Total Body Irradiation + Tisagenlecleucel for B-Cell Lymphoma

This phase I trial tests the safety, side effects, and best dose of total body irradiation (TBI) in combination with standard of care lymphodepletion with cyclophosphamide and fludarabine before tisagenlecleucel (Tisa-cel) and how well the combination works in patients with large B-cell lymphoma (LBCL) that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). TBI is a common treatment that sends radiation (for example, through x-rays) to the entire body. Lymphodepleting chemotherapy, such as cyclophosphamide and fludarabine, along with TBI helps kill cancer cells in the body and helps prepare the body for the Tisa-cel infusion. Tisagenlecleucel is made using a patient's T cells (a type of immune system cell). A gene for a special receptor called chimeric antigen receptor (CAR) is added to the T cells in the laboratory. These changed T cells called CAR T cells are grown in large numbers in the laboratory and given to the patient by infusion. Tisa-cel binds to a protein called CD19, which is found on some leukemia and lymphoma cells. This helps the body's immune system kill cancer cells. Tisa-cel is a type of CAR T-cell therapy. Giving low dose TBI in combination with standard of care lymphodepletion therapy and Tisa-cel may be safe, tolerable, and/or effective in treating patients with relapsed or refractory (R/R) LBCL.