A Phase I Study to Evaluate the Safety and Efficacy of PSMA-CART Co-expressing LIGHT in Treating Patients With Castrate-Resistant Prostate Cancer (CRPC)
试验速览
- 阶段
- 1 期
- 状态
- 暂停
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Incidence of toxicity graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03
研究概览
简要总结
This is a single center, single arm Phase I study to establish the safety and efficacy of intravenously administered lentivirally transduced LIGHT-PSMA-specific CAR modified autologous T cells (PSMA-CART cells) in patients with CRPC.
详细描述
This is a Phase I study evaluating the safety and efficacy of PSMA targeting autologous CAR T cells co-expressing LIGHT in a 3+3 dose escalation design. Cohort 1 subjects (N=3 or 6) will receive a tolal dose of 3x 10^6/kg body weight (KgBW) LIGHT-PSMA-CART cells at split doses after a conditioning chemotherapeutic regimen(Cy+Flu). If 1 DLT/3 subjects occurs, the study will enroll an additional 3 subjects at this dose level. If 0 DLT/3 subjects or 1 DLT/6 subjects occurs, the study will advance to Cohort 2, with a total dose of 6 x 10^6/ KgBW.
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 understand and voluntarily sign informed consent.
- •Male, aged 18 to 75 years old.
- •Expected survival > 6 months.
- •CRPC patients: Prostate cancer is still progressing after continuous androgen deprivation therapy. Including, castrate levels of serum testosterone (<50ng/dl or <1.7nmol/L); or prostate specific antigen (PSA) increased more than 50% at intervals of one week or three consecutive times, and PSA>1 ug/L; or imaging scans revealed two or more new lesions or enlargement of soft tissue lesions that met the criteria for evaluating solid tumor response.
- •CRPC patients received abiraterone or chemotherapy for 3 months or more, and were ineffective or progressive (PSA continued to rise for 3 months, or bone scan/whole-body MRI/PET-CT showed local recurrence or new metastasis).
- •Immunohistochemical staining of repetitive biopsy tissues showed the expression of PSMA in tumor cells was more than 50%.
- •ECOG score <
- •Hgb > 10 g/dl.
- •PLT > 100×109/L.
- •ANC > 1.5×109/L.
排除标准
- •Subjects who meet any of the following exclusion criteria will be excluded
- •Prior treatment with any immunotherapy, including CART therapy, tumor vaccine therapy, radium-223, checkpoint inhibitors.
- •Prior treatment with any PSMA targeting therapy.
- •Subjects with severe mental disorders.
- •Subjects with severe cardiovascular diseases: a, New York Heart Association (NYHA) stage III or IV congestive heart failure; b, history of myocardial infarction or coronary artery bypass grafting (CABG) within 6 months; c, clinical significance of ventricular arrhythmia, or history of unexplained syncope, non-vasovagal or dehydration; d, history of severe non-ischemic cardiomyopathy; e, the left ventricular ejection fraction (LVEF < 55%) was decreased by echocardiography or MUGA scan (within 8 weeks before PBMC collection), and abnormal interventricular septal thickness and atrioventricular size associated with myocardial amyloidosis.
- •Patients with ongoing or active infection.
- •Aspartate aminotransferase or Alanine aminotransferase >2.5*ULN; CK>1.5*ULN; CK-MB>1.5*ULN; TnT>1.5*ULN.
- •Total bilirubin >1.5*ULN.
- •Partial prothrombin time or activated partial thromboplastin time or international standardized ratio > 1.5*ULN without anticoagulant treatment.
- •History of participation in other clinical studies within 3 months or treatment with any gene therapy product.
- •Intolerant or allergic to cyclophosphamide or fludarabine.
- •Subjects not appropriate to participate in this clinical study judged by investigators.
结局指标
主要结局
Incidence of toxicity graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03
时间窗: 28 days
All adverse events (AEs) will be listed and summarized. Summaries of laboratory data will include, at a minimum, treatment-emergent laboratory abnormalities. Summaries of AEs and laboratory abnormalities will be based on the All Treated analysis set.
次要结局
- Radiographic response rate by RECIST 1.1 & PCWG3.(24 weeks)
- PSA response rate(24 weeks)
- Duration time of CART cells in vivo(24 weeks)