- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06094842
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
A Phase I Safety and Feasibility Study of Cellular Immunotherapy for Extensive Stage Small Cell Neuroendocrine Prostate Cancer Using Autologous T Cells Lentivirally Transduced to Express L1CAM-Specific Chimeric Antigen Receptor
Study Overview
Status
Conditions
Intervention / Treatment
- Procedure: Computed Tomography
- Procedure: Biospecimen Collection
- Drug: Cyclophosphamide
- Drug: Fludarabine
- Procedure: Leukapheresis
- Drug: Bendamustine
- Procedure: Echocardiography
- Procedure: Multigated Acquisition Scan
- Procedure: Biopsy
- Procedure: Bone Scan
- Procedure: X-Ray Imaging
- Procedure: Bridge Therapy
- Biological: T-cell Receptor-engineered T-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.
Study Type
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Fred Hutch Intake
- Phone Number: 206-606-1024
- Email: hutchdoc@fredhutch.org
Study Locations
-
-
Washington
-
Seattle, Washington, United States, 98109
- Fred Hutch/University of Washington Cancer Consortium
-
Principal Investigator:
- Michael Schweizer
-
Contact:
- Fred Hutch Intake
- Phone Number: 206-606-1024
- Email: hutchdoc@fredhutch.org
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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.
|
Undergo CT
Other Names:
Undergo blood sample collection
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Undergo leukapheresis
Other Names:
Given IV
Other Names:
Undergo ECHO
Other Names:
Undergo MUGA
Other Names:
Undergo tissue biopsy
Other Names:
Undergo bone scan
Other Names:
Undergo chest x-ray
Other Names:
Undergo bridging therapy
Given autologous L1CAM-specific CAR+EGFRt+ T cells IV
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of adverse events
Time Frame: Up to 12 months after last chimeric antigen receptor (CAR) T cell infusion
|
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.
|
Up to 12 months after last chimeric antigen receptor (CAR) T cell infusion
|
Dose-limiting toxicity rates
Time Frame: Within 28 days of last CAR T cell infusion
|
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.
|
Within 28 days of last CAR T cell infusion
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective response
Time Frame: Up to 12 months after last CAR T cell infusion
|
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.
|
Up to 12 months after last CAR T cell infusion
|
Radiographic progression free survival
Time Frame: Up to 12 months after last CAR T cell infusion
|
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.
|
Up to 12 months after last CAR T cell infusion
|
Overall survival
Time Frame: Up to 12 months after last CAR T cell infusion
|
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.
|
Up to 12 months after last CAR T cell infusion
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Michael Schweizer, Fred Hutch/University of Washington Cancer Consortium
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Adenocarcinoma
- Neoplasms, Glandular and Epithelial
- Genital Neoplasms, Male
- Prostatic Diseases
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Neuroendocrine Tumors
- Urogenital Diseases
- Male Urogenital Diseases
- Genital Diseases, Male
- Genital Diseases
- Prostatic Neoplasms
- Carcinoma
- Carcinoma, Neuroendocrine
- Carcinoma, Small Cell
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Cyclophosphamide
- Bendamustine Hydrochloride
- Fludarabine
Other Study ID Numbers
- RG1123589
- NCI-2023-07464 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- FH20229 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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