Study of Mosunetuzumab Plus Lenalidomide Compared to Anti-CD20 Anti-body + Chemotherapy in Follicular Lymphoma FLIPI2-5

Last updated: October 8, 2024
Sponsor: The Lymphoma Academic Research Organisation
Overall Status: Active - Recruiting

Phase

3

Condition

Lymphoma

Follicular Lymphoma

Lymphoproliferative Disorders

Treatment

Prednisone

Rituximab

Mosunetuzumab

Clinical Study ID

NCT06284122
MorningLyte
  • Ages > 18
  • All Genders

Study Summary

This study is a phase III, randomized, open-label, international, multicenter, interventional trial, designed to compare the efficacy and safety of mosunetuzumab in combination with lenalidomide versus anti-CD20 monoclonal antibody (mAb) plus chemotherapy in patients with previously untreated FLIPI 2-5 follicular lymphoma.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Patient with histologically proven previously untreated CD20+ follicular lymphomagrade 1, 2, or 3a (including patient watched during up to 10 years after initialdiagnosis) as assessed by the investigators according to the World HealthOrganization (WHO) 2016 classification12, or classical follicular lymphoma accordingto the WHO 2022 classification13. Diagnostic tissue must be available for centralpathology review, exploratory endpoints and secondary data use. (Patients withabsolute lymphocyte count > 20 G/L must be discussed with the Sponsor beforescreening/inclusion).

  2. FLIPI 2-5.

  3. All Ann Arbor stages (including stage I if FLIPI ≥ 2).

  4. Must need treatment as evidenced by at least one of the following criteria:

  • Bulky disease defined as:

  • a nodal or extranodal mass/lesion > 7 cm in its largest diameter or,

  • involvement of at least 3 nodal or extranodal sites (each with a diametergreater than > 3 cm)

  • Presence of at least one of the following B symptoms:

  • fever (> 38°C) of unclear etiology

  • night sweats

  • weight loss greater than 10% within the prior 6 months

  • Symptomatic splenomegaly

  • Any compressive syndrome (for example, but not restricted to- ureteral,orbital, gastrointestinal)

  • Any one of the following cytopenias due to lymphoma:

  • hemoglobin < 10g/dL (6.25 mmol/L)

  • platelets <100 x 109/L, or

  • absolute neutrophil count (ANC) < 1.5 x 109/L

  • Pleural or peritoneal serous effusion (irrespective of cell content)

  • β2microglobulin > ULN or lactate dehydrogenase (LDH) > ULN

  1. At least one bi-dimensionally measurable nodal lesion, defined as > 1.5 cm in itslongest dimension, or at least one bi-dimensionally measurable extra nodal lesion,defined as > 1.0 cm in its longest dimension (and 18F-2-fluoro-2-deoxy-D-glucose (FDG)-avid lesion).

  2. Patient who understood and voluntarily signed and dated an informed consent prior toany study-specific assessments/procedures.

  3. Must be ≥ 18 years at the time of signing the informed consent form (ICF).

  4. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.

  5. Estimated minimum life expectancy of 3 months.

  6. Adequate hematological function within 28 days prior to signing informed consent,including:

  • Absolute neutrophil count (ANC) ≥ 1 x 109/L

  • Platelet count ≥ 75 x 109/L, or ≥ 30 x 109/L if bone marrow infiltration orsplenomegaly

  • Hemoglobin ≥ 8.0 g/dL (5 mmol/L) unless related to bone marrow infiltration orsplenomegaly. Transfusion is allowed before starting treatment (no requiredwindow)

  1. Normal laboratory values:
  • Measured or estimated creatinine clearance ≥ 40 mL/min calculated byinstitutional standard method (MDRD or Cockcroft-Gault)

  • aspartate aminotransferase (AST) or alanine aminotransférase (ALT) ≤ 2.5 x theupper limit of normal (ULN), except in patients with documented liver orpancreatic involvement by lymphoma ≤ 5 x ULN

  • Serum total bilirubin ≤ 1.5 x ULN (or ≤ 3 x ULN for patients with Gilbertsyndrome), except in patients with documented liver or pancreatic involvementby lymphoma ≤ 3 x ULN

  1. left ventricular ejection fraction (LVEF) within normal range (i.e. > 50% asevaluated by Transthoracic Echocardiography or > 45% as evaluated by isotopic method (MUGA scan)).

