NCT05800405

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

A Feasibility Study of Bridging Radiation to All Sites of FDG-Avid Disease for Commercial CAR T-Cell Infusion in Patients With Large B-Cell Lymphoma

• Status: Recruiting
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 9 (estimated)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed 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.

Conditions

• Recurrent Diffuse Large B-Cell Lymphoma
• Refractory Diffuse Large B-Cell Lymphoma

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
BIOLOGICAL	Chimeric Antigen Receptor T-Cell Therapy	Receive CAR-T per standard of care
PROCEDURE	Computed Tomography	Undergo PET/CT
RADIATION	External Beam Radiation Therapy	Undergo radiation therapy
PROCEDURE	Leukapheresis	Receive leukapheresis
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
PROCEDURE	Positron Emission Tomography	Undergo PET/CT

Timeline

• Start date: 2023-07-20
• Primary completion: 2027-01-04
• Completion: 2027-01-04
• First posted: 2023-04-05
• Last updated: 2026-02-04

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study