A Clinical Study of CTLA-4 and PD-1 Antibodies Expressing MUC1-CAR-T Cells for Patients With MUC1 Positive Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Safety of infusion of autologous CTLA-4 and PD-1 antibodies expressing MUC1-targeted CAR-T cells
研究概览
简要总结
This is a single-arm, open-label, one center clinical study, to determine the safety and efficacy of infusion of autologous T cells engineered to express immune checkpoint antibodies (CTLA-4 and PD-1) and chimeric antigen receptor targeting MUC1 in adult patients with MUC1 positive, advanced recurrent or refractory malignant solid tumors.
详细描述
This study will be conducted using a phase I/II trial design to assess the safety and efficacy of the CTLA-4 and PD-1 antibodies expressing MUC1-CAR-T for patients with MUC1 positive, advanced recurrent or refractory malignant solid tumors. MUC1-CAR-T can specificly and effectively kill the MUC1 positive cancer cells, CTLA4 and PD-1 antibodies are secreted from the CAR-T cells could improve immunosuppression microenvironment, new CAR-T cells contain the advantages of CAR-T and immune checkpoint inhibitor, which is a promising therapeutic method for advanced solid tumors.
The new CAR-T therapy is applied to clinical practice as bellow. T cells are prepared from peripheral blood mononuclear cells (PBMC) by leukapheresis, and then activated and engineered to express CTLA-4 and PD-1 antibodies and chimeric antigen receptor targeting MUC1. Cells are proliferated in culture and returned to the patients by venous transfusion. A total of 40 patients may be enrolled in the study. The total duration of the study is expected to be approximately 24 months.
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
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with relapsed or refractory advanced solid malignancies (diagnosed by histology or cytology detection).
- •Progressive disease and no response after at least second-line therapy.
- •Gender unlimited, age from 18 years to 80 years.
- •Life expectancy≥3 months.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •Adequate venous access for peripheral blood mononuclear cell (PBMC) apheresis, and no other contraindications.
- •Immunohistochemistry (IHC) score of MUC1 on tumor tissue ≥1+.
- •Adequate hepatic function, renal function and bone marrow function (withhin 7 days before enrollment): white blood cell (WBC)≥3.0×10^9/L; platelet≥100×10^9/L; hemoglobin≥90 g/L; lymphocyte ≥0.7×10^9/L; total bilirubin ≤2 times the upper limit of the normal value; alanine aminotransferase and aspartate transaminase (ALT and AST) ≤2.5 times the upper limit of the normal value; serum creatinine ≤1.5 times the upper limit of the normal value.
- •There is no other treatments (chemotherapy, radiotherapy, etc.) within four weeks before enrollment.
- •There is at least one measurable tumor lesion.
- •Patients have adequate ability to understand, sign informed consents and take part in the clinical research voluntarily.
- •Female patients in child bearing period must have evidence of negative pregnancy test, and agree to take effective contraceptive measures until 4 months after cells infusion.
排除标准
- •Patients with two or more kinds of tumors.
- •Patients with active viral or bacterial infection, and have failed to be controlled by anti-infective treatment.
- •Patients with seropositive reponse of Human immunodeficiency virus (HIV) and syphilis, or fail to control the hepatitis B virus or hepatitis C virus infection.
- •Patients with active rheumatic diseases, organ transplantation and other diseases affecting the immune system seriously.
- •Patients with severe heart and lung dysfunction.
- •Patients with severe chronic diseases of kidney, liver and other important organs.
- •Patients with any other serious illnesse that the investigators consider it will may affect the patient's treatments, follow-up or assessment, including any uncontrolled clinically significant neurological or psychiatric disorders, immunoregulatory diseases, metabolic diseases, infectious diseases and so on.
- •Patients who take part in clinical trials of other drugs or biological therapy at present or within 30 days before enrollment.
- •Patients who need long-term use of immunosuppressive drugs or patients who are undergoing treatment of autoimmune diseases.
- •Patients who need long-term use of glucocorticoid.
- •Women patients in gestation period or suckling period.
结局指标
主要结局
Safety of infusion of autologous CTLA-4 and PD-1 antibodies expressing MUC1-targeted CAR-T cells
时间窗: 2 years
Determine the toxicity profile of CTLA4 and PD-1 antibodies expressing MUC1-targeted CAR-T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.
次要结局
- The efficacy of the treatment using CTLA-4 and PD-1 antibodies expressing MUC1-CAR-T cells for advanced solid tumors(2 years)