  2. Patients should be able to receive adequate prophylaxis and/or therapy forthromboembolic events (aspirin, low molecular weight heparin or direct oralanticoagulants). Patients with a curative anticoagulation therapy can be enrolled. A patient withdeep vein thrombosis due to compressive syndrome is eligible if a curativeanticoagulation therapy has been started at least 1 week before initiating studytreatment: low molecular weight heparin possible at treatment onset, then directoral anticoagulants according to local practices.

  3. Must be able to adhere to the study visit schedule and other protocol requirements.

  4. Negative SARS-CoV-2 test within 7 days prior to randomization. Rapid antigen test isalso acceptable. If a patient has a positive SARS-CoV-2 test before randomization,another test should be done and be negative within 7 days before initiation oftreatment.

  5. Negative HIV test before randomization, with the following exception: Patients with a positive HIV test before randomization are eligible provided theyare stable on antiretroviral therapy for at least 4 weeks, have a CD4 count ≥ 200/ µL, have an undetectable viral load, and have not had a history of opportunisticinfection attributable to AIDS within the last 12 months.

  6. For women of childbearing potential (WOCBP) (refer to section 14.7): must have anegative result for pregnancy test (highly sensitive serum) at screening and within 7 days before initiation of study treatment, and agree to abstain from breastfeedingduring study participation, and for at least 28 days after the final dose oflenalidomide (if applicable), 3 months after the final dose of mosunetuzumab andtocilizumab (if applicable), 6 months after the final dose of chemotherapies (ifapplicable), 12 months after the final dose of rituximab (if applicable), and 18months after the final dose of obinutuzumab (if applicable).

  7. For men (refer to section 14.7): Agreement to remain abstinent (refrain fromheterosexual intercourse) or use a condom, and agreement to refrain from donatingsperm, as defined below: with a female partner of childbearing potential or pregnantfemale partner, men must remain abstinent or use a condom during the treatmentperiod (including periods of treatment interruption), and for at least 28 days afterthe final dose of lenalidomide (if applicable), 2 months after the final dose oftocilizumab (if applicable), 6 months after the final dose of chemotherapies (ifapplicable), 12 months after the final dose of rituximab (if applicable), and 3months after the final dose of obinutuzumab (if applicable).

  8. Patient covered by any social security system (France).

  9. Patient who understands and speaks one of the country official languages, unlesslocal regulation authorizes independent translators.

Exclusion

Exclusion Criteria:

  1. Grade 3b follicular lymphoma according to the WHO 2016 classification12, orfollicular large B-cell lymphoma according to the WHO 2022 classification13.

  2. Suspicion or clinical evidence of transformed lymphoma at enrollment by investigatorassessment (e.g., high SUV in at least one lesion that was not biopsied, anddiscordant with SUV of biopsied lesion (at least double of the average SUV), LDH > 2.5 x ULN especially in a context of rapidly progressive disease, etc. (Pleasecontact the Sponsor to discuss any possible inclusion in borderline cases or anydoubt)

  3. Prior localized radiotherapy for the FL.

  4. Prior history of another lymphoma.

  5. Uncontrolled symptomatic pleural or serous effusion requiring urgent treatmentwithin 48 hours (patients with controlled disease after adequate pleural/serousdrainage and/or effective pleurX™ or similar system are eligible).

  6. Uncontrolled symptomatic ureterohydronephrosis resulting in renal failure (patientswith adequate management i.e. ureteral catheter or double J stent allowing renalfailure control are eligible).

  7. Symptomatic lymphomatous epidural lesion (patients whose disease is controlled byneurosurgery or short course of steroids are eligible).

