Informations générales (source: ClinicalTrials.gov)
A Phase III Randomized, Open-label, International, Multicenter Study Evaluating the Efficacy and Safety of Mosunetuzumab Plus Lenalidomide in Comparison to Anti-CD20 Monoclonal Antibody Plus Chemotherapy in Subjects With Previously Untreated FLIPI 2-5 Follicular Lymphoma
Interventional
Phase 3
The Lymphoma Academic Research Organisation (Voir sur ClinicalTrials)
juin 2024
avril 2034
07 juin 2026
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.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC RENE HUGUENIN INSTITUT CURIE | 10/04/2025 13:11:55 | Contact (sur clinicalTrials) | |||
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| AP-HP - Hôpital Henri Mondor-Albert Chenevier | François LEMONNIER, MD | Contact (sur clinicalTrials) | |||
| CLCC INSTITUT GUSTAVE ROUSSY | Vincent RIBRAG, MD | Contact (sur clinicalTrials) | |||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| CENTRE HENRI BECQUEREL - Service Hématologie - 76038 - Rouen - France | Fabrice JARDIN, Pr | Contact (sur clinicalTrials) | |||
| CENTRE HOSPITALIER DE NIORT - Médecine interne - 79021 - Niort - France | Gaëlle OLIVIER, MD | Contact (sur clinicalTrials) | |||
| CENTRE HOSPITALIER JEAN ROUGIER - Service d'Oncologie - Hématologie - 46005 - Cahors - France | Martin GAUTHIER, MD | Contact (sur clinicalTrials) | |||
| CH ANNECY GENEVOIS - SITE D'ANNECY - Service Hématologie - 74374 - Pringy - France | Hannah MOATTI, MD | Contact (sur clinicalTrials) | |||
| CH d'AVIGNON - HOPITAL HENRI DUFFAUT - Service d'Onco-Hématologie - 84000 - Avignon - France | Hacène ZERAZHI, MD | Contact (sur clinicalTrials) | |||
| CH DE BRETAGNE ATLANTIQUE - HOPITAL CHUBERT - Service Hématologie - 56017 - Vannes - France | Antoine BONNET, MD | Contact (sur clinicalTrials) | |||
| CH DE LA COTE BASQUE - Service Hématologie - 64100 - Bayonne - France | Sophie BERNARD, MD | Contact (sur clinicalTrials) | |||
| CH DE VALENCIENNES - HOPITAL JEAN BERNARD - Service Hématologie - 59322 - Valenciennes - France | Sabine TRICOT, MD | Contact (sur clinicalTrials) | |||
| CH METROPOLE SAVOIE - SITE CHAMBERY - Service Hématologie - 73011 - Chambéry - France | Arthur DONY, MD | Contact (sur clinicalTrials) | |||
| CHD DE VENDEE - Service Hématologie - 85925 - La Roche-sur-Yon - France | Nadine MORINEAU, MD | Contact (sur clinicalTrials) | |||
| CHI POISSY SAINT-GERMAIN-EN-LAYE - Service Hématologie - 78303 - Poissy - France | Mohammed BOUDERBALA, MD | Contact (sur clinicalTrials) | |||
| CHRU DE LILLE - HOPITAL CLAUDE HURIEZ - Service Hématologie - 59037 - Lille - France | Franck MORSCHHAUSER, Pr | Contact (sur clinicalTrials) | |||
| CHU BRABOIS - Service Hématologie - 54511 - Vandœuvre-lès-Nancy - France | Pierre FEUGIER, Pr | Contact (sur clinicalTrials) | |||
| CHU BRETONNEAU - Service Cancérologie - Hématologie et Thérapie Cellulaire - 37044 - Tours - France | Laurianne DRIEU LA ROCHELLE, MD | Contact (sur clinicalTrials) | |||
| CHU DE BORDEAUX - HOPITAL HAUT-LEVEQUE - CENTRE FRANCOIS MAGENDIE - Service d'Hématologie et Thérapie Cellulaire - 33604 - Pessac - France | François-Xavier GROS, MD | Contact (sur clinicalTrials) | |||
