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

Relapsed or Refractory Follicular Lymphoma Clinical Trial

— Celestimo  

Official title:

Phase III Randomized, Open-Label, Multicenter Study Evaluating Efficacy and Safety of Mosunetuzumab in Combination With Lenalidomide in Comparison to Rituximab in Combination With Lenalidomide With a Non-Randomized Single Arm US Extension of Mosunetuzumab in Combination With Lenalidomide in Patients With Follicular Lymphoma After at Least One Line of Systemic Therapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04712097
• Other study ID #: GO42909
• Secondary ID: 2020-005239-53
• Status: Recruiting
• Phase: Phase 3
• Start date: October 27, 2021
• Est. completion date: May 1, 2029

Study information

• Verified date: June 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID: GO42909 https://forpatients.roche.com/
• Phone: 888-662-6728
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 474
• Est. completion date: May 1, 2029
• Est. primary completion date: August 25, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 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

• History of transformation of indolent disease to diffuse-large B cell lymphoma

• 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, 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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Follicular
• Relapsed or Refractory Follicular Lymphoma

Intervention

Drug:
• 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
• Lenalidomide
Participants will receive oral lenalidomide once daily on Days 1-21 of Cycles 2-12 (M + Len) or Cycles 1-12 (R + Len)
• 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
• Tociluzumab
Tocilizumab will be administered as needed to manage cytokine release syndrome (CRS) events