  8. Use of any standard or experimental anti-cancer drug therapy within 42 days of thestart (Day 1) of study treatment.

  9. Systemic immunosuppressive medications (including, but not limited to,cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosisfactor agents) or corticosteroid > 1mg/kg/day prednisone or equivalent within 10days prior to first dose of study treatment. Systemic corticosteroid treatment < 20mg/day of prednisone or equivalent, inhaled corticosteroids and mineralocorticoidsfor management of orthostatic hypotension is permitted. A single dose ofdexamethasone for nausea or B symptoms is permitted.

  10. Received a live, attenuated vaccine within 4 weeks before the first dose of studytreatment, or in whom it is anticipated that such a live attenuated vaccine will berequired during the study period or within 5 months after the final dose of studytreatment.

  11. Major surgery (excluding surgical documentation of FL) within 28 days prior tosigning informed consent.

  12. Seropositive for or active viral infection with Hepatitis B virus (HBV):

  • HBsAg positive

  • HBsAg negative, anti-HBs positive and/or anti-HBc positive and detectable viralDNA (Patients who are HBsAg negative, anti-HBs positive and/or anti-HBcpositive but viral DNA negative are eligible. They should be treated andperform testing at regular interval; Patients who are seropositive due to ahistory of hepatitis B vaccine (anti-HBs positive) are eligible).

  1. Known seropositive for, or active infection hepatitis C virus (HCV) (Patients whoare positive for HCV antibody with a negative viral RNA are eligible).

  2. Known or suspected hypersensitivity to biopharmaceuticals produced in Chinesehamster ovarian (CHO) cells or any component of the mosunetuzumab, Anti-CD20 mAb,tocilizumab, lenalidomide formulation, including mannitol; or to any of theexcipients.

  3. History of solid organ transplantation or allogeneic stem cell transplant (SCT).

  4. Active autoimmune disease requiring treatment.

  5. History of autoimmune disease, including, but not limited to, myasthenia gravis,myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis,inflammatory bowel disease, vascular thrombosis associated with antiphospholipidsyndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome,multiple sclerosis, vasculitis, or glomerulonephritis

  • Participants with a history of autoimmune-related hypothyroidism on a stabledose of thyroid replacement hormone may be eligible.

  • Participants with controlled Type 1 diabetes mellitus who are on an insulinregimen are eligible for the study.

  • Participants with a history of disease-related immune thrombocytopenic purpuraor autoimmune hemolytic anemia may be eligible.

  • Participants with a remote history of, or well-controlled autoimmune disease,with a treatment-free interval from immunosuppressive therapy for 12 months maybe eligible after review and discussion with the Primary investigator.

  1. Participants with any active infection such as known active bacterial, viral (including SARS-CoV-2), fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds), known or suspected chronic activeEpstein-Barr virus (EBV) infection, are excluded.

  2. Evidence of any significant, concomitant disease that could affect compliance withthe protocol or interpretation of results, including, but not limited to:

  • significant cardiovascular disease [e.g., Objective Class C or D heart diseases (cf. Classes of Heart Failure | American Heart Association), myocardialinfarction within the previous 6 months, unstable arrhythmia, or unstableangina)

  • significant pulmonary disease (such as obstructive pulmonary disease or historyof bronchospasm)

  • clinically significant history of liver disease, including viral or otherhepatitis, or cirrhosis

  • current or past history of central nervous system (CNS) disease, such asstroke, epilepsy, CNS vasculitis, or neurodegenerative disease. Participantswith a history of stroke who have not experienced a stroke or transientischemic attack in the past 1 year and have no residual neurologic deficits asjudged by the investigator are allowed. Participants with a history of epilepsywho have had no seizures in the past 2 years with or without anti-epilepticmedications can be eligible.

  1. History of confirmed progressive multifocal leukoencephalopathy (PML).

  2. Known or suspected history of hemophagocytic lymphohistiocytosis (HLH).

  3. History of erythema multiforme, Grade ≥3 rash, or blistering rash following priortreatment with immunomodulatory derivatives.

