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RECRUITINGPhase 1INTERVENTIONAL

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

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

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

This is a single-arm, single-center, open-label clinical trial designed to evaluate the clinical safety and tolerability of different doses of Prostate-Specific Membrane Antigen (PSMA)-Universal Chimeric Antigen Receptor (UCAR) T-lymphocytes (PSMA-UCAR T) for the treatment of patients with refractory castration-resistant prostate cancer (CRPC).

Who May Be Eligible (Plain English)

Who May Qualify: 1. Fully understood and voluntarily signed willing to sign a consent form for this study; 2. Male, aged 18-80 years; 3. Expected survival of more than 6 months; 4. Metastatic castration-resistant prostate adenocarcinoma (CRPC) patients: Have received CRPC standard treatment (such as novel hormone therapies, chemotherapy and radium-223, etc., one or more of the combination therapy) after the diagnosis of CRPC, and is ineffective or progressive :PSA continued rising for 3 months, or bone scan/whole-body MRI/PET-CT showed local recurrence or new metastatic lesions, demonstrating disease progression; 5. PSMA expression in tumor cells was positive in immunohistochemical staining of prostate/metastatic biopsy tissue before enrollment (within 6 months prior to enrollment); 6. ECOG score \< 2 ; 7. Virological examination HAV (hepatitis A virus), HBV (hepatitis B virus), HCV (hepatitis C virus), HIV (human weakened immune system virus), TP (Treponema pallidum) quantitative detection was negative, (antigen and antibody screening method unknown, confirmed by nucleic acid method); 8. Hematological parameters met the following criteria: a. hemoglobin \> 100 g/L; b. platelet count \> 100 × 10\^9/L; c. neutrophils \> 1.5 × 10\^9/L. Who Should NOT Join This Trial: 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. ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language
Inclusion Criteria: 1. Fully understood and voluntarily signed informed consent for this study; 2. Male, aged 18-80 years; 3. Expected survival of more than 6 months; 4. Metastatic castration-resistant prostate adenocarcinoma (CRPC) patients: Have received CRPC standard treatment (such as novel hormone therapies, chemotherapy and radium-223, etc., one or more of the combination therapy) after the diagnosis of CRPC, and is ineffective or progressive :PSA continued rising for 3 months, or bone scan/whole-body MRI/PET-CT showed local recurrence or new metastatic lesions, demonstrating disease progression; 5. PSMA expression in tumor cells was positive in immunohistochemical staining of prostate/metastatic biopsy tissue before enrollment (within 6 months prior to enrollment); 6. ECOG score \< 2 ; 7. 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); 8. Hematological parameters met the following criteria: a. hemoglobin \> 100 g/L; b. platelet count \> 100 × 10\^9/L; c. neutrophils \> 1.5 × 10\^9/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 \> 2.5\*Upper Limit of Normal (ULN); CK \> ULN; CK-MB \> ULN; TnT \> 1.5\*ULN; b. total bilirubin \> 1.5\*ULN; c. partial prothrombin time or activated partial thromboplastin time or international normalized ratio \> 1.5\*ULN 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 or fludarabine chemotherapy; 11. Unsuitability to participate in this clinical study in the opinion of the investigator.

Treatments Being Tested

BIOLOGICAL

PSMA-UCAR T (BRL-302)

Three patients will be firstly enrolled at a dose level (DL) of 5.0 × 10\^6cells/kg in the DL1 group, following lymphodepleting chemotherapy which will be given under instruction of protocol and investigators' assessment; Based on preliminary safety data, efficacy information, and PK/PD parameters obtained at DL1 cohort, the investigator may enroll another three patients in a decreased dose level group of DL-2: 3 × 10\^6 cells/kg or DL-1:1 × 10\^6 cells/ kg, after thorough discussions between the investigators.

Locations (1)

Changzheng hospital
Shanghai, Shanghai Municipality, China