| CHU DE GRENOBLE - Service Hématologie - 38700 - La Tronche - France | Sylvain CARRAS, MD | Contact (sur clinicalTrials) | |||
| CHU DE LIMOGES - HOPITAL DUPUYTREN - Service Hématologie Clinique et Thérapie Cellulaire - 87042 - Limoges - France | Julie ABRAHAM, MD | Contact (sur clinicalTrials) | |||
| CHU DE MONTPELLIER - Département d'Hématologie Clinique - 34090 - Montpellier - France | Guillaume CARTRON, Pr | Contact (sur clinicalTrials) | |||
| CHU DE NANTES - Service Hématologie - 44093 - Nantes - France | Thomas GASTINNE, MD | Contact (sur clinicalTrials) | |||
| CHU DE POITIERS - HOPITAL DE LA MILETRIE - Service d'Oncologie Hématologique et Thérapie Cellulaire - 86021 - Poitiers - France | Stéphanie GUIDEZ, MD | Contact (sur clinicalTrials) | |||
| CHU DE REIMS - HOPITAL ROBERT DEBRE - Service Hématologie - 57092 - Reims - France | Eric DUROT, MD | Contact (sur clinicalTrials) | |||
| CHU DIJON BOURGOGNE - Service Hématologie Clinique - 21000 - Dijon - France | Amandine DURAND, MD | Contact (sur clinicalTrials) | |||
| CHU ESTAING - Service Thérapie Cellulaire et Hématologie Clinique - 63003 - Clermont-Ferrand - France | Romain GUIEZE, Pr | Contact (sur clinicalTrials) | |||
| CHU JEAN MINJOZ - Service Hématologie - 25030 - Besançon - France | Adrien CHAUCHET, MD | Contact (sur clinicalTrials) | |||
| CHU LYON-SUD - Hématologie - 69495 - Pierre-Bénite - France | Emmanuel BACHY, Pr | Contact (sur clinicalTrials) | |||
| CHU PONTCHAILLOU - Hématologie Clinique - 35033 - Rennes - France | Roch HOUOT, Pr | Contact (sur clinicalTrials) | |||
| GH REGION MULHOUSE ET SUD ALSACE - HOPITAL EMILE MULLER - Service Hématologie - 68100 - Mulhouse - France | Bernard DRENOU, MD | Contact (sur clinicalTrials) | |||
| HOPITAL SAINT VINCENT-DE-PAUL - Service Hématologie - 59020 - Lille - France | Sandy AMORIM, MD | Contact (sur clinicalTrials) | |||
| HOPITAL SAINT-LOUIS - Service Hématologie - 75475 - Paris - France | Catherine THIEBLEMONT, Pr | Contact (sur clinicalTrials) | |||
| INSTITUT BERGONIE - Service d'Oncologie Médicale - 33076 - Bordeaux - France | Fontanet BIJOU, MD | Contact (sur clinicalTrials) | |||
| Institut de Cancérologie et d'Hématologie Universitaire de Saint-Étienne - Service Hématologie - 42270 - Saint-Priest-en-Jarez - France | Ludovic FOUILLET, MD | Contact (sur clinicalTrials) | |||
| INSTITUT DE CANCEROLOGIE STRASBOURG EUROPE - Unité de Recherche Clinique - 67033 - Strasbourg - France | Luc-Matthieu FORNECKER, Pr | Contact (sur clinicalTrials) | |||
| INSTITUT PAOLI CALMETTES - Service Hématologie - 13273 - Marseille - France | Gabriel BRISOU, MD | Contact (sur clinicalTrials) | |||
| IUCT ONCOPOLE - Service Hématologie - 31059 - Toulouse - France | Loïc YSEBAERT, MD | Contact (sur clinicalTrials) | |||
Critères
Tous
1. 1. Patient with histologically proven previously untreated CD20+ follicular lymphoma
grade 1, 2, or 3a (including patient watched during up to 10 years after initial
diagnosis) as assessed by the investigators according to the WHO 2016
classification12, or classical follicular lymphoma according to the WHO 2022
classification13. Diagnostic tissue must be available for central pathology review,
exploratory endpoints and secondary data use.