  4. History of interstitial lung disease (ILD), drug-induced pneumonitis, and autoimmunepneumonitis.

  5. Active malignancy other than the one treated in this research. Prior history ofmalignancies unless the patient has been free of the disease for ≥ 3 years. However,patients with the following history/concurrent conditions are eligible:

  • Localized non-melanoma skin cancer.

  • Carcinoma in situ of the cervix.

  • Carcinoma in situ of the breast.

  • Incidental histologic finding of prostate cancer (T1a or T1b as per Tumor NodeMetastasis (TNM) staging system) or prostate cancer that has been treated withcurative intent.

  1. Presence or history of CNS or meningeal involvement by lymphoma.

  2. Pregnant, planning to become pregnant or lactating WOCBP.

  3. Any significant medical conditions, including the presence of laboratory abnormalityor psychiatric illness which places the patient at unacceptable risk if he/she wereto participate in the study, and likely to interfere with participation in thisclinical study (according to the investigator's decision) or which confounds theability to interpret data from the study.

  4. Person deprived of his/her liberty by a judicial or administrative decision.

  5. Person hospitalized without consent.

  6. Adult person under legal protection.

Nota bene: for 28., if there is an individual benefit for such patients, an Ethics Committee will have to be informed case by case.

Study Design

Total Participants: 790
Treatment Group(s): 9
Primary Treatment: Prednisone
Phase: 3
Study Start date:
June 07, 2024
Estimated Completion Date:
April 30, 2034

Study Description

This study is a phase III, randomized, open-label, international, multicenter, interventional trial, designed to compare the efficacy and safety of mosunetuzumab in combination with lenalidomide versus anti-CD20 monoclonal antibody (mAb) plus chemotherapy in patients with previously untreated Follicular Lymphoma International Prognostic Index (FLIPI) 2-5 follicular lymphoma This study is composed of a screening period (up to 6 weeks before randomization, i.e., 42 days), a treatment period (30 months i.e., 125w), a safety follow-up period (90 days i.e., 3 months), and a survival follow-up period (up to 7 years after the last randomized patient). The enrollment will last approximately 34 months. The total duration of the study will be therefore approximately 10 years.

Once a patient provides written consent, they may enter the screening phase, with a duration up to 6 weeks prior to randomization and initiation of treatment.

Upon completion of the required assessments in the screening phase, and fulfillment of the eligibility criteria, patients will be randomized. Investigators will be requested to indicate their treatment choice among permitted immuno-chemotherapy regimens just before randomization.

The treatment period for each patient starts with the first intake. The patients will receive protocol-specified treatments until:

  • inability to achieve a response at the end of induction phase (at M12 evaluation for experimental arm, and at M6 evaluation for control arms),

  • relapse or progression of the disease,

  • withdrawal of consent,

  • or unacceptable toxicity

In the experimental arm, patients will be treated for 1 cycle of 3 weeks for mosunetuzumab and then 11 cycles of 4 weeks for mosunetuzumab and lenalidomide (47 weeks, around 11 months) during the induction phase, and for a maximum of 9 additional cycles of 8 weeks during the maintenance phase (72 weeks, around 17 months), up to around 125 weeks (30 months). Patients should start the maintenance phase 7 to 8 weeks after the start of last induction cycle (C12).

In the control arm, patients will be treated for 8 or 6 cycles of 3 or 4 weeks for anti-CD20 mAb +cyclophosphamide-doxorubicine-vincristine-prednisone (CHOP) or anti-CD20 mAb + Bendamustine, respectively, depending on the assigned arm (24 weeks, around 5 months) during the induction phase, and for a maximum of 12 additional cycles of 8 weeks during the maintenance phase (96 weeks, around 22 months), up to around 125 weeks (30 months). Patients should start the maintenance phase, 6 to 7 or 7 to 8 weeks after the start of last induction cycle (C8 or C6).

