Venetoclax in combination with Ibrutinib and Rituximab or conventionalchemotherapy (Bendamustine) and Ibrutinib and Rituximab in patientswith Mantle Cell Lymphoma.
- Conditions
- Mantle Cell LymphomaMedDRA version: 20.0Level: LLTClassification code: 10026799Term: Mantle cell lymphoma NOS Class: 10029104Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2022-501808-96-00
- Lead Sponsor
- niversitatsmedizin der Johannes Gutenberg-Universitat Mainz KöR
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 200
Histologically confirmed diagnosis of MCL according to WHO classification, Creatinine = 2 mg/dL or eGFR = 50 mL/min, Written informed consent form according to ICH/EU GCP and national regulations, Sexually active men with female partners of child-bearing potential potential must agree to use highly effective contraceptives, previously untreated stage II-IV (Ann Arbor), = 60 years and not suitable for autologous SCT, At least 1 measurable lesion; in case of bone marrow infiltration only, bone marrow aspiration and biopsy is mandatory for all staging evaluations., ECOG performance status = 2, Absolute neutrophil count (ANC) = 1000 cells/µL, Platelets =75.000 cells/µL, Transaminases (AST and ALT) =3 x ULN, Total bilirubin = 2 x ULN unless other reason known (Gilbert- Meulengracht-Syndrome)
Major surgery within 4 weeks prior to first dose, Pulmonary (e.g. chronic lung disease with hypoxemia, e.g. DLCO = 65% or FEV1 = 65%), Endocrinological (e.g. severe, not sufficiently controlled diabetes mellitus), Patients with unresolved hepatitis B or C infection or known HIV positive infection (mandatory test) Concomitant or previous malignancies within the last 3 years other than basal cell skin cancer, Prostate cancer in remission with PSA within normal range or in situ uterine cervix cancer, Requires anticoagulation with warfarin or equivalent vitamin K antagonists (e.g. phenprocoumon), History of stroke or intracranial hemorrhage within 6 months prior to first dose, Treatment with strong or moderate CYP3A4/5 inhibitors/inducers within 7 days before first dose and during Venetoclax and Ibrutinib intake, Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of Ibrutinib capsules, or put the study outcomes at undue risk, Vaccinated with live, attenuated vaccines within 4 weeks prior to first dose, Known CNS involvement of MCL, Known bleeding disorder (e.g. von Willebrand disease; hemophilia) Serious concomitant disease interfering with a regular therapy according to the study protocol, Cardiac (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 or LVEF below LLN)
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate efficacy in both treatment arms: Failure-Free Survival (FFS) at 30 months;Secondary Objective: Failure-free survival (continuous observation), Progression-free survival, Complete Remission rate (CR) and overall response rate (ORR: CR, PR) four weeks after the end of induction therapy, best response, time to best response, time to first response, overall survival, Overall survival of patients divided according to the geriatric categories and treatment received, Safety: adverse events, tolerability, Quality of life during induction and maintenance therapy (assessed using the EORTC QLQ-C30 and the EORTC QLQ-NHL-HG29), Molecular remission after induction and conversion during maintenance (exploratory), Immune reconstitution, e.g. persistence of anti-Covid19 immunity, safety and efficacy in different geriatric categories;Primary end point(s): To evaluate efficacy in both treatment arms: Failure-Free Survival (FFS) at 30 months
- Secondary Outcome Measures
Name Time Method Secondary end point(s):Failure-free survival (continuous observation);Secondary end point(s):Progression-free survival;Secondary end point(s):Complete Remission rate (CR) and overall response rate (ORR: CR, PR) four weeks after the end of induction therapy;Secondary end point(s):best response, time to best response, time to first response;Secondary end point(s):overall survival;Secondary end point(s):Overall survival of patients divided according to the geriatric categories and treatment received;Secondary end point(s):Safety: adverse events, tolerability;Secondary end point(s):Quality of life during induction and maintenance therapy (assessed using the EORTC QLQ-C30 and the EORTC QLQ-NHL-HG29);Secondary end point(s):Molecular remission after induction and conversion during maintenance (exploratory);Secondary end point(s):Immune reconstitution, e.g. persistence of anti-Covid19 immunity;Secondary end point(s):safety and efficacy in different geriatric categories