The Safety and Efficacy Evaluation of Universal PSMA Chimeric Antigen Receptor T Cells in the Treatment of Refractory Castration Resistant Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- The National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE V5.0)
研究概览
简要总结
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).
详细描述
This is a single-arm, single-center, open-label clinical trial, which aims to evaluate safety and clinical efficacy of different doses of PSMA-UCAR T (BRL-302) in treating patients with refractory CRPC.
Three patients will be firstly enrolled at a dose level (DL) of 5.0 × 10^6cells/kg in the DL1 group. 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Fully understood and voluntarily signed informed consent for this study;
- •Male, aged 18-80 years;
- •Expected survival of more than 6 months;
- •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;
- •PSMA expression in tumor cells was positive in immunohistochemical staining of prostate/metastatic biopsy tissue before enrollment (within 6 months prior to 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 × 10^9/L; c. neutrophils > 1.5 × 10^9/L.
排除标准
- •Subjects meeting any of the following exclusion criteria will be excluded:
- •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 > 2.5*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;
- •Participation in other clinical studies in the past three months or previous treatment with any gene therapy product;
- •Intolerance or hypersensitivity to cyclophosphamide or fludarabine chemotherapy;
- •Unsuitability to participate in this clinical study in the opinion of the investigator.
研究组 & 干预措施
PSMA-UCAR T (BRL-302)
干预措施: PSMA-UCAR T (BRL-302) (Biological)
结局指标
主要结局
The National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE V5.0)
时间窗: Through 6 months after CAR T cell infusion
Safety assessment: toxicity profile
Cytokine Release Syndrome (CRS) grading post CAR T cell infusion.
时间窗: Through 6 months after CAR T cell infusion
Safety assessment: toxicity profile
Safety assessment: dose-limiting toxicity
时间窗: 28 days after CAR T cell infusion
Incidence of dose-limiting toxicity (DLT) within 28 days. Dose-limiting toxicity (DLT) is defined as any relevant adverse event that ≥ grade 3 and did not resolve to a grade ≤ grade 2 within 28 days after the first infusion back.
次要结局
- Efficacy assessment: PSA changes(6 months after CAR T cell infusion)
- Efficacy assessment: radiographic Progression-Free Survival (rPFS)(6 months after CAR T cell infusion)
- 6-months Progression-Free Survival (PFS)(6 months after CAR T cell infusion)
- Pharmacokinetics (PK) assessment: expansion of CAR T cells(From Day 1 till at least 3 months after CAR T cell infusion)
- Pharmacokinetics (PK) assessment: persistence of CAR T cells(From Day 1 till at least 3 months after CAR T cell infusion)
- Pharmacodynamics (PD) assessment eg. (Level of IL-6)(From Day 1 till at least 3 months after CAR T cell infusion)
研究者
Ren Shancheng
Professor, Chief of Urology
Shanghai Changzheng Hospital