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.
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.
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.
Single group
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Chimeric Antigen Receptor T-Cell Therapy
Biological/VaccineReceive CAR-T per standard of care
Computed Tomography
Procedure/SurgeryUndergo PET/CT
External Beam Radiation Therapy
RadiationUndergo radiation therapy
Leukapheresis
Procedure/SurgeryReceive leukapheresis
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Positron Emission Tomography
Procedure/SurgeryUndergo PET/CT
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.
Incidence of AEs
Will be assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0 except in the case of cytokine release syndrome and neurotoxicity, which will be graded by American Society for Transplantation and Cellular Therapy Consensus Grading and not NCI CTCAE v5.0. All participants who receive any fraction of protocol radiation are evaluable.
Objective response rate
Will be defined as the proportion of participants that achieve a best response of either complete response (CR) or partial response after CAR T-cell infusion and prior to disease progression and/or start of other anti-lymphoma therapy, along with its associated 95% Clopper Pearson exact binomial CI. Only participants who receive CAR T-cell infusion post protocol radiation are evaluable.
Complete response rate
Will be defined as the proportion of participants that achieve a best response of CR after CAR T-cell infusion and prior to disease progression and/or start of other anti-lymphoma therapy, along with its associated 95% Clopper Pearson exact binomial CI. Only participants who receive CAR T-cell infusion post protocol radiation are evaluable.
Progression free survival
Will be assessed only in participants who receive CAR T-cell infusion post protocol radiation are evaluable for this endpoint. Will be estimated for patients who received radiation and CAR T-cells using the Kaplan Meier method along with the Greenwood estimator of standard error; 95% confidence interval will be constructed based on log-log transformation.
Click on the lead sponsor to view all of their trials.
City of Hope Medical Center
Lead sponsor
National Cancer Institute (NCI)
Collaborator
