The Safety and Efficacy Evaluation of Enhanced Autologous 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
- 18
- 试验地点
- 1
- 主要终点
- DLT
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 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 18-75 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.
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 > 2.5ULN; 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.
研究组 & 干预措施
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.
干预措施: Enhanced autologous PSMA-CAR T (Drug)
结局指标
主要结局
DLT
时间窗: Within 28 Days After Enhanced autologous PSMA-CAR T Infusion
The number and severity of dose-limiting toxicity (DLT) events
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
次要结局
- PSA response rate(From 3 weeks to 6 months after Enhanced autologous PSMA-CAR T infusion)
- ORR(6 months after Enhanced autologous PSMA-CAR T infusion)
- Efficacy assessment: PSA changes(6 months after CAR-T cell infusion)
- Efficacy assessment: radiographic Progression-Free Survival (rPFS)(3 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
Chief of Urology
Shanghai Changzheng Hospital