Actively Recruiting
Phase II Study of Glofitamab With Venetoclax +/- Zanubrutinib in High-risk Mantle-cell Lymphoma
Led by The Lymphoma Academic Research Organisation · Updated on 2026-02-11
100
Participants Needed
16
Research Sites
366 weeks
Total Duration
On this page
Sponsors
T
The Lymphoma Academic Research Organisation
Lead Sponsor
B
BeiGene
Collaborating Sponsor
AI-Summary
What this Trial Is About
This open-label, multicenter, three cohorts, phase II study is designed to assess a combination of Zanubrutinib/Venetoclax/Glofitamab or Venetoclax/Glofitamab in high-risk subjects with either first line or R/R Mantle Cell Lymphoma (MCL). Three independent cohorts will be run: * Cohort A will include subjects with a primary refractory or progressive disease within 24 months from initiation of first line treatment (POD 24). * Cohort B will be open for subjects with R/R MCL and refractory or progressive to a BTK inhibitor given previously (\>24 months if first line). * Cohort C will only enrol newly diagnosed and untreated MCL subjects with very high-risk features.
CONDITIONS
Official Title
Phase II Study of Glofitamab With Venetoclax +/- Zanubrutinib in High-risk Mantle-cell Lymphoma
Who Can Participate
Eligibility Criteria
You may qualify if you...
- For Cohort A: Primary refractory or disease progression within 24 months from first-line treatment start, including prior BTK inhibitor or CAR-T cell therapy failure.
- For Cohort B: Relapsed/refractory MCL with progression or refractory to prior BTK inhibitor treatment; first progression must be more than 24 months from diagnosis.
- For Cohort C: Newly diagnosed, untreated MCL patients with very high-risk features, including at least two specific genetic or clinical risk factors.
- Age 18 to less than 80 years at consent.
- Signed informed consent prior to any study procedures.
- Histologically confirmed mantle cell lymphoma with specific markers and available diagnostic tissue.
- Measurable disease by CT scan or clinical examination.
- Stage II to IV disease.
- ECOG performance status 0, 1, or 2.
- Life expectancy over 3 months.
- Adequate kidney function (creatinine clearance over 30 mL/min).
- Adequate liver function within specified limits unless due to lymphoma.
- Women of childbearing potential must have negative pregnancy tests and agree to pregnancy prevention measures.
- Men of reproductive potential must agree to use effective contraception.
- Adequate bone marrow function with specified blood count levels.
- Covered by social security (France).
- Able to understand and speak an official country language or use a translator.
- SARS-CoV-2 vaccination status as per local guidelines.
- Willing to comply with hospitalization for first two Glofitamab doses and all study procedures.
- Prior adverse events from cancer therapy must be resolved to Grade 1 or lower (except hematological toxicities).
You will not qualify if you...
- Known CD20 negative status at diagnosis or relapse.
- For Cohorts A and B: Refractory to combined BTK inhibitor and Bcl-2 therapy.
- Previous treatment with bispecific antibodies targeting CD3 and CD20.
- Current or past central nervous system or meningeal lymphoma involvement.
- Use of other anti-cancer drugs within 30 days before study start, except allowed exceptions.
- Heart function below specified limits or significant cardiovascular disease.
- Severe anemia, neutropenia, or thrombocytopenia below defined thresholds.
- Major surgery within 28 days before screening.
- Need for certain anticoagulants.
- Use of moderate or strong CYP3A inhibitors or inducers.
- Recent live vaccines (except COVID vaccine).
- Known allergies or contraindications to study drugs or related compounds.
- G6DP deficiency.
- Severe reactions to prior similar treatments.
- Recent immunosuppressive medication use.
- Inability to swallow capsules or significant gastrointestinal issues.
- Severe bleeding disorders.
- History of certain CNS diseases or intracranial events unless stable.
- Active serious infections or known HIV infection.
- Positive hepatitis B or C infection unless controlled.
- Recent or active COVID-19 infection.
- Suspected or confirmed tuberculosis or chronic active Epstein-Barr virus infection.
- Life-threatening illnesses or conditions compromising safety or study outcomes.
- Active autoimmune diseases requiring treatment or certain immune conditions.
- History of progressive multifocal leukoencephalopathy.
- Active malignancy other than treated disease unless disease-free for 2+ years or specific exceptions.
- Pregnant, planning pregnancy, or breastfeeding women.
- Significant medical or psychiatric conditions interfering with participation.
- Severe lung diseases or history of interstitial lung disease.
- Known or suspected hemophagocytic lymphohistiocytosis unless lymphoma-related.
- Significant liver diseases or disorders affecting coagulation.
- Prior solid organ transplant.
- Legal or ethical restrictions on participation (e.g., under legal protection or detention).
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 16 locations
1
Az Sint-Jan Brugge - Oostende Av
Bruges, Belgium
Actively Recruiting
2
Institut Jules Bordet
Brussels, Belgium
Actively Recruiting
3
Chu de Liege
Liège, Belgium
Actively Recruiting
4
Chu Ucl Namur - Site Godinne
Yvoir, Belgium
Actively Recruiting
5
Aphp - Hopital Henri Mondor
Créteil, France
Actively Recruiting
6
Chu Dijon Bourgogne
Dijon, France
Actively Recruiting
7
Chu de Lille - Hopital Claude Huriez
Lille, France
Actively Recruiting
8
Institut Paoli Calmettes
Marseille, France
Actively Recruiting
9
Chu de Montpellier
Montpellier, France
Actively Recruiting
10
Chu de Nantes
Nantes, France
Actively Recruiting
11
Chu Lyon-Sud
Pierre-Bénite, France
Actively Recruiting
12
Chu de Reims - Hopital Robert Debre
Reims, France
Actively Recruiting
13
Chu Pontchaillou
Rennes, France
Actively Recruiting
14
Centre Henri Becquerel
Rouen, France
Actively Recruiting
15
Institut Curie
Saint-Cloud, France
Actively Recruiting
16
Institut de Cancerologie Strasbourg Europe
Strasbourg, France
Actively Recruiting
Research Team
J
Julie JULIE ASSEMAT
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
3
Not the Right Trial for You?
Explore thousands of other clinical trials that might be a better match.
Sign up to get personalized trial recommendations delivered to your inbox.
Already have an account? Log in here