Autologous T Cells Lentivirally Transduced to Express L1CAM-Specific Chimeric Antigen Receptors in Treating Patients With Locally Advanced and Unresectable or Metastatic Small Cell Neuroendocrine Prostate Cancer

NCT ID: NCT06094842

Last Updated: 2025-04-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

WITHDRAWN

Clinical Phase

PHASE1

Study Classification

INTERVENTIONAL

Study Start Date

2025-04-15

Study Completion Date

2028-03-15

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Prostate Carcinoma Prostate Small Cell Neuroendocrine Carcinoma Stage III Prostate Cancer AJCC v8 Stage IV Prostate Cancer AJCC v8

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Treatment (autologous L1CAM-specific CAR+EGFRt+ T cells)

Patients undergo leukapheresis to obtain 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 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 PI. Patients receive an autologous L1CAM-specific CAR+EGFRt+ T cells 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 also undergo ECHO or MUGA during screening. Patients undergo x-ray imaging, CT, bone scan, and blood sample collection throughout the trial. Additionally, patients may undergo tissue biopsy on the trial.

Group Type EXPERIMENTAL

Bendamustine

Intervention Type DRUG

Given IV

Biopsy

Intervention Type PROCEDURE

Undergo tissue biopsy

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Bone Scan

Intervention Type PROCEDURE

Undergo bone scan

Bridge Therapy

Intervention Type PROCEDURE

Undergo bridging therapy

Computed Tomography

Intervention Type PROCEDURE

Undergo CT

Cyclophosphamide

Intervention Type DRUG

Given IV

Echocardiography

Intervention Type PROCEDURE

Undergo ECHO

Fludarabine

Intervention Type DRUG

Given IV

Leukapheresis

Intervention Type PROCEDURE

Undergo leukapheresis

Multigated Acquisition Scan

Intervention Type PROCEDURE

Undergo MUGA

T-cell Receptor-engineered T-cells

Intervention Type BIOLOGICAL

Given autologous L1CAM-specific CAR+EGFRt+ T cells IV

X-Ray Imaging

Intervention Type PROCEDURE

Undergo chest x-ray

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Bendamustine

Given IV

Intervention Type DRUG

Biopsy

Undergo tissue biopsy

Intervention Type PROCEDURE

Biospecimen Collection

Undergo blood sample collection

Intervention Type PROCEDURE

Bone Scan

Undergo bone scan

Intervention Type PROCEDURE

Bridge Therapy

Undergo bridging therapy

Intervention Type PROCEDURE

Computed Tomography

Undergo CT

Intervention Type PROCEDURE

Cyclophosphamide

Given IV

Intervention Type DRUG

Echocardiography

Undergo ECHO

Intervention Type PROCEDURE

Fludarabine

Given IV

Intervention Type DRUG

Leukapheresis

Undergo leukapheresis

Intervention Type PROCEDURE

Multigated Acquisition Scan

Undergo MUGA

Intervention Type PROCEDURE

T-cell Receptor-engineered T-cells

Given autologous L1CAM-specific CAR+EGFRt+ T cells IV

Intervention Type BIOLOGICAL

X-Ray Imaging

Undergo chest x-ray

Intervention Type PROCEDURE

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

SDX-105 BIOPSY_TYPE Bx Biological Sample Collection Biospecimen Collected Specimen Collection Bone Scintigraphy CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography CT CT Scan tomography (-)-Cyclophosphamide 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate Asta B 518 B-518 Carloxan Ciclofosfamida Ciclofosfamide Cicloxal Clafen Claphene CP monohydrate CTX CYCLO-cell Cycloblastin Cycloblastine Cyclophospham Cyclophosphamid monohydrate Cyclophosphamide Monohydrate Cyclophosphamidum Cyclophosphan Cyclophosphane Cyclophosphanum Cyclostin Cyclostine Cytophosphan Cytophosphane Cytoxan Fosfaseron Genoxal Genuxal Ledoxina Mitoxan Neosar Revimmune Syklofosfamid WR- 138719 WR-138719 EC Fluradosa Leukocytopheresis Therapeutic Leukopheresis Blood Pool Scan Equilibrium Radionuclide Angiography Gated Blood Pool Imaging Gated Heart Pool Scan MUGA MUGA Scan Multi-Gated Acquisition Scan Radionuclide Ventriculogram Scan Radionuclide Ventriculography RNVG SYMA Scanning Synchronized Multigated Acquisition Scanning T-cell Receptor-engineered T Cells T-cell Receptor-engineered T-lymphocytes TCR T Cells TCR T-cells TCR-engineered T-cells TCR-modified T Cells Conventional X-Ray Diagnostic Radiology Medical Imaging, X-Ray Plain film radiographs Radiographic Imaging Radiographic imaging procedure (procedure) Radiography RG Static X-Ray X-Ray