The option to cross-over from the control arm to the experimental arm is not allowed.

All randomized patients will be followed for progression-free survival and overall survival using the same schedule. Patients will be followed up from End of treatment evaluation every 3 months during the first two years, then every 6 months during the next 3 years, then yearly until the end of study.

The end of study will occur when all randomized patients have been followed-up for survival for at least 7 years (or discontinued study early).

Connect with a study center

  • AZ SINT-JAN BRUGGE - OOSTENDE AV - Service Hématologie

    Brugge, 8000
    Belgium

    Active - Recruiting

  • INSTITUT JULES BORDET - Service Hématologie

    Bruxelles, 1070
    Belgium

    Active - Recruiting

  • UNIVERSITE CATHOLIQUE DE LOUVAIN SAINT-LUC - Service Hématologie

    Bruxelles, 1200
    Belgium

    Active - Recruiting

  • GRAND HOPITAL DE CHARLEROI - Service Hématologie

    Charleroi, 6000
    Belgium

    Active - Recruiting

  • UNIVERSITAIR ZIEKENHUIS GENT - Service Hématologie

    Gent, 9000
    Belgium

    Active - Recruiting

  • CHU DE LIEGE - Service Hématologie

    Liège, 4000
    Belgium

    Active - Recruiting

  • CHR VERVIERS - LA TOURELLE - Service Hématologie

    Verviers, 4800
    Belgium

    Active - Recruiting

  • CHU UCL NAMUR - SITE GODINNE - Service Hématologie

    Yvoir, 5530
    Belgium

    Active - Recruiting

  • CH d'AVIGNON - HOPITAL HENRI DUFFAUT - Service d'Onco-Hématologie

    Avignon, 84000
    France

    Active - Recruiting

  • CH DE LA COTE BASQUE - Service Hématologie

    Bayonne, 64100
    France

    Active - Recruiting

  • CHU JEAN MINJOZ - Service Hématologie

    Besançon, 25030
    France

    Active - Recruiting

  • INSTITUT BERGONIE - Service d'Oncologie Médicale

    Bordeaux, 33076
    France

    Active - Recruiting

  • CENTRE HOSPITALIER JEAN ROUGIER - Service d'Oncologie - Hématologie

    Cahors, 46005
    France

    Active - Recruiting

  • CH METROPOLE SAVOIE - SITE CHAMBERY - Service Hématologie

    Chambéry, 73011
    France

    Active - Recruiting

  • CHU ESTAING - Service Thérapie Cellulaire et Hématologie Clinique

    Clermont-Ferrand, 63003
    France

    Active - Recruiting

  • HOPITAL HENRI MONDOR - Unité Hémopathies Lymphoïdes

    Créteil, 94010
    France

    Active - Recruiting

  • CHU DIJON BOURGOGNE - Service Hématologie Clinique

    Dijon, 21000
    France

    Active - Recruiting

  • CHD DE VENDEE - Service Hématologie

    La Roche-sur-Yon, 85925
    France

    Active - Recruiting

  • CHU DE GRENOBLE - Service Hématologie

    La Tronche, 38700
    France

    Active - Recruiting

  • CHRU DE LILLE - HOPITAL CLAUDE HURIEZ - Service Hématologie

    Lille, 59037
    France

    Active - Recruiting

  • HOPITAL SAINT VINCENT-DE-PAUL - Service Hématologie

    Lille, 59020
    France

    Active - Recruiting

  • CHU DE LIMOGES - HOPITAL DUPUYTREN - Service Hématologie Clinique et Thérapie Cellulaire

