evaluation of bridging radiation therapy before car t-cell infusion for the treatment of relapsed or refractory large b-cell lymphoma

Conditions: Recurrent Diffuse Large B-Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma

Summary: this early phase i clinical trial evaluates bridging radiation therapy given before chimeric antigen receptor (car) t-cell infusion to treat large b-cell lymphoma (lbcl) that has come back (relapsed) or has not responded to previous treatment (refractory). patients with relapsed or refractory disease have historically poor prognosis. car t-cell therapy is a type of treatment in which a patient's t-cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. t-cells are taken from a patient's blood (leukapheresis). then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the t-cells in the laboratory. the special receptor is called a chimeric antigen receptor (car). large numbers of the car t-cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. while the outcomes from car t-cell therapy appear favorable, in the time between leukapheresis and car t-cell infusion many patients have symptomatic or life-threatening disease which often requires bridging therapy. bridging therapy aims to slow disease progression and control symptoms during this critical period prior to car t-cell infusion. radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells. giving bridging radiation therapy to patients with relapsed or refractory lbcl prior to car t-cell infusion may improve treatment outcomes with minimal toxicity.

primary objective: i. evaluate if bridging radiation to all sites of f-fluorodeoxyglucose (fdg)-avid disease can be feasibly administered prior to commercial car t-cell infusion in patients with large b-cell lymphoma (lbcl). secondary objectives: i. assess the toxicities of bridging radiation in patients with lbcl. ii. assess overall response rate, complete response rate, progression-free survival, local control, distant control, and overall survival after bridging radiation and car t-cell infusion in patients with lbcl. exploratory objectives: i. bank blood for future immune profiling or other correlatives. ii. explore the association between positron emission tomography (pet)/computed tomography (ct) radiomic features and clinical outcomes. iii. collect pet/ct imaging data using the reflexion x1 linear accelerator imaging system. outline: patients undergo leukapheresis per standard of care, undergo external beam radiation therapy, and undergo car t-cell infusion per standard of care on study. patients undergo pet/ct throughout the study and may undergo magnetic resonance imaging (mri) during screening. patients also undergo blood sample collection throughout the study.

Eligibility criteria:
inclusion criteria: * documented informed consent of the participant and/or legally authorized representative. * assent, when appropriate, will be obtained per institutional guidelines. * age: \>= 18 years. * eastern cooperative oncology group (ecog) =\ = 60. * histologically confirmed large b-cell lymphoma. * relapsed/refractory disease. * planned to undergo commercial car t-cell infusion within 3 months of enrollment. * 6 or fewer sites (treatable with a maximum of 3 isocenters) of fdg-pet avid disease, treatable with a a maximum of 3 isocenters. * measurable disease e.g., at least 1.5 cm on ct/mri or by response evaluation criteria in solid tumors 1.1 (recist 1.1). * fully recovered from the acute toxic effects (except alopecia) to =\< grade 1 to prior anti-cancer therapy. * women of childbearing potential (wocbp): negative urine or serum pregnancy test (performed within 30 days prior to day 1 of protocol therapy). * if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. exclusion criteria: * prior cd19-directed therapy. * radiation therapy within 21 days prior to day 1 of protocol therapy. * central nervous system (cns) disease. * history of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent. * active diarrhea. * clinically significant uncontrolled illness. * active infection requiring antibiotics. * other active malignancy. * females only: pregnant. * any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures. * prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics).