This phase I trial studies the side effects and best dose of autologous CD8+ and CD4+ lentivirally transduced to express L1CAM-specific chimeric antigen receptor (CAR) and EGFRt mutation specific T cells and to see how well they work in treating patients with small cell neuroendocrine prostate cancer (SCNPC) that has spread to nearby tissue or lymph nodes (locally advanced) and cannot be removed by surgery (unresectable) or has spread from where it first started (primary site) to other places in the body (metastatic). 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 tumor 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 tumor cells is added to the T cells in the laboratory. Some solid tumor cells have an L1CAM protein on their surface, and T cells can be modified with a receptor, called a chimeric antigen receptor (CAR), to help recognize this protein and kill these tumor cells. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. These L1CAM mutation specific T cells may help the body's immune system identify and kill L1CAM locally advanced and unresectable or metastatic small cell neuroendocrine prostate cancers' tumor cells.
OUTLINE: This is a dose-escalation study of autologous L1CAM-specific CAR+EGFRt+ T cells. Patients undergo leukapheresis to obtain peripheral blood mononuclear cells (PBMCs) for T cell product manufacturing and may undergo bridging therapy at the discretion of the treating clinician on study. Patients then undergo lymphodepleting chemotherapy with cyclophosphamide intravenously (IV) and fludarabine IV on days -5, -4 and -33 or single agent bendamustine on days -4 and -3 at the discretion of the treating clinician and/or principal investigator (PI). Patients receive an autologous L1CAM-specific CAR+EGFRt+ T cell infusion on day 0. Based on disease response and persistence of CAR T cells, patients may receive additional lymphodepletion chemotherapy and an autologous L1CAM-specific CAR+EGFRt+ T cell infusion as soon as 6 weeks and no later than 24 weeks after the first infusion, or at the discretion of the PI. Patients undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) during screening. Patients undergo x-ray imaging, computed tomography (CT), bone scan, and blood sample collection throughout the trial. Additionally, patients may undergo tissue biopsy on the trial. After completion of study treatment, patients are followed up monthly for 3 months, then every 3 months up to 12 months then may undergo long-term follow-up annually for up to 15 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Given IV
Undergo tissue biopsy
Undergo blood sample collection
Undergo bone scan
Undergo bridging therapy
Undergo CT
Given IV
Undergo ECHO
Given IV
Undergo leukapheresis
Undergo MUGA
Given autologous L1CAM-specific CAR+EGFRt+ T cells IV
Undergo chest x-ray
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
Incidence of adverse events
The toxicities observed at each dose level will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0 and nadir or maximum values for the laboratory measures), date of onset and attribution. Tables will be created to summarize these toxicities and side effects by dose level.
Time frame: Up to 12 months after last chimeric antigen receptor (CAR) T cell infusion
Dose-limiting toxicity rates
The toxicities observed at each dose level will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by NCI CTCAE version 5.0 and nadir or maximum values for the laboratory measures), date of onset and attribution. Tables will be created to summarize these toxicities and side effects by dose level.
Time frame: Within 28 days of last CAR T cell infusion
Objective response
Will be determined using RECIST version 1.1 and will be summarized at each dose level, and the number and percent responding combined across dose levels.
Time frame: Up to 12 months after last CAR T cell infusion
Radiographic progression free survival
Will be assessed using RECIST v 1.1 criteria for soft tissue metastases and Prostate Cancer Working Group 3 criteria. Survival and time to relapse/progression will be summarized both by pooling across dose levels and within each dose level. Will calculate survival curves and the median expected survival duration, using the Kaplan-Meier estimate.
Time frame: Up to 12 months after last CAR T cell infusion
Overall survival
Will be assessed using RECIST v 1.1 criteria for soft tissue metastases and Prostate Cancer Working Group 3 criteria. Survival and time to relapse/progression will be summarized both by pooling across dose levels and within each dose level. Will calculate survival curves and the median expected survival duration, using the Kaplan-Meier estimate.
Time frame: Up to 12 months after last CAR T cell infusion
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