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:
4.1. Bulky disease defined as one of the following: 4.1.1. a nodal or extranodal
mass/lesion > 70 mm in its largest diameter or, 4.1.2. involvement of at least 3
different nodal or extranodal sites (each with a diameter greater than > 30 mm) 4.2.
Presence of at least one of the following B symptoms within the prior 6 months:
4.2.1. fever (> 38°C) of unclear etiology 4.2.2. night sweats 4.2.3. weight loss
greater than 10% 4.3. Symptomatic splenomegaly 4.4. Symptomatic lesion: 4.4.1.
painful lesion and/or 4.4.2. any compressive syndrome (for example, but not
restricted to- ureteral, orbital, gastrointestinal) 4.5. Any one of the following
cytopenias due to lymphoma: 4.5.1. hemoglobin < 10g/dL (6.25 mmol/L) 4.5.2.
platelets <100 x 109/L, or 4.5.3. absolute neutrophil count (ANC) < 1.5 x 109/L 4.6.
Pleural or peritoneal serous effusion (irrespective of cell content) 4.7. Abnormal
biological prognostic parameters: (item not applicable for Germany) 4.7.1.
β2microglobulin > ULN or 4.7.2. LDH > ULN
5. At least one bi-dimensionally measurable nodal lesion, defined as > 15 mm in its
longest dimension, or at least one bi-dimensionally measurable extra nodal lesion,
defined as > 10 mm in its longest dimension (and FDG-avid lesion).
6. Participant who understood and voluntarily signed and dated an informed consent
prior to any study-specific assessments/procedures.
7. Must be ≥ 18 years old at the time of signing the informed consent form (ICF).
8. ECOG performance status 0 to 2.
9. Estimated minimum life expectancy of 3 months.
10. Adequate hematological function within 28 days prior to randomization, including:
10.1. Absolute neutrophil count (ANC) ≥ 1 x 109/L 10.2. Platelet count ≥ 75 x 109/L,
or ≥ 30 x 109/L if bone marrow infiltration or splenomegaly 10.3. Hemoglobin ≥ 8.0
g/dL (5 mmol/L) unless related to bone marrow infiltration or splenomegaly.
Transfusion is allowed before starting treatment (no required window)
11. Normal laboratory values:
11.1. Measured or estimated creatinine clearance ≥ 40mL/min calculated by
institutional standard method (MDRD or Cockcroft-Gault 11.2. AST or ALT ≤ 2.5 x the
upper limit of normal (ULN), except in patients with documented liver or pancreatic
involvement by lymphoma ≤ 5 x ULN 11.3. Serum total bilirubin ≤ 1.5 x ULN (or ≤ 3 x
ULN for patients with Gilbert syndrome), except in patients with documented liver or
pancreatic involvement by lymphoma ≤ 3 x ULN
12. LVEF within normal range (i.e. > 50% as evaluated by Transthoracic Echocardiography
or > 45% as evaluated by isotopic method (MUGA scan).
13. Participants should be able to receive adequate prophylaxis and/or therapy for
thromboembolic events (aspirin, low molecular weight heparin or direct oral
anticoagulants).
Patients with a curative anticoagulation therapy can be enrolled. A patient with
deep vein thrombosis due to compressive syndrome is eligible if a curative
anticoagulation therapy has been started at least 1 week before initiating study
treatment: low molecular weight heparin possible at treatment onset, then direct
oral anticoagulants according to local practices.
14. Must be able to adhere to the study visit schedule and other protocol requirements.
15. No more applicable following SM#14
16. Negative HIV test before randomization, with the following exception:
Patients with a positive HIV test before randomization are eligible provided they
are stable on antiretroviral therapy for at least 4 weeks, have a CD4 count ≥
200/uL, have an undetectable viral load, and have not had a history of opportunistic
infection attributable to AIDS within the last 12 months.