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Participants must be ≥ 18 years of age
* Able to understand and give written informed consent
* Confirmation of small cell neuroendocrine prostate cancer (SCNPC) diagnosis by internal pathology review of initial or subsequent biopsy or other pathologic material at Fred Hutchinson Cancer Center/University of Washington
* Previously treated with a platinum-based chemotherapy regimen for SCNPC
* Participants may not have received prior therapy or plan to receive therapy (chemotherapy, immunotherapy and/or radiation therapy) or have undergone or plan to undergo major surgery within the last 3 weeks prior to leukapheresis AND initiation of lymphodepleting chemotherapy. Participants who have developed SCNPC in the context of prior androgen deprivation therapy (ADT) (i.e. medical/surgical castration) may continue on ADT at the discretion of their treating provider
* Evidence of L1CAM positivity by immunohistochemistry review of the patient's archival/fresh tumor samples
* Metastatic or locally advanced and unresectable disease
* Adequate performance status (Eastern Cooperative Oncology Group \[ECOG\] 0 or 1)
* Expected survival \> 3 months
* Fertile participants must be willing to use an effective contraceptive method before, during, and for at least 4 months after the CAR T cell infusion
* Measurable disease per RECIST v1.1 criteria as determined by CT, MRI or positron emission tomography (PET) scan
* Hemoglobin \> 9 g/dL (prior to leukapheresis)
* Absolute neutrophil count (ANC) \> 1,500 per mm\^3 (prior to leukapheresis)
* Platelets \> 100,000 per mm\^3 (prior to leukapheresis)
* Creatinine ≤ 1.5 x upper limit of normal (ULN) (prior to leukapheresis)
* Bilirubin ≤ 1.5 x ULN (≤ 3 x ULN in patients with known Gilbert's syndrome) (prior to leukapheresis)
* Aspartate transaminase (AST) ≤ 3.0 x ULN (prior to leukapheresis)
* Alanine transaminase (ALT) ≤ 3.0 x ULN (prior to leukapheresis)
* Alkaline phosphatase ≤ 3.0 x ULN (prior to leukapheresis)
* All prior treatment related toxicity prior to leukapheresis ≤ grade 2 by National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version (v) 5.0

Exclusion Criteria

* Participants with non-melanoma skin cancer are eligible, while participants with other prior malignancies must have had at least a 3-year disease-free interval
* Participants with active human immunodeficiency virus (HIV) (testing not required per protocol but status noted). Participants with adequately treated HIV will be permitted to enroll. Adequately treated HIV will be defined as being on a stable regimen of highly active anti-retroviral therapy (HAART), CD4 count ≥ 350 cells/mcL, undetectable viral load on standard polymerase chain reaction (PCR)-based testing and not requiring antibiotics or antifungal agents for the prevention of opportunistic infections
* Participants with active hepatitis B (defined as hepatitis B surface antigen \[HBsAg\] reactive) or known active hepatitis C virus (defined as HCV RNA is detected) infection. Participants with prior hepatitis B virus (HBV) infection are eligible. Participants with a history of hepatitis C virus (HCV) infection are eligible if they have been treated with curative intent and their hepatitis C PCR viral load is negative
* Known history of unstable angina or myocardial infarction (MI) within 6 months or clinically significant cardiac arrhythmia (other than stable atrial fibrillation) requiring anti-arrhythmia therapy
* New York Heart Association (NYHA) class III or IV congestive heart failure (CHF), clinically significant hypotension, uncontrolled symptomatic coronary artery disease, or a documented ejection fraction of \< 35%
* Known history of clinically significant active chronic obstructive pulmonary disease (COPD), or other moderate-to-severe chronic respiratory illness present within 6 months
* Participants with clinically significant pulmonary dysfunction, as determined by medical history and physical exam should undergo pulmonary function testing. Those with an forced expiratory volume (FEV1) of \< 50 % of predicted or diffusing capacity for carbon monoxide (DLCO) (corrected) \< 40% will be excluded. Patients with \> grade 1 dyspnea at rest or oxygen saturation \< 94% on room air (resting)
* Infection requiring intravenous antibiotic use within 2 weeks of leukapheresis or uncontrolled active infection
* Baseline serum sodium level \< 130 mEq/L
* Research participant is not receiving systemically administered steroid therapy. Physiologic glucocorticoid replacement therapy for management of adrenal insufficiency is allowed (≤ 10 mg daily of prednisone or equivalent)
* History of an autoimmune disease requiring immunosuppressant therapy within the past 5 years
* Other concurrent medical or psychiatric conditions that, in the investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations
* Known history of brain metastases.

* Note: Brain imaging is not required to determine eligibility. However, this should be performed if there is clinical suspicion for brain metastases
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Bristol-Myers Squibb

INDUSTRY

Sponsor Role collaborator

Fred Hutchinson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Michael Schweizer

Role: PRINCIPAL_INVESTIGATOR

Fred Hutch/University of Washington Cancer Consortium

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

NCI-2023-07464

Identifier Type: REGISTRY

Identifier Source: secondary_id

FH20229

Identifier Type: OTHER

Identifier Source: secondary_id

RG1123589

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.