A Study of Radiation Therapy Before CAR T Cell Therapy for People With B Cell Lymphoma

Inclusion Criteria:

Histologically confirmed, relapsed or refractory non-Hodgkin lymphoma patients eligible for a CAR T-cell therapy, such as DLBCL (including transformed follicular lymphoma), high grade B-cell lymphoma, primary mediastinal B-cell lymphoma, and follicular lymphoma of any grade
Patient is approved for, and planned to receive, anyone of the three commercially available anti-CD19 CAR T-cell products (axicabtagene ciloleucel, maraleucel or tisagenlecleucel)
Patient has at least one site of disease with avidity greater than liver on a screening FDG-PET scan performed within 2 months of RT simulation. Measurable disease is not required.
Active secondary central nervous system (CNS) lymphoma is allowed
Age 18 or older
ECOG status ≤2
Adequate bone marrow function without a requirement for blood product transfusion or growth factor support in the previous 7 days, unless the cytopenias are felt to be due to the underlying lymphoma in the best judgement of the study investigator:
Active secondary central nervous system (CNS) lymphoma is allowed
Age 18 or older
ECOG status ≤2

Adequate bone marrow function without a requirement for blood product transfusion or growth factor support in the previous 7 days, unless the cytopenias are felt to be due to the underlying lymphoma in the best judgement of the study investigator:

Absolute neutrophil count ≥ 1.0 k/µL
Platelets ≥ 50k /µL
Hemoglobin ≥ 7g/dL.
Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile or abstain from sexual activity for the course of the study through 120 days after the last dose of radiotherapy. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year. Note: Abstinence is acceptable if this is the established and preferred contraception for the subject
Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the established and preferred contraception for the subject

Exclusion Criteria:

Subject is planned to receive any systemic therapy after initiation of BRT and before re-infusion of CAR T cells including conventional chemotherapy, immunotherapy or targeted agents [Note: Planned lymphodepletion chemotherapy in preparation for CAR T cell administration is not an exclusion criterion]
Subject has received prior RT to any site(s) planned for bridging therapy such that the composite dose considering the protocol-mandated BRT would exceed normal tissue tolerances in the determination of the investigator.
The treating investigator deems that it would be impossible to comprehensively treat the patient with radiotherapy given concerns about feasibility or potential toxicities
Current or planned pregnancy
Known additional malignancy that is progressing or requires any treatment other than active surveillance or hormonal therapy. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study based on the investigator´s judgment