Lisocabtagene Maraleucel, Nivolumab and Ibrutinib for the Treatment of Richter's Transformation

This phase II trial tests how well adding lisocabtagene maraleucel (liso-cel) to nivolumab and ibrutinib works in treating patients with Richter's transformation. Liso-cel is in a class of medications called autologous cellular immunotherapy, a type of medication prepared by using cells from patient's own blood. It works by causing the body's immune system (a group of cells, tissues, and organs that protects the body from attack by bacteria, viruses, cancer cells and other substances that cause disease) to fight the cancer cells. Nivolumab is in a class of medications called monoclonal antibodies. It works by helping the immune system to slow or stop the grown of cancer. Ibrutinib is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal protein that signals cancer cells to multiply. This helps stop the spread of cancer cells. Giving ibrutinib and nivolumab with Liso-cel may kill more cancer cells in patients with Richter's transformation.

Inclusion Criteria:Documented informed consent of the participantAgreement for confirmatory pre-treatment tumor biopsyIf a patient does not have an easily accessible lymph node to biopsy without excessive risk in the opinion of the investigator, archival biopsy material reviewed by a hematopathologist at the enrolling site for study eligibility and baseline correlatives may be acceptable with approval from the Study principal investigator (PI)Age: >= 18 yearsEastern cooperative oncology group (ECOG) <= 2Histologically confirmed Richter's Transformation (RT)Relapsed / refractory following >=2 prior lines of systemic therapy; OR refractory to first-line chemoimmunotherapy; OR relapsed within 12 months of first line chemoimmunotherapy; OR relapsed after first line of chemoimmunotherapy and not eligible for hematopoietic stem cell transplantation due to comorbidities or ageEligible to receive liso-cel and ibrutinib per package insertsFully recovered from the acute toxic effects (except alopecia) to <= Grade 1 to prior anti-cancer therapyAbsolute neutrophil count (ANC) >= 750/mm^3 unless there is bone marrow involvementPlatelets >= 75,000/mm^3 unless there is bone marrow involvementTotal bilirubin =< 1.5 X ULN (unless has Gilbert's disease)Aspartate aminotransferase (AST) =< 2.5 x ULNAlanine aminotransferase (ALT) =< 2.5 x ULNCreatinine clearance of >= 30 mL/min per 24 hour urine test or the Cockcroft-Gault formulaInternational Normalized Ratio (INR) OR Prothrombin (PT) =< 1.5 x ULNActivated Partial Thromboplastin Time (aPTT) =< 1.5 x ULNLeft ventricular ejection fraction (LVEF) >= 40%Note: To be performed within 28 days prior to Day 1 of protocol therapy.Seronegative for HCV*, active HBV (Surface Antigen Negative), and syphilis (RPR)If positive, Hepatitis C RNA quantitation must be performed ORIf seropositive for HCV or HBV, nucleic acid quantitation must be performed. Viral load must be undetectableMeets other institutional and federal requirements for infectious disease titer requirementsNote: Infectious disease testing to be performed within 28 days prior to Day 1 of protocol therapyWomen of childbearing potential (WOCBP): negative urine or serum pregnancy testIf the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be requiredAgreement by females and males of childbearing potential* to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 5 months after the last dose of protocol therapyChildbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)Exclusion Criteria:Subjects who previously received PD1 or PD-L1 inhibitor therapyAutologous stem cell transplant within 3 months prior to Day 1 of protocol therapyAllogeneic stem cell transplant within 3 months prior to Day 1 of protocol therapy and no active graft versus host disease (GVHD) or need for immunosuppressantsChemotherapy, radiation therapy, immunotherapy within 14 days prior to Day 1 of protocol therapyStrong CYP3A inducers within 14 days prior to Day 1 of protocol therapyWarfarin within 5 days prior to Day 1 of protocol therapyCurrent requirement for oxygen supplementationConcurrent use of systemic steroids or chronic use of immunosuppressant medications. Recent or current use of inhaled steroids is not exclusionary. Physiologic replacement of steroids (prednisone =< 7.5 mg /day or equivalent) is allowed throughout the study. Use of "bridging" steroids, to control disease, after leukapheresis and until 3 days prior to CAR T cell infusion, is allowedSubjects with lymphoma only involving the central nervous systemClass III/IV cardiovascular disability according to the New York Heart Association (NYHA) ClassificationSubjects with clinically significant arrhythmia or arrhythmias not stable on medical management within two weeks of screeningSubjects with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system, including seizure disorderSubjects with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to study agentKnown bleeding disorders (e.g., von Willebrand's disease) or hemophiliaHistory of stroke or intracranial hemorrhage within 6 months prior to screeningHistory of other malignancies, except for malignancy surgically resected (or treated with other modalities) with curative intent, basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; non-muscle invasive bladder cancer; malignancy treated with curative intent with no known active disease present for >= 3 yearsClinically significant uncontrolled illnessActive infection requiring antibioticsKnown history of immunodeficiency virus (HIV)Females only: Pregnant or breastfeedingSubjects with an active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis) not requiring systemic treatment, well controlled asthma and/or mild allergic rhinitis (seasonal allergies) are eligibleAny other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study proceduresProspective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)