A Feasibility Trial of Tazemetostat Plus CAR T Cell Therapy in B-cell Lymphomas

This is a single arm, open label, clinical trial to evaluate the feasibility and safety of oral tazemetostat followed by standard of care CAR T cell infusion in previously treated DLBCL, FL, and MCL. The investigators hypothesis is that this combination has the potential to significantly improve the ability of CART cells to recognize and kill lymphoma cells without a significant impact on safety. Tazemetostat 800 mg will be given twice daily by mouth for at least 1 week prior to apheresis, during the period between apheresis and CAR T infusion, and following lymphodepletion chemotherapy until Day 7 post-CAR T therapy. Once patients' platelets and neutrophil counts recover, tazemetostat will be resumed. Tazemetostat treatment will continue for up to 6 months in patients with complete responses and up to 12 months in patients with partial responses. A 3+3 trial design will be implemented for the first six patients enrolled. The regimen will be considered feasible if at least 12 out of 15 subjects are able to receive at least 2 weeks of tazemetostat, generate the CAR T cell product and receive CAR T cell therapy.