Early Treatment Intensification in Patients With High Risk Mantle Cell Lymphoma Using CAR-T-cell Treatment After an Abbreviated Induction Therapy With Rituximab and Ibrutinib and 6 Months Ibrutinib Maintenance (Arm A) as Compared to Standard of Care Induction and Maintenance (Arm B)
First-line CAR-T-cell consolidation after an abbreviated induction with 2 cycles of Rituximab and Ibrutinib prior to CAR-T-cell treatment and followed by 6 months of maintenance with Ibrutinib in patients with high risk MCL.
• Histologically confirmed diagnosis of MCL according to WHO classification, with documentation of either overexpression of cyclin D1 or presence of t(11;14)
• At least one High Risk MCL - feature as defined as I. MIPI-c high intermediate (HI) or high (H) risk (i.e. high risk MIPI irrespective of Ki-67 or intermediate risk MIPI and Ki-67\>=30% (Ki-67 based on local pathology) and/or II. TP53-mutation and/or TP53-overexpression by immunohistochemistry (\> 50% of lymphoma cells)
• No prior treatment for MCL
• Stage II-IV (Ann Arbor)
• 18-75 years
• At least 1 measurable lesion according to the Lugano Response Criteria (\>1.5 cm nodal lesion or \> 1cm extranodal lesion); in case of bone marrow infiltration only, bone marrow aspiration and biopsy is mandatory for all staging evaluations.
• ECOG performance status ≤ 2
• The following laboratory values at screening (unless discrepancies are related to MCL):
• I. Absolute neutrophil count (ANC) ≥ 1000 cells/μL II. Platelets ≥75,000 cells/μL III. Creatinine \<2 mg/dL or calculated creatinine clearance ≥60 mL/min IV. Transaminases (AST and ALT) \< 2.5 x ULN V. Total bilirubin \<= 2 x ULN unless other reason known (e.g. Gilbert-Meulengracht-Syndrome, or due to lymphoma involvement)
• No evidence of CNS-disease
⁃ Written informed consent form according to ICH/EU GCP and national regulations, ability to follow study instructions and likely to attend and complete all required visits
⁃ Sexually active men and women of child-bearing potential must agree to use one of the highly effective contraceptive methods (combined oral contraceptives using two hormones, contraceptive implants, injectables, intrauterine devices, sterilized partner) together with one of the barrier methods (latex condoms, diaphragms, contraceptive caps) while on study; this should be maintained for 6 months after the last dose of KTE-X19 or for 3 months after last dose of Ibrutinib, whichever is longer
⁃ Negative serum or urine pregnancy test (Females of childbearing potential only, Females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential)
⁃ Willingness not to drive a motor vehicle for 8 weeks post CAR T cell treatment
⁃ Possibility to reach the site within 2 hours in case of toxicity / emergency