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital; Haematology Clinical Trials	Adelaide	South Australia
Australia	Geelong Hospital; Andrew Love Cancer Centre	Geelong	Victoria
Australia	Calvary Mater Newcastle	Waratah	New South Wales
Australia	Princess Alexandra Hospital Woolloongabba; Clinical Hematology and Medical Oncology	Woolloongabba	Queensland
Brazil	ICTR Curitiba	Curitiba	PR
Brazil	Hospital das Clinicas - UFRGS	Porto Alegre	RS
Brazil	Hospital Mae de Deus	Porto Alegre	RS
Brazil	Hospital Alemao Oswaldo Cruz	Sao Paulo	SP
China	Beijing Cancer Hospital	Beijing
China	Peking University Third Hospital	Beijing
China	Peking University First Hospital	Beijing City
China	The First Hospital of Jilin University	Changchun City
China	Cancer Center, Sun Yat-sen University of Medical Sciences; Department of Medical Oncology	Guangzhou City
China	Harbin Medical University Cancer Hospital	Harbin
China	The 1st Affiliated Hospital of Nanchang Unversity	Nanchang
China	Jiangsu Province Hospital	Nanjing
China	Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine	Shanghai
China	Fudan University Shanghai Cancer Center; Medical Oncology	Shanghai City
China	Tianjin Cancer Hospital	Tianjin
China	Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences	Tianjin City
China	Tongji Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan City
China	Union Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan City
China	The First Affiliated Hospital of Xiamen University	Xiamen
China	Zhejiang Cancer Hospital	Zhejiang
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou
France	Centre Hospitalier de La Cote Basque; Hematologie	Bayonne
France	Ch De Chambery; Hematologie Oncologie	Chambery
France	Hopital Henri Mondor; Hematologie Clinique	Creteil
France	Hopital Claude Huriez; Hematologie	Lille
France	Institut Paoli Calmettes	Marseille
France	CHU Saint Eloi; Service d'Hématologie Clinique	Montpellier
France	CHU NANTES - Hôtel Dieu; Service d'Hematologie Clinique	Nantes
France	Centre Antoine Lacassagne;B4 Hematologie Cancerologie	Nice
France	CHU de Nîmes - Hôpital Carémeau	Nimes
France	Hopital Saint Antoine; Hematologie Clinique	Paris
France	Hôpital Saint-Louis; Service d'Hématologie	Paris
France	Hopital De Haut Leveque; Hematologie Clinique	Pessac
France	Ch Lyon Sud; Hemato Secteur Jules Courmont	Pierre Benite
France	Hopital De La Miletrie; Hematologie Et Oncologie Medicale	Poitiers
France	CHU de Reims	Reims
France	CHU Pontchaillou	Rennes
France	Centre Henri Becquerel; Service Hématologie	Rouen
France	ICLN;Hopital De Jour Rdc	St Priest En Jarez
France	ICANS	Strasbourg
Germany	Universitätsklinikum Augsburg; II. Med. Klinik	Augsburg
Germany	Sozialstiftung Bamberg - Klinikum am Bruderwald, Med. Klinik V; Hämatologie und intern. Onkologie	Bamberg
Germany	CAMPUS BENJAMIN FRANKLIN CharitéCentrum 14 Med.Klinik f.Hämatologie u.Onkologie	Berlin
Germany	Vivantes Klinikum Am Urban Klinik für Innere Medizin Hämatologie und Onkologie	Berlin
Germany	Klinikum Chemnitz gGmbH, Klinik für Innere Medizin III, Hämatologie und Onkologie	Chemnitz
Germany	BAG Freiberg-Richter, Jacobasch, Illmer, Wolf; Gemeinschaftspraxis Hämatologie-Onkologie	Dresden
Germany	Marien-Hospital Klinik f.Hämatologie Onkologie u.Palliativmedizin	Düsseldorf
Germany	Medizinische Klinik IV, Hämatologie Universitätsklinikum Gießen	Giessen
Germany	Universitätsklinikum Halle; Klinik für Innere Medizin IV; Hämatologie und Onkologie	Halle (Saale)
Germany	Uniklinik Heidelberg, Medizinische Klinik & Poliklinik V	Heidelberg
Germany	Universitaetsklinikum des Saarlandes; medizinische Klinik und Poliklinik; Innere Medizin I	Homburg/Saar
Germany	Westpfalz-Klinikum GmbH; Innere Medizin 1, Hämatologie und internistischen Onkologie	Kaiserslautern
Germany	Uni-Klinikum-Schleswig-Holstein; Klinik für Innere Medizin II; Hämatologie und Onkologie	Kiel
Germany	Universitaetsklinikum Schleswig Holstein - Campus Luebeck; Haematologie, Onkologie	Luebeck
Germany	Klinikum der Universität München, Campus Großhadern; Medizinische Klinik und Poliklinik III	München
Germany	Klinik und Poliklinik f. Innere Medizin III des Universitätsklinikums Regensburg	Regensburg
Germany	Universitätsklinik Rostock; Klinik für Innere Med. III, Abteilung Hämatologie/Onkologie	Rostock
Germany	Universtitätsklinikum Ulm; Klinik für Innere Medizin III	Ulm
Italy	Ospedali Riuniti Umberto I; Clinica di Ematologia	Ancona	Marche
Italy	Giovanni Paolo II/I.R.C.C.S. Istituto Tumori	Bari	Puglia
Italy	A.O. Universitaria Policlinico S.Orsola-Malpighi Di Bologna	Bologna	Emilia-Romagna
Italy	Azienda Ospedaliera Universitaria Careggi	Florence	Toscana
Italy	Ospedale Maggiore Di Milano; U.O. Ematologia I - Padiglione Marcora	Milano	Lombardia
Italy	Ematologia/immunologia Clinica Azienda Ospedaliera Policlinico di Padova	Padova	Veneto
Italy	Ospedale V. Cervello; U.O. Ematologia E Trapianti	Palermo	Sicilia
Italy	U.O. Ematologia AUSL Ravenna	Ravenna	Emilia-Romagna
Italy	Ospedale Di Circolo E Fondazione Macchi; Ematologia	Varese	Lombardia
Japan	Aichi Cancer Center	Aichi
Japan	National Cancer Center Hospital East	Chiba
Japan	Hokkaido University Hospital	Hokkaido
Japan	Kumamoto University Hospital	Kumamoto
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	Kindai University Hospital	Osaka
Japan	Osaka Metropolitan University Hospital	Osaka
Japan	National Cancer Center Hospital	Tokyo
Japan	The Cancer Institute Hospital of JFCR	Tokyo
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Seoul St Mary's Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Szpitale Pomorskie Sp. z o. o.; Oddzia? Hematologii i Transplantologii Szpiku	Gdynia
Poland	Pratia Onkologia Katowice	Katowice
Poland	Oddzial Kliniczny Hematologii SPZOZ MSWiA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie	Olsztyn
