Clinical Study of Safety and Efficacy of Enhanced PSMA CAR- T in Refractory CRPC

April 17, 2024 updated by: Ren Shancheng, Shanghai Changzheng Hospital

The Safety and Efficacy Evaluation of Enhanced Autologous PSMA Chimeric Antigen Receptor T Cells in the Treatment of Refractory Castration Resistant Prostate Cancer

This is one center, single-arm, open-label investigator initiated trial to assess the safety and efficacy of enhanced autologous PSMA chimeric antigen receptor T cells in the treatment for patients with refractory castration resistant prostate cancer, and the sample size is set to 7-18 subjects.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is one center, single-arm, open-label investigator initiated trial to assess the safety and efficacy of enhanced autologous PSMA chimeric antigen receptor T cells in the treatment for patients with refractory castration resistant prostate cancer, and the sample size is set to 7-18 subjects. Based on the "3 + 3" dose escalation design principle, subjects will be divided into 3 groups from low dose to high dose in sequence (Group A; Group B; Group C). Additional subjects will be enrolled into the RP2D group to ensure that 6-9 efficacy-evaluable subjects are available in the RP2D group before entering the phase II study.

Study Type

Interventional

Enrollment (Estimated)

18

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Weidong Xu
  • Phone Number: 139 1687 9385
  • Email: ayxwd@qq.com

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 201109
        • Recruiting
        • Changzheng hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Fully understood and voluntarily signed informed consent for this study;
  2. male, aged 18-75 years;
  3. expected survival of more than 6 months;
  4. metastatic castration-resistant prostate adenocarcinoma (CRPC) patients.
  5. Receiving CRPC standard treatment (such as new endocrine therapy, chemotherapy and radium-223, etc., one or more of the combination therapy) after the diagnosis of CRPC, ineffective or progressive disease (PSA continued to rise for 3 months, or bone scan/whole-body MRI/PET-CT showed local recurrence or new metastatic lesions, demonstrating disease progression);
  6. PSMA expression in tumor cells was positive in immunohistochemical staining of prostate/metastatic biopsy tissue before enrollment;
  7. ECOG score < 2 ;
  8. virological examination HAV (hepatitis A virus), HBV (hepatitis B virus), HCV (hepatitis C virus), HIV (human immunodeficiency virus), TP (Treponema pallidum) quantitative detection was negative, (antigen and antibody screening method unknown, confirmed by nucleic acid method); hematological parameters met the following criteria: a. hemoglobin > 100 g/L; b. platelet count > 100 × 109/L; c. neutrophils > 1.5 × 109/L.

Exclusion Criteria:

Subjects meeting any of the following exclusion criteria will be excluded:

  1. have received any previous treatment with CAR-T therapy ;
  2. have received any previous treatment that targets PSMA;
  3. tumor pathology suggests a special type of prostate cancer (e.g., neuroendocrine prostate cancer, etc.)
  4. severe mental disorders;
  5. suffered from previous malignancies, except for the following: a. basal cell carcinoma or squamous cell carcinoma after standardized treatment; b. having a primary malignancy, but completely resected, with a complete remission time of ≥ 5 years.
  6. Subjects with severe cardiovascular disease; a.New York Heart Association (NYHA) stage III or IV congestive heart failure; b.Myocardial infarction ≤ 6 months prior to enrollment or coronary artery bypass graft (CABG); c.Clinically significant ventricular arrhythmia, or history of unexplained syncope, nonvasovagal or not due to dehydration; d.History of severe non-ischemic cardiomyopathy; e.Decreased left ventricular ejection fraction (LVEF < 55%) as assessed by echocardiogram or multigated acquisition (MUGA) scan, abnormal interventricular septal thickness and atrioventricular size associated with myocardial amyloidosis;
  7. active infectious disease or any major infectious event requiring high grade antibiotics;
  8. organ function in the following abnormalities: a. serum aspartate aminotransferase or alanine aminotransferase > 2.5ULN; CK > ULN; CK-MB > ULN; TnT > 1.5ULN; b. total bilirubin > 1.5ULN; c. partial prothrombin time or activated partial thromboplastin time or international normalized ratio > 1.5ULN in the absence of anticoagulant therapy;
  9. participation in other clinical studies in the past three months or previous treatment with any gene therapy product;
  10. intolerance or hypersensitivity to cyclophosphamide and fludarabine chemotherapy;
  11. unsuitability to participate in this clinical study in the opinion of the investigator.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Enhanced autologous PSMA-CAR T:
Enhanced autologous PSMA-CAR T is an electrotransfer system based on non-viral transposons that integrates the CAR gene into the genome of host cells by electrotransfer using PMSA as a target, while this CAR vector co-expresses enhanced factors and plays a strong regulatory role in innate and adaptive immunity.
Drug: Enhanced autologous PSMA-CAR T

3 escalated dosing cohorts are designed to explore safety and efficacy of enhanced autologous PSMA-CAR T:

cohort A： CART-PSMA cells 0.25×106/kgBW, following lymphodepleting chemotherapy with cyclophosphamide 300 mg/m2/day and fludarabine 30 mg/m2/day given according to protocol;

cohort B： CART-PSMA cells 0.75×106/kgBW，following lymphodepleting chemotherapy with cyclophosphamide 300 mg/m2/day and fludarabine 30 mg/m2/day given according to protocol;

cohort C： CART-PSMA cells 2×106/kgBW，following lymphodepleting chemotherapy with cyclophosphamide 300 mg/m2/day and fludarabine 30 mg/m2/day given according to protocol;

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
DLT
Time Frame: Within 28 Days After Enhanced autologous PSMA-CAR T Infusion
The number and severity of dose-limiting toxicity (DLT) events
Within 28 Days After Enhanced autologous PSMA-CAR T Infusion

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
PSA response rate
Time Frame: From 3 weeks to 6 months after Enhanced autologous PSMA-CAR T infusion
PSA50 response, PSA90 response: PSA response determined as ≥ 50% or ≥ 90% reduction in PSA level from baseline to post-baseline and reassessed at least 3 weeks later
From 3 weeks to 6 months after Enhanced autologous PSMA-CAR T infusion
ORR
Time Frame: 6 months after Enhanced autologous PSMA-CAR T infusion
Objective response rate ORR = CR + PR
6 months after Enhanced autologous PSMA-CAR T infusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shanghai Changzheng Hospital

Collaborators

Bioray Laboratories

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 3, 2024

Primary Completion (Estimated)

May 1, 2025

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

January 19, 2024

First Submitted That Met QC Criteria

January 19, 2024

First Posted (Actual)

January 29, 2024

Study Record Updates

Last Update Posted (Actual)

April 18, 2024

Last Update Submitted That Met QC Criteria

April 17, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2022-BRL-501

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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