This phase I trial tests the safety, side effects, best dose and how well giving IL-18 armored STEAP1 CAR T cells after lymphodepleting chemotherapy (with cyclophosphamide and fludarabine) works for the treatment of castration resistant prostate cancer that has spread from where it first started (primary site) to other places in the body (metastatic). Giving chemotherapy, with cyclophosphamide and fludarabine, prior to CAR T cells helps kill cancer cells in the body and prepare the body to receive the CAR T cells. Chimeric antigen receptor (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. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. Giving IL-18 armored STEAP1 CAR T cells after lymphodepleting chemotherapy may be safe, tolerable and/or effective in treating patients with metastatic castration resistant prostate cancer.
OUTLINE: Patients undergo leukapheresis. Patients receive cyclophosphamide intravenously (IV) and fludarabine IV on days -5 to -3. Patients receive FH-STEAP1 IL-18 CAR T cell IV on day 0. Patients may continue to receive androgen deprivation therapy per standard of care, throughout the study. Patients undergo nuclear medicine bone scan, computed tomography (CT) scan, magnetic resonance imaging (MRI) and/or positron emission tomography (PET) scan, tumor biopsy and blood sample collection throughout the study. Patients may also undergo multigated acquisition (MUGA) scan or echocardiography during screening. After completion of study treatment, patients are followed up on day +1, +3, +7, +10, +14, +21, + 28, months 2-6, month 9, month 12, then every 6 months until year 5 then yearly until year 15.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Given FH-STEAP1 IL-18 CAR T cells IV
Receive standard of care androgen deprivation therapy
Undergo blood sample collection
Undergo nuclear medicine bone scan
Undergo CT scan
Given IV
Undergo echocardiography
Given IV
Undergo leukapheresis
Undergo MRI
Undergo MUGA scan
Undergo PET scan
Undergo tumor biopsy
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
Treatment-related unexpected grade 3 or higher toxicity
Time frame: Up to 28 days post infusion
Incidence of adverse events
Time frame: Up to 28 days post infusion
Prostate cancer response
Assessed by Prostate Cancer Working Group 3 (PCWG3) criteria.
Time frame: Up to 1 year post infusion
Progression free survival
Will be analyzed using Kaplan-Meier method and the results will be summarized by the median with a 95% confidence interval if appropriate.
Time frame: From initiation of protocol treatment to disease progression or death of any cause, up to 1 year post infusion
Overall survival
Will be analyzed using Kaplan-Meier method and the results will be summarized by the median with a 95% confidence interval if appropriate.
Time frame: From initiation of protocol treatment to death of any cause, up to 1 year post infusion
Objective response rate
Defined as complete response or partial response by Response Evaluation Criteria in Solid Tumors 1.1 criteria and PCWG 3.
Time frame: Up to 1 year post infusion
Stable disease
Assessed by RECIST 1.1 criteria and PCWG3.
Time frame: Up to 1 year post infusion
Clinical benefit
Defined as overall response and stable disease assessed by RECIST 1.1 criteria and PCWG3.
Time frame: Up to 1 year post infusion
Overall response
Assessed by immune RECIST criteria.
Time frame: Up to 1 year post infusion
Prostate specific antigen (PSA) response
Defined as ≥ 50% reductions in PSA. The estimation with an exact 95% confidence interval will be provided.
Time frame: From baseline, up to 15 years
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