Trial Title:
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
Condition:
Prostate Carcinoma
Prostate Small Cell Neuroendocrine Carcinoma
Stage III Prostate Cancer AJCC v8
Stage IV Prostate Cancer AJCC v8
Conditions: Official terms:
Carcinoma
Prostatic Neoplasms
Carcinoma, Neuroendocrine
Carcinoma, Small Cell
Cyclophosphamide
Bendamustine Hydrochloride
Fludarabine
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Bendamustine
Description:
Given IV
Arm group label:
Treatment (autologous L1CAM-specific CAR+EGFRt+ T cells)
Other name:
SDX-105
Intervention type:
Procedure
Intervention name:
Biopsy
Description:
Undergo tissue biopsy
Arm group label:
Treatment (autologous L1CAM-specific CAR+EGFRt+ T cells)
Other name:
BIOPSY_TYPE
Other name:
Bx
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Treatment (autologous L1CAM-specific CAR+EGFRt+ T cells)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Bone Scan
Description:
Undergo bone scan
Arm group label:
Treatment (autologous L1CAM-specific CAR+EGFRt+ T cells)
Other name:
Bone Scintigraphy
Intervention type:
Procedure
Intervention name:
Bridge Therapy
Description:
Undergo bridging therapy
Arm group label:
Treatment (autologous L1CAM-specific CAR+EGFRt+ T cells)
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT
Arm group label:
Treatment (autologous L1CAM-specific CAR+EGFRt+ T cells)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Drug
Intervention name:
Cyclophosphamide
Description:
Given IV
Arm group label:
Treatment (autologous L1CAM-specific CAR+EGFRt+ T cells)
Other name:
(-)-Cyclophosphamide
Other name:
2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
Other name:
Asta B 518
Other name:
B-518
Other name:
Carloxan
Other name:
Ciclofosfamida
Other name:
Ciclofosfamide
Other name:
Cicloxal
Other name:
Clafen
Other name:
Claphene
Other name:
CP monohydrate
Other name:
CTX
Other name:
CYCLO-cell
Other name:
Cycloblastin
Other name:
Cycloblastine
Other name:
Cyclophospham
Other name:
Cyclophosphamid monohydrate
Other name:
Cyclophosphamide Monohydrate
Other name:
Cyclophosphamidum
Other name:
Cyclophosphan
Other name:
Cyclophosphane
Other name:
Cyclophosphanum
Other name:
Cyclostin
Other name:
Cyclostine
Other name:
Cytophosphan
Other name:
Cytophosphane
Other name:
Cytoxan
Other name:
Fosfaseron
Other name:
Genoxal
Other name:
Genuxal
Other name:
Ledoxina
Other name:
Mitoxan
Other name:
Neosar
Other name:
Revimmune
Other name:
Syklofosfamid
Other name:
WR- 138719
Other name:
WR-138719
Intervention type:
Procedure
Intervention name:
Echocardiography
Description:
Undergo ECHO
Arm group label:
Treatment (autologous L1CAM-specific CAR+EGFRt+ T cells)
Other name:
EC
Intervention type:
Drug
Intervention name:
Fludarabine
Description:
Given IV
Arm group label:
Treatment (autologous L1CAM-specific CAR+EGFRt+ T cells)
Other name:
Fluradosa
Intervention type:
Procedure
Intervention name:
Leukapheresis
Description:
Undergo leukapheresis
Arm group label:
Treatment (autologous L1CAM-specific CAR+EGFRt+ T cells)
Other name:
Leukocytopheresis
Other name:
Therapeutic Leukopheresis
Intervention type:
Procedure
Intervention name:
Multigated Acquisition Scan
Description:
Undergo MUGA
Arm group label:
Treatment (autologous L1CAM-specific CAR+EGFRt+ T cells)
Other name:
Blood Pool Scan
Other name:
Equilibrium Radionuclide Angiography
Other name:
Gated Blood Pool Imaging
Other name:
Gated Heart Pool Scan
Other name:
MUGA
Other name:
MUGA Scan
Other name:
Multi-Gated Acquisition Scan
Other name:
Radionuclide Ventriculogram Scan
Other name:
Radionuclide Ventriculography
Other name:
RNVG
Other name:
SYMA Scanning
Other name:
Synchronized Multigated Acquisition Scanning
Intervention type:
Biological
Intervention name:
T-cell Receptor-engineered T-cells
Description:
Given autologous L1CAM-specific CAR+EGFRt+ T cells IV
Arm group label:
Treatment (autologous L1CAM-specific CAR+EGFRt+ T cells)
Other name:
T-cell Receptor-engineered T Cells
Other name:
T-cell Receptor-engineered T-lymphocytes
Other name:
TCR T Cells
Other name:
TCR T-cells
Other name:
TCR-engineered T-cells
Other name:
TCR-modified T Cells
Intervention type:
Procedure
Intervention name:
X-Ray Imaging
Description:
Undergo chest x-ray
Arm group label:
Treatment (autologous L1CAM-specific CAR+EGFRt+ T cells)
Other name:
Conventional X-Ray
Other name:
Diagnostic Radiology
Other name:
Medical Imaging, X-Ray
Other name:
Plain film radiographs
Other name:
Radiographic Imaging
Other name:
Radiographic imaging procedure (procedure)
Other name:
Radiography
Other name:
RG
Other name:
Static X-Ray
Other name:
X-Ray
Summary:
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:
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.
Criteria for eligibility:
Criteria:
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
Gender:
Male
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Fred Hutch/University of Washington Cancer Consortium
Address:
City:
Seattle
Zip:
98109
Country:
United States
Contact:
Last name:
Fred Hutch Intake
Phone:
206-606-1024
Email:
hutchdoc@fredhutch.org
Investigator:
Last name:
Michael Schweizer
Email:
Principal Investigator
Start date:
April 15, 2025
Completion date:
March 15, 2028
Lead sponsor:
Agency:
Fred Hutchinson Cancer Center
Agency class:
Other
Collaborator:
Agency:
Bristol-Myers Squibb
Agency class:
Industry
Source:
Fred Hutchinson Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06094842