17. For women of childbearing potential (WOCBP) :
- must have a negative result for pregnancy test (highly sensitive serum) within
7 days before randomization and within 7 days before initiation of study
treatment.
- must agree to abstain from becoming pregnant or breastfeeding, and agree to use
highly effective contraceptive methods during study participation, and for at
least 28 days after the final dose of lenalidomide (if applicable), 3 months
after the final dose of mosunetuzumab and tocilizumab (if applicable), 12
months after the final dose of CHOP (if applicable), 6 months after the final
dose of bendamustine (if applicable), 12 months after the final dose of
rituximab (if applicable), and 18 months after the final dose of obinutuzumab
(if applicable).
18. For men with a female partner of childbearing potential or pregnant female partner,
men must remain abstinent or use a condom during the treatment period (including
periods of treatment interruption), and for at least 07 days after the final dose of
lenalidomide (if applicable), 2 months after the final dose of tocilizumab (if
applicable), 6 months after the final dose of CHOP (if applicable), 3 months after
the final dose of bendamustine (if applicable), 12 months after the final dose of
rituximab (if applicable), and 3 months after the final dose of obinutuzumab (if
applicable). Men must also agree to refrain from donating sperm from the first day
of treatment until at least 7 days after the final dose of lenalidomide (if
applicable), 2 months after the final dose of tocilizumab (if applicable), 6 months
after the final dose of CHOP (if applicable), 3 months after the final dose of
bendamustine (if applicable), 12 months after the final dose of rituximab (if
applicable), and 3 months after the last dose of obinutuzumab (if applicable).
19. Participant covered by any social security system (France).
20. Participant who understands and speaks one of the country official languages, unless
local regulation authorizes independent translators.
Exclusion criteria:
1. Grade 3b follicular lymphoma according to the WHO 2016 classification12, or
follicular large B-cell lymphoma according to the WHO 2022 classification13
2. Suspicion or clinical evidence of transformed lymphoma at enrollment by investigator
assessment.
Examples: patients with high or intermediate high SUV (>20) in any nodal or
extranodal site particularly in the bones (vertebrae etc) unless biopsy proven to be
genuine FL grade 1,2, 3A ; and/or discordant (e.g. SUV doubled) with SUV of other
sites including the biopsy site.; and/or LDH > 2.5 x ULN in a context of rapidly
progressive disease, etc. Please contact the Coordinating Investigator / Sponsor to
discuss such cases or if there is any doubt before considering enrolment.
3. Prior localized radiotherapy for the FL.
4. Prior history of another lymphoma.
5. Uncontrolled symptomatic pleural or serous effusion requiring urgent treatment
(within one week of finding). Participants may only be enrolled after Coordinating
investigator / sponsor approval once confirmed participant is durably asymptomatic
after adequate pleural/serous drainage or only if an efficient drainage device
(e.g.pleurX™) is in place before randomization.
6. Uncontrolled symptomatic ureterohydronephrosis resulting in renal failure.
Participants with adequate management i.e. ureteral catheter or double J stent
allowing renal failure control are eligible only if urinary catheter is in place
before randomization.
7. Presence or history of symptomatic or threatening lymphomatous epidural/nerve root
lesion, even such participants whose disease is controlled by short course of
steroids are NOT eligible.
8. Use of any standard or experimental anti-cancer drug therapy within 45 days of the
start (Day 1) of study treatment.
9. Any contraindication to any drug contained in the study treatment control arms or in
the Auxiliary Medicinal Products (AxMPs)
10. Systemic immunosuppressive medications (including, but not limited to,
cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis
factor agents) and corticosteroids on the long run with the following exceptions:
inhaled steroids for asthma, topical steroids, or replacement or stress
corticosteroids during the study at any time. Participants who require lymphoma
symptom control during screening may receive corticosteroid < or = 1mg/kg/day
prednisone or equivalent for a maximum of 10 days prior to first dose of study
treatment
11. Received a live, attenuated vaccine within 4 weeks before the first dose of study
treatment, or in whom it is anticipated that such a live attenuated vaccine will be
required during the study period or within 6 months after the final dose of study
treatment.