Poland	Uniwersytecki Szpital Kliniczny w Poznaniu; Oddzial Hematologii i Transplantacji Szpiku	Pozna?
Poland	Instytut Hematologii i Transfuzjologii; Klinika Hematologii	Warszawa
Poland	Uniwersytecki Szpital Kliniczny; Klinika Hematologii, Nowotworów Krwi i Transplantacji Szpiku	Wroc?aw
Russian Federation	City Clinical Botkin's Hospital; City Hematological Center	Moscow	Moskovskaja Oblast
Russian Federation	FSBI "National Medical Research Center of Oncology N.N. Blokhin?	Moscow	Moskovskaja Oblast
Russian Federation	Regional Clinical Hospital N.A. Semashko; Hematology	Nizhny Novgorod	Niznij Novgorod
Russian Federation	Penza Regional Oncology Dispensary	Penza
Spain	Hospital de Donostia; Servicio de Oncologia	Guipuzcoa
Spain	Hospital Universitario la Paz; Servicio de Hematologia	Madrid
Spain	Hospital General Universitario J.M Morales Meseguer; Servicio de Hematología	Murcia
Spain	Hospital Universitario Virgen del Rocio; Servicio de Hematologia	Sevilla
Spain	Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia	Valencia
Taiwan	Chang Gung Medical Foundation - Kaohsiung; Oncology; Division of Hematology-Oncology	Kaoisung
Taiwan	National Taiwan Universtiy Hospital; Division of Hematology	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei City
Taiwan	Chang Gung Medical Foundation - Linkou; Division of Hematology- Oncology	Taoyuan
Turkey	Sanko University Faculty of Medicine	?eh?tkam?l
Turkey	Gulhane Training and Research Hospital	Ankara
Turkey	Hacettepe Uni Medical Faculty; Hematology	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	Erciyes Uni ; Hematology	Kayseri
Turkey	Koc Universitesi (KU) Tip Fakultesi (Koc University School of Medicine)	Sariyer
Turkey	Karadeniz Technical Uni School of Medicine; Hematology	Trabzon
Ukraine	Medical Center named after academician Yuri Prokopovich Spizhenko; Oncochemotherpy Department	Kapitanivka	KIEV Governorate
Ukraine	Municipal Noncommercial Institution Regional Center of Oncology	Kharkiv	Kharkiv Governorate
Ukraine	SIResearch Centre for Radiation Medicine of AMS of Ukraine; Department of Radiation Oncohematology	Kiev
Ukraine	National Institute of Cancer	Kyiv
Ukraine	Mykolayiv Regional Hospital	Mykolaiv	KIEV Governorate
Ukraine	Municipal Institution Zaporizhzhia Regional Clinical Hospital of Zaporizhzhia Regional Council	Zaporizhzhia	Kharkiv Governorate
United Kingdom	Royal Cornwall Hospitals NHS Trust	Cornwall
United Kingdom	Gloucestershire Royal Hospital; Haematology Department	Gloucester
United Kingdom	Hammersmith Hospital; Dept of Oncology	London
United Kingdom	Royal Marsden Hospital - Fulham	London
United Kingdom	Nottingham City Hospital; Dept of Haematology	Nottingham
United Kingdom	Royal Marsden Hospital; Dept of Medical Oncology	Sutton
United Kingdom	Torbay Hospital; Oncology	Torquay
United States	University of Michigan Health System; UMH Internal Medicine/Hematology-Oncology	Ann Arbor	Michigan
United States	Winship Cancer Institute	Atlanta	Georgia
United States	Johns Hopkins Uni ; Sidney Kimmel Comprehensive Care Center	Baltimore	Maryland
United States	Lynn Cancer Institute/Boca Raton Regional Hospital	Boca Raton	Florida
United States	Montefiore Medical Center	Bronx	New York
United States	Montefiore Medical Center - Montefiore Medical Park	Bronx	New York
United States	MD Anderson Cancer Center at Cooper	Camden	New Jersey
United States	Baylor University Medical Center; Baylor Sammons Cancer Center	Dallas	Texas
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	cCare	Encinitas	California
United States	Fort Wayne Medical Oncology and Hematology, Inc	Fort Wayne	Indiana
United States	Cancer & Hematology Center of West Michigan	Grand Rapids	Michigan
United States	MD Anderson Cancer Center	Houston	Texas
United States	Kadlec Clinic Hematology and Oncology	Kennewick	Washington
United States	NYU Long Island Hospital	Mineola	New York
United States	NYU Langone Ambulatory Care Center	New York	New York
United States	Investigative Clinical Research of Indiana, LLC	Noblesville	Indiana
United States	Washington University; Wash Uni. Sch. Of Med	Saint Louis	Missouri
United States	Wake Forest Univ Health Svcs; Section on Hem and Onc	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  China,  France,  Germany,  Italy,  Japan,  Korea, Republic of,  Poland,  Russian Federation,  Spain,  Taiwan,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 years)
Secondary	PFS as Determined by the Investigator		From randomization to the first occurrence of disease progression or death from any cause (up to approximately 8 years)
Secondary	Complete Response Rate		Up to approximately 8 years
Secondary	Objective Response Rate (ORR)		Up to approximately 8 years
Secondary	Overall Survival (OS)		From randomization to death from any cause (up to approximately 8 years)
Secondary	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 years)
Secondary	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 years)
Secondary	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 years
Secondary	Time to Deterioration in Lymphoma Symptoms, as Measured by the Functional Assessment of Cancer Therapy-Lymphoma Subscale (FACT-LymS)		Up to approximately 8 years
Secondary	Percentage of Participants with Adverse Events (AEs)		Up to approximately 8 years
Secondary	Serum Concentration of M + Len		Up to approximately 8 years
Secondary	Area Under the Curve (AUC) of M + Len		Up to approximately 8 years
Secondary	Percentage of Participants with Anti-Drug Antibodies (ADAs)		Up to approximately 8 years
Secondary	Time to Next Anti-Lymphoma Treatment (TTNALT)		From randomization to the first documented administration of a new anti-lymphoma treatment (up to approximately 8 years)