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

Official title

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

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.

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.

Interventions

• 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

Primary outcome measures

• Proportion of participants completing planned radiation therapy [Time frame: From the first fraction of radiation until approximately 1 month after infusion of chimeric antigen receptor (CAR) T-cell therapy]

Secondary outcome measures (7)

• Incidence of AEs [Time frame: Up to 1 year]
• Objective response rate [Time frame: Up to 1 year]
• Complete response rate [Time frame: Up to 1 year]
• Progression free survival [Time frame: 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 frame: Time from CAR T-cell infusion to time of death due to any cause, assessed up to 1 year]
• Local control [Time frame: Time from CAR T-cell infusion to time of disease relapse/progression within the radiation field, assessed up to 1 year]
• Distant control [Time frame: Time from CAR T-cell infusion to time of disease relapse/progression outside the radiation field, assessed up to 1 year]

Eligibility criteria

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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• City of Hope Medical Center — Duarte

Identifiers

NCT: NCT05800405 · 22141 · NCI-2023-02190 · 22141 · P30CA033572

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