The purpose of this study is to test the safety and effectiveness of the experimental combination of tazemetostat with chimeric antigen receptor t-cell (CAR T) cell therapy, and see what effects it has on lymphoma. An additional purpose of this study is to understand what side effects people may have when they receive both drugs together.

Tazemetostat is a drug that inhibits EZH2, an enzyme known to drive the development of B-cell lymphomas, and inhibiting it appears to have many effects that slow down lymphoma growth and enhance the immune system’s ability to fight it. Tazemetostat is approved by the U.S. Food and Drug Administration (FDA) in previously treated follicular lymphoma, but is not currently FDA-approved for mantle cell lymphoma or diffuse large B-cell lymphoma. 

CAR T cell therapy is a therapeutic strategy that uses the immune system to fight lymphoma, called immunotherapy. T-cells are removed from patients, undergo manufacturing to give them the ability to seek out and destroy lymphoma cells, and then infused back into patients following chemotherapy called “lymphodepletion.” CAR T cell therapy is currently FDA-approved in previously treated diffuse large B-cell lymphoma, follicular lymphoma, and mantle cell lymphoma. 
   
Tazemetostat is not currently approved in combination with CAR T cell therapy and we do not know the effect that giving tazemetostat with CAR T cell therapy will have.

Participants will receive a regimen with tazemetostat both before and after CAR T cell therapy. CAR T cell therapy will be conducted in a similar fashion to those undergoing commercially available CAR T cell therapy, with cell collection in clinical followed by admission to the hospital for chemotherapy and cell infusion.

Tazemetostat is given in a form of tablets and will be taken by mouth approximately twice a day.

Participants will remain in the study for about 6 years.