NCT03941626Unknown1 期
EGFRvIII/DR5/NY-ESO-1/Mesothelin CAR-T/TCR-T Cells Immunotherapy for Solid Malignancies
Shenzhen BinDeBio Ltd.1 个研究点 分布在 1 个国家目标入组 50 人开始时间: 2019年9月1日最近更新:
适应症
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Number of Participants With Adverse Events evaluated with NCI CTC AE, version 4.0
研究概览
简要总结
This is a single arm, open-label, uni-center, phase I-II study to evaluate the safety and effectiveness of CAR-T/TCR-T cell immunotherapy in treating with different malignancies patients.
详细描述
The study is a multi-target gene-modified immunotherapy. CAR-T/TCR-T cells include four different tumor-specific antibody.They are as following:anti-NY-ESO-1 antibody foresophagus cancer;anti-DR5 antibody for hepatoma;;anti-EGFR vIII antibody for hepatoma and glioma;anti-Mesothelin antibody for gastric cancer.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must be willing to sign an informed consent.
- •Male or female patients aged 18 to 70 years .
- •Estimated survival of ≥ 12 weeks.
- •Pathological sections with positive expression of NY-ESO-1, Mesothelin, EGFRvIII and DR5 was confirmed by biopsy IHC test within 12 months.If NY-ESO-1 is positive expression ,positive HLAA*0201 is required at the same time.
- •Solid tumor must have at least one measureable disease according to RECIST 1.
- •Routine blood test#hemoglobin>=90 g/L; platelet>=50×10^9/L.
- •Liver function:ALT and AST≤2.5 times upper limits of normal (If the tumor infiltration is the main cause of abnormal liver function ,ALT and AST≤5 times upper limits of normal); bilirubin<2.0 mg/dL.
- •Renal function:BUN: 9-20mg / dl; serum creatinine≤ 1.5 times upper limits of normal; endogenous creatinine clearance rate≥50 ml/min .
- •Negative serum antibody for EBV, CMV, HIV , syphilis, HBVa nd HCV.
- •Cardiac function: stable hemodynamic and left ventricular ejection fraction (LVEF)>=55%.
- •ECOG score:0-
- •Adequate venous access for apheresis, and no other contraindications for leukapheresis .
- •Women of child-bearing age must have evidence of negative pregnancy test. Subjects of reproductive potential must agree to use acceptable birth control methods within 1 year after treatment, as described in protocol.
- •Subjects with hypertension/diabetes must be stable blood pressure/blood glucose or ≤CTCAE 1 level 2 weeks before the screening.
- •In addition to the above criteria for inclusion, the following criteria shall be met according to the indications:
- •Patients with glioblastoma：
- •First disease progression or disease recurrence (≥ 1 cm and ≤ 5 cm) of a supratentorial WHO grade IV malignant glioma (GBM or gliosarcoma) based on imaging studies with measurable disease.
- •EGFRvIII, the target antigen, must be identified on tumor tissue by IHC or PCR, i.e. EGFRvIII positive via pathology report.
- •Insensitivity to chemoradiotherapy or chemoradiotherapy failure after operation molecular pathology.
- •Refused to receive radiotherapy or chemotherapy treatment.
- •Patients with liver cancer
- •DR5 or EGFRvIII positive via pathology report.
- •Untreatable by surgery ; Or postoperative recurrence ;Or no effective treatment.
- •Liver function：child-pugh A grade or child-pugh B grade.
- •Patients with gastric cancer
- •Mesothelin positive via pathology report.
- •The pathological stage：IIIA～IV.
- •chemoradiotherapy failure
- •Refused or unable to get surgery.
- •Patients with esophageal cancer
- •NY-ESO-1 positive via pathology report and HLA-A*0201 positive in blood.
- •Refuse or unable to get surgery.
- •Postoperative recurrence or chemoradiotherapy failure.
排除标准
- •malignant tumor cells with T cell origin via pathology test.
- •Organ failure: stage III or IV congestive heart failure; Renal failure and uremia; respiratory failure; disturbance of consciousness.
- •Acute or chronic GVHD after allogeneic hematopoiesis; Or being treated for GVHD; Or hormone or immunosuppressant used within 30 days
- •steroid hormoneswere used before and after blood collection and infusion
- •Patients with HIV infection or active hepatitis
- •Uncontrolled active infection.
- •Enrolled to other clinical study in the last 4 weeks.
- •Patients with systemic auto-immune disease or immunodeficiency.
- •Patients with neuropathy or psychosis, including dementia or epilepsy, or history of psychotropic substance abuse, or other substantial lesions that may increase central neurotoxicity.
- •Concomitant with the second tumor or other malignant tumors.
- •Patients with bone metastases are at risk of a pathological fracture resulting in paraplegia or life threatening.
- •Live attenuated vaccine was administered within 4 weeks prior to blood collection.
- •Blood oxygen saturation is maintained by oxygen inhalation.
- •Received major surgery within 2 weeks prior to screening ;Or Plan to receive surgery during study or within 2 weeks after injection.
- •Other patients that researchers considered unsuitable for inclusion.
结局指标
主要结局
Number of Participants With Adverse Events evaluated with NCI CTC AE, version 4.0
时间窗: 48 months
Safety evaluation
次要结局
- Clinical response(48 months)
研究者
研究点 (1)
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