PRIMARY OBJECTIVE:~I. To determine efficacy of adjunctive zanubrutinib with chimeric antigen receptor T (CAR T)-cell therapy as defined by an improvement in 6-month complete response rates (CR) (defined per 2014 Lugano criteria) as compared to historical rates, in patients treated with CAR T-cell therapy (with a prior lead-in zanubrutinib) followed by maintenance zanubrutinib.~SECONDARY OBJECTIVES:~I. To determine the conversion rates of partial (PR) to complete response (CR), defined per Lugano criteria (2014), in patients with partial response to initial CAR T-cell therapy (with a prior lead-in zanubrutinib) who are administered maintenance zanubrutinib.~II. To determine the overall response rate (ORR), using Lugano criteria (2014), in patients treated with CAR T-cell therapy (with a prior lead-in zanubrutinib) who are administered maintenance zanubrutinib.~III. To determine progression free survival (PFS), in patients treated with CAR T-cell therapy (with a prior lead-in zanubrutinib) who are administered maintenance zanubrutinib.~IV. To determine the overall survival (OS) rate in patients treated with CAR T-cell therapy (with a prior lead-in zanubrutinib) who are administered maintenance zanubrutinib.~V. Toxicity assessment.~EXPLORATORY OBJECTIVES:~I. To determine the impact on quality of life using the health-related quality of life outcome questionnaire European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ C-30), in patients treated with CAR T-cell therapy (with a prior lead-in zanubrutinib) who are administered maintenance zanubrutinib.~II. To measure disease-specific symptoms and/or treatment-related concerns in patients treated with CAR T-cell therapy (with a prior lead-in zanubrutinib) who are administered maintenance zanubrutinib.~III. To evaluate CAR T-cell polyfunctionality with the administration of zanubrutinib lead-in and maintenance treatment.~IV. To identify changes in immune cell subsets and cytokines with administration of zanubrutinib lead-in and maintenance.~V. To characterize potential mechanisms of loss of response by measuring changes in programmed cell death ligand-1 /2 (PD-L1/L2) and CD19 on tumor tissue.~OUTLINE:~LEAD- IN PHASE: Patients receive zanubrutinib orally (PO) twice daily (BID) for 7-14 days in the absence of disease progression or unacceptable toxicity.~CAR T-CELL THERAPY: Patients receive standard of care CAR T-cell therapy intravenously (IV) at 4 weeks.~MAINTENANCE PHASE: Patients receive zanubrutinib PO BID on days 1-28. Cycles repeat every 28 days for 12 months in the absence of disease progression or unacceptable toxicity.
This phase II trial studies the effect of zanubrutinib and CAR T-cell therapy in treating patients with aggressive B-cell non-Hodgkin's lymphoma or transformed indolent B-cell lymphoma that has come back (recurrent) or does not respond to treatment (refractory). Zanubrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. T cells are infection fighting blood cells that can kill tumor cells. The T cells given in this study will come from the patient and will have a new gene put in them that makes them able to recognize CAR, a protein on the surface of cancer cells. These CAR-specific T cells may help the body's immune system identify and kill cancer cells. Giving zanubrutinib together with CAR T-cell therapy may kill more cancer cells.