PSCA-CAR T Cells in Treating Patients With PSCA+ Metastatic Castration Resistant Prostate Cancer
Condition: Castration-Resistant Prostate Carcinoma; Metastatic Prostate Carcinoma; Stage IV Prostate Cancer AJCC v8; Stage IVA Prostate Cancer AJCC v8; Stage IVB Prostate Cancer AJCC v8
MeSH terms: Carcinoma; Prostatic Neoplasms
Intervention: Autologous Anti-PSCA-CAR-4-1BB/TCRzeta-CD19t-expressing T-lymphocytes; Cyclophosphamide; Fludarabine; Fludarabine Phosphate
Intervention description: Given IV; Given IV; Given IV; Given IV
Intervention MeSH terms: Vidarabine; Cyclophosphamide; Fludarabine; Fludarabine phosphate
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase I trial studies side effects and best dose of PSCA-chimeric antigen receptor (CAR)
      T cells in treating patients with prostate stem cell antigen positive (PSCA+) castration
      resistant prostate cancer that has spread to other places in the body (metastatic). PSCA-CAR
      T cells are immune cells that have been engineered in the laboratory to kill tumor cells.
      This is done by using a virus to insert a piece of deoxyribonucleic acid (DNA) into the
      immune cells that allows them to recognize prostate tumor cells. It is not yet known how well
      PSCA-CAR T cells works in killing tumor cells in patients with metastatic castration
      resistant prostate cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  All participants must have the ability to understand and the willingness to sign a
             written informed consent

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2.

          -  Documented castration resistant prostate cancer (mCRPC) (Note: castration will be
             defined by a testosterone < 50 ng/dL achieved by orchiectomy or luteinizing
             hormone-releasing hormone [LHRH] agonist/antagonist therapy)

               -  Documented PSCA+ tumor expression as evaluated by City of Hope (COH) Pathology
                  Care

               -  Progression of disease manifest by one of the following means during treatment
                  with at least one advanced androgen targeted therapy (e.g., abiraterone or
                  enzalutamide)

                    -  Rising PSA documented on 2 occasions at least 7 days apart, with absolute
                       increase > 2 ng/dL despite testosterone < 50 OR

                    -  Radiographic evidence of new metastatic foci on computed tomography (CT) or
                       bone scan, or soft tissue progression by Response Evaluation Criteria in
                       Solid Tumors (RECIST)

          -  Prior chemotherapy with cabazitaxel and/or docetaxel is allowed but not required. If
             there has been prior chemotherapy, at least 2 weeks must have elapsed prior to
             leukapheresis

          -  Prior radiotherapy is allowed provided it was not administered to the only evaluable
             site of disease and was > 14 days prior to leukapheresis

          -  No known contraindications to leukapheresis, steroids or tocilizumab

          -  Total serum bilirubin =< 2.0 mg/dL (to be performed within 42 days of signing the main
             study consent)

               -  Patients with Gilbert syndrome may be included if their total bilirubin is =< 3.0
                  x upper limit of normal (ULN) and direct bilirubin =< 1.5 x ULN

          -  Aspartate aminotransferase (AST) < 3 x ULN (to be performed within 42 days of signing
             the main study consent)

          -  Alanine aminotransferase (ALT) < 3 x ULN (to be performed within 42 days of signing
             the main study consent)

          -  Creatinine clearance of >= 50 mL/min per the Cockcroft-Gault formula (to be performed
             within 42 days of signing the main study consent)

          -  Cardiac function (12 lead-electrocardiography [ECG]) (to be performed within 42 days
             of signing the main study consent)

          -  Left ventricular ejection fraction > 40% (to be performed within 42 days of signing
             the main study consent)

          -  Participants of reproductive potential must agree to use acceptable birth control
             methods throughout study therapy and for 3 months after final dose of study treatment

        Exclusion Criteria:

          -  Participants with clinically significant arrhythmia or arrhythmias not stable on
             medical management within two weeks of signing the main consent

          -  Participants 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 or other agents used in this study

          -  Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia

          -  History of stroke or intracranial hemorrhage within 6 months prior to signing the main
             consent

          -  History of other malignancies, except for malignancy surgically resected (or treated
             with other modalities) with curative intent, basal cell carcinoma of the skin or
             localized squamous cell carcinoma of the skin; non-muscle invasive bladder cancer;
             malignancy treated with curative intent with no known active disease present for >= 3
             years

          -  Uncontrolled active infection

          -  Active hepatitis B or hepatitis C infection

          -  Human immunodeficiency virus (HIV) infection

          -  Any other condition that would, in the investigator's judgment, contraindicate the
             subject'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)