Frontline Risk-Adapted Optimization of Novel Targeted Immunotherapy Evaluation in High-Risk MCL

Inclusion Criteria: * Diagnosis of MCL requires histologic confirmation by either overexpression of cyclin D1 OR presence of t(11;14) (q13; q32) translocation 1. Subject should have a tumor biopsy sample (at least 5 unstained slides of tissue or tissue block) available prior to MB-CART2019.1 infusion, preferably collected pre-induction. 2. If archival tissue is not available, the patient may be enrolled after discussion with the protocol chair and/or protocol officer * High Risk Disease at diagnosis, defined as having at least ONE of the criteria below: 1. High risk MIPI-c (as calculated by https://www.european-mcl.net/home/scores-mipi-mipi-c-19.html) 2. Simplified MIPI high-risk ≥6.2 3. TP53 mutation OR ≥50% TP53 expression by IHC 4. Complex Karyotype \[e.g. 3 or more cytogenetic abnormalities, excluding the presence or absence of t(11:14)\] 5. Ki67≥ 50% 6. Blastoid or pleomorphic histology with Ki-67 ≥30% 7. Leptomeningeal Disease at diagnosis 8. NOTCH1 mutation * Received 2 cycles of appropriate systemic induction therapy, which includes a CD20 antibody +/- cytotoxic therapy +/- oral targeted therapy (e.g., BTKi, immunomodulatory imid drugs), with the following considerations: 1. CD20 antibody alone does not count towards a cycle of treatment 2. Induction cycles do not have to be identical 3. For BTKis and/or lenalidomide a cycle is defined as 14-28 days and will be based on institutional treatment regimens. 4. Intrathecal chemotherapy will not count towards a cycle of treatment 5. Radiation therapy will not count towards a cycle of treatment * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening. ECOG performance status of 2 at screening is allowed if the decrease in performance status is attributed to lymphoma * Disease response assessment of either complete response, partial response, or stable disease by Lugano 2014 criteria assessed by 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) (preferred) or contrast enhanced CT scans including neck/chest/abdomen/pelvis \[37\] after 2 cycles of induction therapy. If the participant has history of CNS disease, then he/she must have no history of or active parenchymal disease on magnetic resonance imaging (MRI) a. Leptomeningeal alone disease is allowable if it is not clinically progressive or worsening from baseline assessment * A creatinine clearance (as estimated by direct urine collection, Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\], or Cockcroft-Gault Equation or institutional standard) ≥ 45 mL/min * Subjects of childbearing or child fathering potential must be willing to practice birth control from the time of enrollment on this study until the follow-up period of the study Exclusion Criteria: * Unable to give informed consent * Any disease progression that occurs during the first 2 induction cycles * A creatinine clearance (as estimated by direct urine collection, Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\], or Cockcroft-Gault Equation or institutional standard) \< 45 mL/min * Cardiac ejection fraction (EF) \< 45% as determined by an echocardiogram (ECHO) or Multigated Radionuclide Acquisition scan (MUGA) (if range is provided, the upper value of the range may be used for assessing eligibility) * Resting O2 saturation \< 92% on room air * Serum alanine aminotransferase (ALT) / aspartate aminotransferase (AST) ≥ 5 times the Upper Limit of Normal (ULN) for age * Total bilirubin \>1.5 mg/dL, except in individuals with Gilbert's syndrome * Absolute neutrophil count (ANC) \< 1000/μL unless related to bone marrow infiltration by mantle cell lymphoma. No short-acting granulocyte colony-stimulating factor (G-CSF) use within 7 days of ANC evaluation * Platelet count \< 50,000/µL unless related to bone marrow infiltration or hypersplenism by mantle cell lymphoma. No transfusions within 7 days of assessment. * Absolute CD3 count \< 50/μL at screening * Absolute lymphocyte count (ALC) \< 100/μL within 7 days of apheresis * Known history of infection with human immunodeficiency virus (HIV) * Known active infection with hepatitis B (hepatitis B surface antigen \[HBsAg\] positive). If there is a history of treated hepatitis B, the viral load must be polymerase chain reaction (PCR) negative; antiviral prophylaxis is required if HBsAg negative and anti-hepatitis B core (HBc) positive * Known active infection with hepatitis C virus (anti-HCV antibody positive). If patient has a positive hepatitis C antibody, the viral load must be undetectable per quantitative PCR and/or nucleic acid testing * No seizure history within 6 months prior to enrollment * Known history of cerebral vascular accident (CVA) within prior 12 months * Known history or presence of autoimmune CNS disease, such as multiple sclerosis, optic neuritis or other immunologic /or inflammatory diseases * Presence of active CNS disorder that, in the judgment of the investigator, may impair the ability to evaluate neurotoxicity * Uncontrolled bacterial, viral, or fungal infection at the time of enrollment. a. Uncontrolled is defined as currently taking medication and with progression or no clinical improvement on adequate medical treatment * Pregnant or breast-feeding woman * Previous or concurrent malignancy with the following exceptions: 1. Adequately treated basal cell or squamous cell carcinoma (adequate wound healing is required prior to study entry) 2. In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 2 years prior to the study 3. Adequately treated breast or prostate carcinoma on hormonal therapies such as Lupron or tamoxifen and in clinical remission of ≥ 2 years -or- low-grade untreated prostate cancer under observation 4. A primary malignancy which has been completely resected / treated with curative intent and in complete remission of ≥ 2 years 5. Subjects with prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with safety and efficacy assessment are eligible for this trial after discussion with protocol chair or protocol officer * Severely immunocompromised participants e.g. due to current systemic treatment of non-neurologic autoimmune disease (e.g. Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus) * Medical condition requiring prolonged use of systemic corticosteroids equivalent to prednisone \>10 mg/day. * History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 6 months of enrollment * For systemic therapy or radiation therapy, at least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed at the time of scheduled leukapheresis * BTKis can be continued through apheresis until one day prior to start of lymphodepletion * Baseline neurologic deficits that would interfere with therapy or monitoring, determined using Immune Effector Cell-Associated Encephalopathy (ICE) Assessment at baseline * History of severe immediate hypersensitivity reaction to any of the agents in this study * Refusal or inability to participate in additional lentiviral gene therapy long-term follow-up (LTFU) protocol * Prior CAR-T therapy for any indication or systemic gene-modifying therapy for B cell lymphoma * Prior allogeneic stem cell transplant for any indication. * Prior bispecific T cell engaging (BITE) antibodies for cancer therapy * Prior T cell receptor-engineered T cell therapy