This phase Ib trial tests the safety, side effects, and best dose of autologous anti-prostate stem cell antigen (PSCA)-chimeric antigen receptor (CAR)-4-1BB/TCRzeta-CD19t-expressing T-lymphocytes (PSCA-CAR T cells), plus or minus radiation, in treating patients with castration-resistant prostate cancer that has spread from where it first started (primary site) to other places in the body (metastatic). Castration-resistant prostate cancer continues to grow and spread despite the surgical removal of the testes or medical intervention to block androgen production. 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. 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. Radiation therapy uses high energy x-rays to kill cancer cells and shrink tumors. Giving PSCA-targeting CAR T-cells, with or without radiation, may kill more tumor cells in men with castration-resistant prostate cancer.
Documented informed consent of the participant and/or legally authorized representative (brown)
Assent, when appropriate, will be obtained per institutional guidelines
Note: For research participants who do not speak English, a short form consent may be used with a City of Hope (COH) certified interpreter/translator to proceed with screening and leukapheresis, while the request for a translated main consent is processed. However, the research participant is allowed to proceed with lymphodepletion and CAR T cell infusion only after the translated main consent form is signed
Agreement to allow the use of archival tissue from diagnostic tumor biopsies
Concurrent use of systemic steroids or chronic use of immunosuppressant medications. Recent or current use of inhaled steroids is not exclusionary. Physiologic replacement of steroids (prednisone =< 7.5 mg /day, or hydrocortisone =< 20 mg /day) is allowed
Subjects with clinically significant arrhythmia or arrhythmias not stable on medical management within two weeks of screening
Subjects with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system, including seizure disorder
History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
Single group
Autologous Anti-PSCA-CAR-4-1BB/TCRzeta-CD19t-expressing T-lymphocytes
Biological/VaccineGiven IV
Biopsy
Procedure/SurgeryUndergo tumor biopsy
Biospecimen Collection
Procedure/SurgeryUndergo blood, stool, and urine sample collection
Bone Scan
Procedure/SurgeryUndergo bone scan
Computed Tomography
Procedure/SurgeryUndergo CT scan
External Beam Radiation Therapy
RadiationUndergo radiation
Leukapheresis
Procedure/SurgeryUndergo leukapheresis
Lymphodepletion Therapy
Procedure/SurgeryUndergo lymphodepletion
Incidence of adverse events
Dose limiting toxicities (DLTs), cystitis, grade 3 toxicities and the full toxicity profile as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5 and cytokine release syndrome (CRS) and neurotoxicity as assessed by modified CRS grading. The recommended phase 2 dose (RP2D) will be based on the treatment plan 2 toxicity, activity and correlative data. Rates and associated 90% Clopper and Pearson binomial confidence limits will be estimated for DLTs within the DLT period. Tables will be created to summarize all toxicities and side effects by attribution to treatment arm, dose, organ and severity.
50% prostate specific antigen (PSA) level reduction
Statistical and graphical methods will be used to describe cytokine levels (peripheral blood) and PSA levels over the study period.
Persistence of CAR T cells
Maximum persistence (in days) will be described by treatment plan, recognizing the number of CAR T cycles the participant received.
Expansion of CAR T cells
Peak expansion (log10 copies/ug of genomic deoxyribonucleic acid \[DNA\]) will be described by treatment plan, recognizing the number of CAR T cycles the participant received.
PSCA tumor expression
PSCA expression on tumor cells by IHC and/or flow cytometry.
Serum cytokine profile
Statistical and graphical methods will be used.
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City of Hope Medical Center
Lead sponsor
National Cancer Institute (NCI)
Collaborator