    Limoges, 87042
    France

    Active - Recruiting

  • INSTITUT PAOLI CALMETTES - Service Hématologie

    Marseille, 13273
    France

    Active - Recruiting

  • CHU DE MONTPELLIER - Département d'Hématologie Clinique

    Montpellier, 34090
    France

    Active - Recruiting

  • GH REGION MULHOUSE ET SUD ALSACE - HOPITAL EMILE MULLER - Service Hématologie

    Mulhouse, 68100
    France

    Active - Recruiting

  • CHU DE NANTES - Service Hématologie

    Nantes, 44093
    France

    Active - Recruiting

  • CENTRE HOSPITALIER DE NIORT - Médecine interne

    Niort, 79021
    France

    Active - Recruiting

  • HOPITAL SAINT-LOUIS - Service Hématologie

    Paris, 75475
    France

    Active - Recruiting

  • CHU DE BORDEAUX - HOPITAL HAUT-LEVEQUE - CENTRE FRANCOIS MAGENDIE - Service d'Hématologie et Thérapie Cellulaire

    Pessac, 33604
    France

    Active - Recruiting

  • CHU LYON-SUD - Hématologie

    Pierre-Bénite, 69495
    France

    Active - Recruiting

  • CHI POISSY SAINT-GERMAIN-EN-LAYE - Service Hématologie

    Poissy, 78303
    France

    Active - Recruiting

  • CHU DE POITIERS - HOPITAL DE LA MILETRIE - Service d'Oncologie Hématologique et Thérapie Cellulaire

    Poitiers, 86021
    France

    Active - Recruiting

  • CH ANNECY GENEVOIS - SITE D'ANNECY - Service Hématologie

    Pringy, 74374
    France

    Active - Recruiting

  • CHU DE REIMS - HOPITAL ROBERT DEBRE - Service Hématologie

    Reims, 57092
    France

    Active - Recruiting

  • CHU PONTCHAILLOU - Hématologie Clinique

    Rennes, 35033
    France

    Active - Recruiting

  • CENTRE HENRI BECQUEREL - Service Hématologie

    Rouen, 76038
    France

    Active - Recruiting

  • INSTITUT CURIE - SITE SAINT-CLOUD - Service Hématologie

    Saint-Cloud, 92210
    France

    Active - Recruiting

  • Institut de Cancérologie et d'Hématologie Universitaire de Saint-Étienne - Service Hématologie

    Saint-Priest-en-Jarez, 42270
    France

    Active - Recruiting

  • INSTITUT DE CANCEROLOGIE STRASBOURG EUROPE - Unité de Recherche Clinique

    Strasbourg, 67033
    France

    Active - Recruiting

  • IUCT ONCOPOLE - Service Hématologie

    Toulouse, 31059
    France

    Active - Recruiting

  • CHU BRETONNEAU - Service Cancérologie - Hématologie et Thérapie Cellulaire

    Tours, 37044
    France

    Active - Recruiting

  • CH DE VALENCIENNES - HOPITAL JEAN BERNARD - Service Hématologie

    Valenciennes, 59322
    France

    Active - Recruiting

  • CHU BRABOIS - Service Hématologie

    Vandœuvre-lès-Nancy, 54511
    France

    Active - Recruiting

  • CH DE BRETAGNE ATLANTIQUE - HOPITAL CHUBERT - Service Hématologie

    Vannes, 56017
    France

    Active - Recruiting

  • GUSTAVE ROUSSY CANCER CAMPUS GRAND PARIS - Département Médecine Oncologique

    Villejuif, 94085
    France

    Active - Recruiting

  • UNIVERSITATSKLINIKUM REGENSBURG - Klinik für Innere Medizin III

    Regensburg, 93053
    Germany

    Active - Recruiting

  • UNIV KLINIKUM ULM - INNERE MEDIZIN III - Service Hématologie

    Ulm, 89081
    Germany

    Active - Recruiting

  • INSTITUTO PORTUGUES DE ONCOLOGIA DE LISBOA FRANCISCO GENTIL - Departamento Hematologia

    Lisboa, 1099
    Portugal

    Active - Recruiting

  • HOSPITAL CLINICO SALAMANCA - Servicio de Hematologia

    Salamanca, 37007
    Spain

    Active - Recruiting

Not the study for you?

Let us help you find the best match. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.