Evaluation of Bridging Radiation Therapy Before CAR T-Cell Infusion for the Treatment of Relapsed or Refractory Large B-Cell Lymphoma

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) =\< 2 or Karnofsky Performance Status (KPS) \>= 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).