LV20.19 CAR T-Cells in Combination With Pirtobrutinib for Relapsed, Refractory B-cell Malignancies

To facilitate rapid start of pirtobrutinib, there will be separate inclusion/exclusion for pirtobrutinib and LV20.19 CAR T-cells in addition to the general inclusion as outlined below. General inclusion criteria for trial: 1. Patients must be aged ≥18 years and \<81 years with relapsed or refractory B-cell non-Hodgkin Lymphoma (NHL). 2. Diagnosis of relapsed or refractory B-cell NHL including Follicular Lymphoma, Marginal Zone Lymphoma (splenic, nodal, extranodal), Mantle Cell Lymphoma, Burkitt Lymphoma and DLBCL with associated subtypes (aggressive B-cell lymphoma, high grade B-cell lymphoma, T-cell/histocyte rich B-cell lymphoma, primary mediastinal B-cell lymphoma, Epstein-Barr virus-positive (EBV)+ diffuse large B-cell lymphoma, transformed lymphoma such as transformed follicular or marginal zone, and Richter's transformation). 3. Disease specific criteria as follows: 1. DLBCL and associated subtypes (listed above) i. Must have received Rituximab or another cluster of differentiation 20 (CD20) antibody with combination anthracycline based chemotherapy regimen and have ONE of the following: <!-- --> 1. Primary refractory lymphoma or early relapse ≤6 months after one line of therapy. 2. For relapse \>6.00 months, failure of two different chemotherapy regimens appropriate for their disease and be ineligible to receive autologous transplant. ii. Relapse post-autologous transplant. iii. Relapse post-allogeneic transplant. iv. Relapse post-CAR T-cell therapy (maximum 2 patients allowed with this designation). b. Mantle Cell Lymphoma i. Must have received Rituximab or another CD 20 antibody with one chemotherapy regimen appropriate for this disease (bendamustine or cytarabine, or anthracycline based treatment) and have ONE of the following: 1. Relapsed disease after two lines of cytotoxic chemotherapy including administration of anti-CD20 antibody. 2. Progressive disease after ≥second line BTK inhibitor. 3. Relapse post-autologous transplant. 4. Relapse post-allogeneic transplant. c. Marginal Zone Lymphoma and Follicular Lymphoma i. Must have received Rituximab or another CD20 antibody with chemotherapy regimen appropriate for the disease and have ONE of the following: <!-- --> 1. Relapsed disease after two lines of therapy including administration of anti-CD20 antibody. 2. Relapse post-autologous transplant. 3. Relapse post-allogeneic transplant. d. Burkitt's Lymphoma i. Must have received Rituximab or another CD20 antibody in combination with anthracycline based chemotherapy regimen and have ONE of the following: <!-- --> 1. Primary refractory lymphoma. 2. Relapse within 6 months. 3. For relapse \>6 months, failure of two different chemotherapy regimens appropriate for their disease and be ineligible to receive autologous transplant. i. Relapse post-autologous transplant. ii. Relapse post-allogeneic transplant. 4. Able to provide written informed consent. 5. Negative urine or serum pregnancy test in females of childbearing potential at screening. 6. Willingness of women of reproductive potential and their partners to observe highly effective birth control methods for duration of treatment and for 1 month following the last dose if study treatment. 7. Karnofsky performance score ≥70. 8. Expected survival \>12 weeks. 9. Patient has demonstrated compliance with prior therapies. 10. Able to take oral medications. 11. Adequate coagulation, defined as activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) and prothrombin (PT) or (international normalized ratio (INR) not greater than 1.5 x upper limit of normal (ULN). 12. Patients are required to have the following washout periods prior to planned Cycle 1 Day 1 (C1D1). In addition, prior treatment-related adverse events (AEs) must have recovered to Grade ≤ 1 with the exception of alopecia and Grade 2 peripheral neuropathy. 1. Targeted agents, investigational agents, therapeutic monoclonal antibodies or cytotoxic chemotherapy: 5 half-lives or 2 weeks, whichever is shorter. 2. immunoconjugated antibody treatment within 10 weeks prior to randomization. 3. broad field radiation (≥ 30% of the bone marrow or whole brain radiotherapy) must be completed 14 days prior to study enrollment. 4. palliative limited field radiation must be completed 7 days prior to study enrollment. Inclusion Criteria to START Pirtobrutinib Bridging: 1. Absolute neutrophil count (ANC) ≥1000 with no G-CSF within 7 days or pegylated G-CSF within 14 days unless patient has biopsy proven bone marrow involvement. 2. Platelets≥50,000 with no transfusion within 7 days unless patient has biopsy proven bone marrow involvement. 3. Hemoglobin ≥8g/dL (≥80 g/L) \[blood transfusions are allowable to reach this goal\]. 4. Adequate hepatic function, defined as aspartate aminotransferase (AST) and alanine transaminase (ALT) \<3 x upper limit of normal (ULN) or \< 5 x ULN with documented liver involvement; serum bilirubin \<1.5 x ULN or \<3 x ULN with documented liver involvement , or considered not clinically significant as per the clinical PIs discretion (e.g. Gilbert's or indirect hyperbilirubinemia) or felt to be due to underlying disease. 5. Adequate renal function, defined as creatinine clearance≥50 ml/min. 1. No IV hydration within 24 hours of eligibility. 2. No dialysis dependent renal failure. Inclusion criteria for Pirtobrutinib Maintenance (part B) 1. Recovery of neutrophils count after CAR T-cell infusion with ANC ≥1000/dL without G-CSF within the last 7 days. 2. Recovery of platelet count after CAR T-cell infusion with platelet count ≥50,000/dL. 3. Adequate hepatic function, defined as back to baseline or AST and ALT \<3 x upper limit of normal (ULN); serum bilirubin and alkaline phosphatase \<3 x ULN, or considered not clinically significant as per the clinical PI's discretion (e.g., Gilbert's or indirect hyperbilirubinemia) or felt to be due to underlying disease. 4. Adequate renal func