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

Description

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.

Conditions

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

Study Overview

Study Details

Study overview

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.

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

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

Condition
Recurrent Diffuse Large B-Cell Lymphoma
Intervention / Treatment

-

Contacts and Locations

Duarte

City of Hope Medical Center, Duarte, California, United States, 91010

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility 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.
  • * 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).

Ages Eligible for Study

18 Years to

Sexes Eligible for Study

ALL

Accepts Healthy Volunteers

No

Collaborators and Investigators

City of Hope Medical Center,

Savita V Dandapani, PRINCIPAL_INVESTIGATOR, City of Hope Medical Center

Study Record Dates

2025-10-20