Phase I Study of CART-PSMA Cells in Patients With Advanced Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Occurrence of study related adverse events, laboratory toxicities and clinical events that are possibly, likely, or definitely related to study participation.
研究概览
简要总结
This is a single center, open-label phase 1 study to assess the safety and feasibility of PSMA-specific CAR modified autologous T cells (CART-PSMA cells) in patients with advanced prostate cancer.
详细描述
Part A (Dose Escalation) + Part B (Expansion Cohort) total up to 20 patients enrolled.
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
- 35 Years 至 85 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •All participants must have the ability to understand and the willingness to sign a written informed consent.
- •Histologic confirmation of prostate cancer.
- •Tumor expressing PSMA as demonstrated by immunohistochemistry analysis or other methods.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 -
- •Under general air conditions, blood oxygen saturation >90%.
- •Adequate liver function, specifically alanine aminotransferase (ALT) < 3 times of upper limit of normal (ULN), aspartate transferase (AST)< 3 times of ULN, serum bilirubin and alkaline phosphatase < 2 times of ULN.
- •Adequate renal function, specifically serum creatinine < 2.0 mg/dl.
- •Adequate cardiac function, specifically left ventricular ejection fraction (LVEF)≥50%.
- •Hemoglobin concentration ≥80g/L.
- •The side effects brought by the latest treatment should be recovered, and the latest chemotherapy should be at least 7 days before; At least three t½ have passed since the latest immunotherapy.
排除标准
- •Patients with other malignant tumors or major diseases.
- •Patients who are already undergoing other clinical drug trials or other gene therapy or cell therapy.
- •Patients with uncontrolled active infection.
- •Patients with active hepatitis B or hepatitis C infection.
- •Patients with human immunodeficiency virus (HIV) infection.
- •Patients who are being treated with immunosuppressive agents or systemic steroids (other than inhalation therapy).
- •Patients with various types of serious heart disease or a history of severe cerebrovascular disease.
- •Patients with congenital immune deficiency diseases or bone marrow deficiency diseases.
- •Patients with active autoimmune disease, including connective tissue disease, uveitis, inflammatory bowel disease, or multiple sclerosis; or a history of severe (as judged by the physician-investigator) autoimmune disease requiring prolonged immunosuppressive therapy.
- •Patients with active medical condition that, in the opinion of the physician-investigator, would substantially increase the risk of uncontrollable CRS (cytokine release syndrome) or CAR Neurotoxicity.
研究组 & 干预措施
autologous CART-PSMA cells
Cohort 1： CART-PSMA cells 1-3x10^7/M^2(body surface area) on Day 0; Cohort 2： CART-PSMA cells 1-3x10^8/M^2(body surface area) on Day 0; Cohort 3： Lymphodepletion chemotherapy with fludarabine (30 mg/m2 body surface area) plus cyclophosphamide (300 mg/m2 body surface area) for 3 consecutive days during D-7 to D-3, followed by the infusion of CART-PSMA cells at 1-3x10^7/M^2(body surface area) on Day 0.
Cohort 4： Lymphodepletion chemotherapy with fludarabine (30 mg/m2 body surface area) plus cyclophosphamide (300 mg/m2 body surface area) for 3 consecutive days during D-7 to D-3, followed by the infusion of CART-PSMA cells at 1-3x10^8/M^2(body surface area) on Day 0.
干预措施: CART-PSMA cells (Drug)
结局指标
主要结局
Occurrence of study related adverse events, laboratory toxicities and clinical events that are possibly, likely, or definitely related to study participation.
时间窗: Up to 15 years
Assessing the type, frequency, severity, and duration of adverse events as a result of CART-PSMA cell infusion via physical, laboratory and imaging examination.
次要结局
- The persistence, accumulation, and migration of CART-PSMA cells.(Up to 2 years)
- Overall survival (OS)(Up to 15 years)
- Serum cytokine profile(Up to 2 years)
- Phenotypes and frequencies of immune cell subsets in the peripheral blood pre- and post-therapy(Up to 2 years)
- Progression-free survival (PFS)(Up to 15 years)
- Circulating cell-free deoxyribonucleic acid (cfDNA) in peripheral blood(Up to 2 years)
- Patterns of change in PSA (prostate-specific antigen)(Up to 5 years)
- Changes in circulating tumor cells in peripheral blood(Up to 2 years)