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

City of Hope

Status and phase: Enrolling; Early Phase 1

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

Treatments: Radiation: External Beam Radiation Therapy; Biological: Chimeric Antigen Receptor T-Cell Therapy; Procedure: Computed Tomography; Procedure: Leukapheresis; Procedure: Positron Emission Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Biospecimen Collection

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT05800405

22141 (Other Identifier)

P30CA033572 (U.S. NIH Grant/Contract)

NCI-2023-02190 (Registry Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 9 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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9 participants in 1 patient group

Treatment (leukapheresis, external beam radiation, CAR-T)

Experimental group

Description:

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 MRI during screening. Patients also undergo blood sample collection throughout the study.

Treatment:

Procedure: Biospecimen Collection

Procedure: Magnetic Resonance Imaging

Procedure: Positron Emission Tomography

Procedure: Leukapheresis

Procedure: Computed Tomography

Biological: Chimeric Antigen Receptor T-Cell Therapy

Radiation: External Beam Radiation Therapy