Study of Ibrutinib + CD20 Antibody and Venetoclax in Patients With Untreated Mantle Cell Lymphoma

Inclusion Criteria: 1. Patient is ≥ 18 years and \< 80 years of age at the time of signing the informed consent form (ICF). 2. Patient understood and voluntarily signed and dated an ICF prior to any study-specific assessments/procedures being conducted. 3. Patient willing and able to adhere to the study visit schedule and other protocol requirements 4. Women of childbearing potential must have negative results for pregnancy test prior to study treatment start and agree to abstain from breastfeeding during study participation and at least 18 months after the last drug administration 5. Men or women of reproductive potential agree to use acceptable method of birth control during treatment and for eighteen months after the last drug administration. 6. Histologically confirmed (according to the World Health Organization (WHO) classification) mantle cell lymphoma. The diagnosis has to be confirmed by phenotypic expression of CD5, CD20 and cyclin D1 or the t(11;14) translocation (by cytogenetics and/or fluorescence in situ hybridization (FISH) and/or BCL1-IgH PCR) 7. Untreated MCL 8. Adequate renal function as demonstrated by a creatinine clearance \> 50 mL/min; calculated by Cockcroft Gault formula or Modification of Diet in Renal Disease (MDRD) 9. Adequate hepatic function per local laboratory reference range as follow: * Aspartate transaminase (AST) and alanine transaminase (ALT) \< 3.0 x upper limit of normal (ULN) * Bilirubin \< 1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin) 10. Stage II-IV disease, measurable with at least lymph node \> 1.5 cm and requiring treatment in the opinion of the treating clinician 11. Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2. 12. Life expectancy of more than 3 months. 13. For France: patient affiliated to any social security system Exclusion Criteria: 1. Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification. 2. Impaired organ function (other than liver and renal) which will interfere with the treatment 3. Hemoglobin level \< 10g/dL; Neutrophil count \<1 G/L; Platelets \< 75 G/L (except if related to lymphoma then platelet must be \>50), 4. Major surgery within 28 days before enrollment 5. Known central nervous system lymphoma 6. History of stroke or intracranial hemorrhage within 6 months prior to enrollment. 7. Requires anticoagulation with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon) 8. Requires treatment with strong CYP3A inhibitors 9. Vaccinated with live, attenuated vaccines within 6 months of enrollment (except COVID vaccine) 10. Known history of human immunodeficiency virus (HIV) 11. Evidence of other clinically significant uncontrolled condition(s) including but not limited to: * Uncontrolled and/or active systemic infection (viral, bacterial or fungal) * Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. Note: subjects with serologic evidence of prior vaccination to HBV (i.e. HBs antigen negative, anti-HBs antibody + and antiHBc antibody -) and subjects with anti-HB-core antibody that are HBV DNA negative may participate 12. Psychiatric illness or condition which could interfere with their ability to understand the requirements of the study 13. Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator' opinion, could compromise the patient safety, interfere with the absorption or metabolism of treatment (Ibrutinib, CD20 Ab, venetoclax) or put the study outcomes at undue risk 14. Pregnant, planning to become pregnant, or lactating woman 15. Known hypersensitivity to study treatment (CD20 Ab, Ibrutinib, Venetoclax) or to any of the excipients 16. Known allergy to xanthine oxidase inhibitors or rasburicase 17. Known glucose-6-phosphate dehydrogenase (G6DP) deficiency 18. Known bleeding disorders 19. Severe prior reactions to monoclonal antibodies or with prior significant toxicity (other than thrombocytopenia) from Bcl-2 inhibitor 20. History of prior other malignancy with the exception of: * curatively treated basal cell carcinoma * curatively treated squamous cell carcinoma of the skin or carcinoma in situ of the cervix at any time prior to study * other curatively treated cancer and patient disease-free for over 5 years 21. Anti-cancer therapies including chemotherapy, radiotherapy or other investigational therapy, including targeted small molecule agents 22. Biological agents (e.g. monoclonal antibodies) for anti-neoplastic intent: excluded 30 days prior to first dose of venetoclax 23. Person deprived of his/her liberty by a judicial or administrative decision 24. Adult person under legal protection