PRIMARY OBJECTIVE:~I. To assess the increase in CD27+/CD28+ T cells, after 2-week exposure duvelisib prior to collection of mononuclear cells for chimeric antigen receptor T-cell (CART cell) manufacturing.~SECONDARY OBJECTIVES:~I. To evaluate patient compliance with duvelisib. II. To evaluate the time required for manufacturing CAR-T using mononuclear cells from duvelisib-treated patients.~III. To describe the frequencies of CD27/28 double positive T cells and CD4/8 double negative T cells.~IV. To estimate overall response rates following CART therapy. V. To describe the rates of intensive care unit (ICU) transfer due to cytokine release syndrome (CRS) and/or neurotoxicity or CRS or neurotoxicity that requires treatment with tocilizumab and/or corticosteroids after CAR-T cell therapy.~VI. To describe the safety and tolerability profile of duvelisib throughout the entire study (during duvelisib priming for 2 weeks and after CAR-T infusion for 3 months).~OUTLINE:~Patients receive duvelisib orally (PO) twice daily (BID) for 2 weeks prior to collection of CAR-T cells in the absence of disease progression or unacceptable toxicity. Patients then receive tisagenlecleucel via infusion.~Patients are followed up 100 days after CAR-T infusion.
This early phase I trial investigates how well duvelisib exposure before CAR-T cell manufacturing works to enhance immune profiles of T cells in patients with diffuse large B-cell lymphoma that has come back (recurrent) or does not respond to treatment (refractory). Duvelisib, an oral phosphoinositide 3-kinase (PI3K) inhibitor, may favorably change a patient's T cells to make them more efficient and have a longer duration for manufacturing of CAR-T cells.