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Combining Ibrutinib, CD20 Antibody, and Venetoclax for Untreated Mantle Cell Lymphoma

A Randomized Phase II Trial Evaluating Ibrutinib Plus CD20 Ab and Venetoclax in Patients With Untreated Mantle Cell Lymphoma

Phase 2 Interventional The Lymphoma Academic Research Organisation · NCT04802590

This study is testing a new combination of treatments for people newly diagnosed with Mantle Cell Lymphoma to see which option works best in reducing the cancer after six months.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment194 (estimated)
Ages18 Years to 79 Years
SexAll
SponsorThe Lymphoma Academic Research Organisation Academic / other
Drugs / interventionsIbrutinib, chemotherapy
Locations45 sites (Bruges and 44 other locations)
Trial IDNCT04802590 on ClinicalTrials.gov

What this trial studies

This trial evaluates the effectiveness of a combination treatment involving Ibrutinib and a CD20 antibody, with or without Venetoclax, in patients newly diagnosed with Mantle Cell Lymphoma. It is a multicenter, open-label, randomized phase II trial that aims to determine the minimal residual disease (MRD) status at six months after treatment initiation. Patients aged 18 to 80 will receive treatment for a maximum of two years with Ibrutinib and Venetoclax, while the CD20 antibody will be administered for 3.5 years. The study seeks to compare the outcomes of the two treatment arms to identify the most effective regimen.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 80 with histologically confirmed Mantle Cell Lymphoma.

Not a fit: Patients with other types of lymphoma or those who are not newly diagnosed may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment combination could significantly improve outcomes for patients with untreated Mantle Cell Lymphoma.

How similar studies have performed: Other studies have shown promise with similar combination therapies in treating various types of lymphoma, indicating potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
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

Where this trial is running

Bruges and 44 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Mantle Cell Lymphoma
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.