locations
- Locations (113)
ICTR Curitiba
🇧🇷Curitiba, Paraná, Brazil
The First Affiliated Hospital of Zhengzhou University
🇨🇳Zhengzhou, China
Centre Hospitalier de La Cote Basque
🇫🇷Bayonne, France
Ch De Chambery
🇫🇷Chambery, France
Hopital Henri Mondor
🇫🇷Creteil, France
Hopital Claude Huriez
🇫🇷Lille, France
Institut Paoli Calmettes
🇫🇷Marseille, France
CHU Saint Eloi
🇫🇷Montpellier, France
CHU NANTES - Hôtel Dieu
🇫🇷Nantes, France
Centre Antoine Lacassagne
🇫🇷Nice, France
CHU de Nîmes - Hôpital Carémeau
🇫🇷Nimes, France
Hôpital Saint-Louis
🇫🇷Paris, France
Hopital Saint Antoine
🇫🇷Paris, France
Hopital De Haut Leveque
🇫🇷Pessac, France
Ch Lyon Sud
🇫🇷Pierre Benite, France
Hopital De La Miletrie
🇫🇷Poitiers, France
CHU de Reims
🇫🇷Reims, France
CHU Pontchaillou
🇫🇷Rennes, France
Centre Henri Becquerel
🇫🇷Rouen, France
ICANS
🇫🇷Strasbourg, France
Vivantes Klinikum Am Urban Klinik für Innere Medizin Hämatologie und Onkologie
🇩🇪Berlin, Germany
BAG Freiberg-Richter, Jacobasch, Illmer, Wolf
🇩🇪Dresden, Germany
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Poland
Zhejiang Cancer Hospital
🇨🇳Zhejiang, China
Seoul St Mary's Hospital
🇰🇷Seoul, Korea, Republic of
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States
Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
Fort Wayne Medical Oncology and Hematology, Inc
🇺🇸Fort Wayne, Indiana, United States
Investigative Clinical Research of Indiana, LLC
🇺🇸Noblesville, Indiana, United States
Johns Hopkins Uni
🇺🇸Baltimore, Maryland, United States
University of Michigan Health System
🇺🇸Ann Arbor, Michigan, United States
Cancer & Hematology Center of West Michigan
🇺🇸Grand Rapids, Michigan, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
Montefiore Medical Center - Montefiore Medical Park
🇺🇸Bronx, New York, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States
NYU Long Island Hospital
🇺🇸Mineola, New York, United States
NYU Langone Ambulatory Care Center
🇺🇸New York, New York, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Wake Forest Univ Health Svcs
🇺🇸Winston-Salem, North Carolina, United States
Baylor University Medical Center
🇺🇸Dallas, Texas, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Kadlec Clinic Hematology and Oncology
🇺🇸Kennewick, Washington, United States
Calvary Mater Newcastle
🇦🇺Waratah, New South Wales, Australia
Princess Alexandra Hospital Woolloongabba
🇦🇺Woolloongabba, Queensland, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Geelong Hospital
🇦🇺Geelong, Victoria, Australia
Hospital das Clinicas - UFRGS
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Hospital Mae de Deus
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Hospital Alemao Oswaldo Cruz
🇧🇷Sao Paulo, São Paulo, Brazil
Peking University First Hospital
🇨🇳Beijing City, China
Beijing Cancer Hospital
🇨🇳Beijing, China
Peking University Third Hospital
🇨🇳Beijing, China
The First Hospital of Jilin University
🇨🇳Changchun City, China
Cancer Center, Sun Yat-sen University of Medical Sciences
🇨🇳Guangzhou, China
Harbin Medical University Cancer Hospital
🇨🇳Harbin, China
The 1st Affiliated Hospital of Nanchang Unversity
🇨🇳Nanchang City, China
Jiangsu Province Hospital