12. Major surgery (excluding surgical documentation of FL) within 28 days prior to
signing informed consent.
13. 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 viral
DNA (Patients who are HBsAg negative, anti-HBs positive and/or anti-HBc
positive but viral DNA negative are eligible. They should be treated and
perform testing at regular interval described in section Anti infectious
prophylaxis; Patients who are seropositive due to a history of hepatitis B
vaccine (anti-HBs positive) are eligible).
14. Known seropositive for, or active infection hepatitis C virus (HCV) (Patients who
are positive for HCV antibody with a negative viral RNA are eligible).
15. Known or suspected hypersensitivity to biopharmaceuticals produced in CHO cells or
any component of the mosunetuzumab, anti-CD20 mAb, tocilizumab, lenalidomide
formulation, including mannitol; or to any of the excipients.
16. History of solid organ transplantation or allogeneic stem cell transplant (SCT).
17. Active autoimmune disease requiring treatment.
18. 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 antiphospholipid
syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome,
multiple sclerosis, vasculitis, uveitis, or glomerulonephritis.
- Participants with a history of autoimmune-related hypothyroidism on a stable
dose of thyroid replacement hormone may be eligible.
- Participants with controlled Type 1 diabetes mellitus who are on an insulin
regimen are eligible for the study.
- Participants with a remote history of, or well-controlled autoimmune disease,
with a treatment-free interval from immunosuppressive therapy for 12 months may
be eligible after review and discussion with the Coordinating investigator.
19. 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 active
Epstein-Barr virus (EBV) infection are excluded.
20. Evidence of any significant, concomitant disease that could affect compliance with
the 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), myocardial
infarction within the previous 6 months, unstable arrhythmia, or unstable
angina)
- significant pulmonary disease (such as obstructive pulmonary disease or history
of bronchospasm)
- clinically significant history of liver disease, including viral or other
hepatitis, or cirrhosis
- current or past history of central nervous system (CNS) disease, such as
stroke, epilepsy, CNS vasculitis, or neurodegenerative disease. Participants
with a history of stroke who have not experienced a stroke or transient
ischemic attack in the past 1 year and have no residual neurologic deficits as
judged by the investigator are allowed. Participants with a history of epilepsy
who have had no seizures in the past 2 years with or without anti-epileptic
medications can be eligible.
21. History of confirmed progressive multifocal leukoencephalopathy (PML).
22. Known or suspected history of hemophagocytic lymphohistiocytosis (HLH).
23. History of erythema multiforme, Grade ≥3 rash, or blistering rash following prior
treatment with immunomodulatory derivatives.
24. History of interstitial lung disease (ILD), drug-induced pneumonitis, and autoimmune
pneumonitis.
25. Active malignancy other than the one treated in this research. Prior history of
malignancies unless the patient has been free of the disease and therapy for ≥ 3
years. However, patients with a single occurrence of the following conditions that
have been treated with curative intent 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 Node
Metastasis [TNM] staging system) or prostate cancer.
26. Presence or history of CNS or meningeal involvement by lymphoma.
27. Pregnant, planning to become pregnant or lactating WOCBP.
28. Any significant medical conditions, including the presence of laboratory abnormality
or psychiatric illness which places the patient at unacceptable risk if he/she were
to participate in the study, and likely to interfere with participation in this
clinical study (according to the investigator's decision) or which confounds the
ability to interpret data from the study.
29. Person deprived of his/her liberty by a judicial or administrative decision.
30. Person hospitalized without consent.
31. Adult person under legal protection.
32. Patients with absolute lymphocyte count > 20 G/L before randomization. Participants
circulating lymphoma cell≥ 5 G/L must be discussed with the Sponsor before
randomization.
NB: for 29-31., if there is an individual benefit for such patients, an Ethics Committee
will have to be informed case by case.