Study to compare the efficacy and safety of the combinaison of venetoclax+ibrutinib in patients with untreated mantle cell lymphoma

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 194

Inclusion Criteria

Histologically confirmed (according to the 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 FISH and/or BCL1-IgH PCR)

OR

Untreated MCL

OR

Stage II-IV disease, measurable with at least lymph node > 1.5 cm and requiring treatment in the opinion of the treating clinician
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 154
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

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., phenprocoumone)
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 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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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