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
3 other identifiers
interventional
9
1 country
1
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for early_phase_1
Started Jul 2023
Typical duration for early_phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 24, 2023
CompletedFirst Posted
Study publicly available on registry
April 5, 2023
CompletedStudy Start
First participant enrolled
July 20, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 4, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
January 4, 2027
February 4, 2026
February 1, 2026
3.5 years
March 24, 2023
February 2, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Proportion of participants completing planned radiation therapy
Will be assessed by the proportion of participants completing planned radiation therapy without any grade 3 or higher radiation-attributable (possibly, probably, or definitely) adverse events (AEs), along with its associated 95% Clopper Pearson exact binomial confidence interval (CI). All participants who start protocol radiation therapy are evaluable.
From the first fraction of radiation until approximately 1 month after infusion of chimeric antigen receptor (CAR) T-cell therapy
Secondary Outcomes (7)
Incidence of AEs
Up to 1 year
Objective response rate
Up to 1 year
Complete response rate
Up to 1 year
Progression free survival
Time from CAR T-cell infusion to time of disease relapse/progression or death due to any cause, whichever occurs first, assessed up to 1 year
Overall survival
Time from CAR T-cell infusion to time of death due to any cause, assessed up to 1 year
- +2 more secondary outcomes
Study Arms (1)
Treatment (leukapheresis, external beam radiation, CAR-T)
EXPERIMENTALPatients 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.
Interventions
Undergo blood sample collection
Receive CAR-T per standard of care
Undergo MRI
Undergo PET/CT
Undergo PET/CT
Undergo radiation therapy
Receive leukapheresis
Eligibility Criteria
You may qualify if:
- 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.
- 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.
You may not qualify if:
- 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).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- City of Hope Medical Centerlead
- National Cancer Institute (NCI)collaborator
Study Sites (1)
City of Hope Medical Center
Duarte, California, 91010, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Savita V Dandapani
City of Hope Medical Center
Study Design
- Study Type
- interventional
- Phase
- early phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 24, 2023
First Posted
April 5, 2023
Study Start
July 20, 2023
Primary Completion (Estimated)
January 4, 2027
Study Completion (Estimated)
January 4, 2027
Last Updated
February 4, 2026
Record last verified: 2026-02