RecruitingEarly Phase 1NCT06228404

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

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

Sponsor

Shanghai Changzheng Hospital

Enrollment

18 participants

Start Date

Mar 3, 2024

Study Type

INTERVENTIONAL

Conditions

Metastatic Castration-resistant Prostate Cancer Castration-resistant Prostate Cancer

Summary

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.

Eligibility

Sex: MALEMin Age: 18 YearsMax Age: 75 Years

Inclusion Criteria8

Fully understood and voluntarily signed informed consent for this study;
male, aged 18-75 years;
expected survival of more than 6 months;
metastatic castration-resistant prostate adenocarcinoma (CRPC) patients.
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);
PSMA expression in tumor cells was positive in immunohistochemical staining of prostate/metastatic biopsy tissue before enrollment;
ECOG score \< 2 ;
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 Criteria11

have received any previous treatment with CAR-T therapy ;
have received any previous treatment that targets PSMA;
tumor pathology suggests a special type of prostate cancer (e.g., neuroendocrine prostate cancer, etc.)
severe mental disorders;
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.
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;
active infectious disease or any major infectious event requiring high grade antibiotics;
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;
participation in other clinical studies in the past three months or previous treatment with any gene therapy product;
intolerance or hypersensitivity to cyclophosphamide and fludarabine chemotherapy;
unsuitability to participate in this clinical study in the opinion of the investigator.

Interventions

DRUGEnhanced 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;