🇨🇳Nanjing, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, China
Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
🇨🇳Shanghai, China
Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences
🇨🇳Tianjin City, China
Union Hospital Tongji Medical College Huazhong University of Science and Technology
🇨🇳Wuhan City, China
Tongji Hospital Tongji Medical College Huazhong University of Science and Technology
🇨🇳Wuhan City, China
The First Affiliated Hospital of Xiamen University
🇨🇳Xiamen, China
Universitätsklinikum Halle
🇩🇪Halle (Saale), Germany
Uniklinik Heidelberg, Medizinische Klinik & Poliklinik V
🇩🇪Heidelberg, Germany
Klinik und Poliklinik f. Innere Medizin III des Universitätsklinikums Regensburg
🇩🇪Regensburg, Germany
Universitätsklinik Rostock
🇩🇪Rostock, Germany
Universtitätsklinikum Ulm
🇩🇪Ulm, Germany
A.O. Universitaria Policlinico S.Orsola-Malpighi Di Bologna
🇮🇹Bologna, Emilia-Romagna, Italy
U.O. Ematologia AUSL Ravenna
🇮🇹Ravenna, Emilia-Romagna, Italy
Ospedali Riuniti Umberto I
🇮🇹Ancona, Marche, Italy
Ospedale V. Cervello
🇮🇹Palermo, Sicilia, Italy
Azienda Ospedaliera Universitaria Careggi
🇮🇹Firenze, Toscana, Italy
Ematologia/immunologia Clinica Azienda Ospedaliera Policlinico di Padova
🇮🇹Padova, Veneto, Italy
Aichi Cancer Center
🇯🇵Aichi, Japan
National Cancer Center Hospital East
🇯🇵Chiba, Japan
University Hospital Kyoto Prefectural University of Medicine
🇯🇵Kyoto, Japan
Mie University Hospital
🇯🇵Mie, Japan
Tohoku University Hospital
🇯🇵Miyagi, Japan
Okayama University Hospital
🇯🇵Okayama, Japan
National Cancer Center Hospital
🇯🇵Tokyo, Japan
The Cancer Institute Hospital of JFCR
🇯🇵Tokyo, Japan
Pusan National University Hospital
🇰🇷Busan, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Szpitale Pomorskie Sp. z o. o.
🇵🇱Gdynia, Poland
Pratia Onkologia Katowice
🇵🇱Katowice, Poland
Uniwersytecki Szpital Kliniczny w Poznaniu
🇵🇱Pozna?, Poland
Instytut Hematologii i Transfuzjologii
🇵🇱Warszawa, Poland
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu
🇵🇱Wroc?aw, Poland
City Clinical Botkin's Hospital
🇷🇺Moscow, Russian Federation
Penza Regional Oncology Dispensary
🇷🇺Penza, Russian Federation
Hospital de Donostia
🇪🇸Guipuzcoa, Spain
Hospital Universitario la Paz
🇪🇸Madrid, Spain
Hospital General Universitario J.M Morales Meseguer
🇪🇸Murcia, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
Chang Gung Medical Foundation - Kaohsiung;Oncology
🇨🇳Kaoisung, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei City, Taiwan
National Taiwan Universtiy Hospital
🇨🇳Taipei, Taiwan
Chang Gung Medical Foundation - Linkou
🇨🇳Taoyuan, Taiwan
Hacettepe Uni Medical Faculty
🇹🇷Ankara, Turkey
Atakent Acibadem Private Hosptial Halkali Merkez Mh.,
🇹🇷Istanbul, Turkey
Marmara Ün?Vers?Tes? ?Stanbul Pend?K E??T?M Ve Ara?Tirma Hastanes?
🇹🇷Istanbul, Turkey
Koc Universitesi (KU) Tip Fakultesi (Koc University School of Medicine)
🇹🇷Sariyer, Turkey
Royal Cornwall Hospitals NHS Trust
🇬🇧Cornwall, United Kingdom
Gloucestershire Royal Hospital
🇬🇧Gloucester, United Kingdom
Hammersmith Hospital
🇬🇧London, United Kingdom
Nottingham City Hospital
🇬🇧Nottingham, United Kingdom
Torbay Hospital
🇬🇧Torquay, United Kingdom