Allogeneic B7-H3 CAR-γδT Cell Therapy Recurrent/Progressive High Grade Glioma（R/R HGG）
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Phase 1: Incidence of Adverse Events (AEs)
研究概览
简要总结
B7-H3 is expressed at low levels in normal tissues but overexpressed in various tumor tissues. The ubiquitous expression of B7-H3 in tumors of different grades is a key feature for brain gliomas. The immunohistochemistry study showed that B7-H3 is abundantly expressed on both glioma (especially high-grade glioma) cells and tumor-associated endothelial cells. For GBM, the expression of B7-H3 is intensely positive, especially on tumor cells and vascular endothelial cells, which makes B7-H3 a potential immunotherapeutic target.
γδ T cells recognize tumor cells without being restricted by MHC molecules, and thus can be used in allogeneic therapy without the risk of causing graft-versus-host disease.
This study is an open-label, single-arm, dose-escalation and dose-expansion clinical study aimed at evaluating the safety and efficacy of allogeneic B7-H3 CAR γδT in patients with malignant glioma.
详细描述
γδT cells are known as "a great candidate for car-t cells". Although they only account for 2% - 5% of all T cells in our body, they are a natural killer.
Treatment on this study includes six B7H3 CAR-γδ Tcell infusions over an 12 week period. B7H3 CAR-γδ T cells will be locoregionally administered via a CNS reservoir catheter without lymphodepleting chemotherapy. The study will evaluate the safety, feasibility and maximum tolerated dose (MTD) of B7H3 CAR-γδ T cell using a 3+3 study design and an 4 week evaluation period. The total study duration will be 2 years.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-70 years old (both ends included), both male and female;
- •At least one evaluable lesion, with previous biopsy or histopathological confirmation of high-grade glioma (WHO grade 3-4), and after comprehensive treatment, imaging examination indicates continued progression or recurrence;
- •The pathological tissues removed by surgery can be used for immunohistochemical detection of target proteins (paraffin sections should be within half a year), and the expression of B7-H3 is positive;
- •KPS ≥ 60 points;
- •Expected survival > 3 months;
- •Substantially normal bone marrow reserve function and normal liver and renal function (laboratory tests need to be fulfilled before receiving QH104 Cell Injection for the first time):White blood cell count (WBC) ≥ 3 x 10^9/L;Lymphocyte count (LY) ≥ 0.8 x 10^9/L;Hemoglobin (Hb) ≥ 90g/L;Platelet (PLT) ≥80×10^9/L;Albumin transaminase (ALT) & albumin transaminase (AST) <1.5×ULN;Serum creatinine (Cr) <1.5 x ULN;Total bilirubin < 1.5 x ULN;PT & PTT ≤ 1.25 x ULN.
- •No obvious hereditary diseases;
- •Normal cardiac function with cardiac ejection index >55%;
- •No bleeding and coagulation disorders;
- •Women of childbearing age (15-49 years old) must have had a pregnancy test with a negative result within 7 days prior to the start of treatment, and subjects are willing to use contraception during the clinical trial and for 3 months after the last cell infusion;
- •Sign the informed consent form.
排除标准
- •Pregnant and lactating women;
- •Those with organ failure:Heart: Class III and IV;Liver: up to grade C of the Child-Turcotte Liver -Function Classification;Kidney: chronic kidney disease stage 4 or above; renal insufficiency stage III or above;Lungs: symptoms of severe respiratory failure with involvement of other organs;Brain: central nervous system abnormalities or impaired consciousness;
- •patients with combined second tumors;
- •patients with active hepatitis B or C virus, HIV infection, or other untreated active infection;
- •any severe, uncontrolled systemic autoimmune disease or any unstable systemic disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, and temporal arteritis;
- •Current systemic use of steroid cell (except for recent or current use of inhaled steroids) substances;
- •have a chronic disease requiring immunologic or hormonal therapy;
- •have an allergy to immunotherapy and related cells;
- •10)Patients with a history of organ transplantation or who are awaiting organ transplantation;
- •Participation in other clinical trials within the previous 30 days;
- •Those who are not suitable for clinical trials for other reasons in the opinion of the investigator.
研究组 & 干预措施
Patients with R/R HGG
干预措施: Allogenic B7-H3 CAR-γδT cell(QH104) (Biological)
结局指标
主要结局
Phase 1: Incidence of Adverse Events (AEs)
时间窗: 12 months
AE is defined as any adverse medical event from the date of the cell infusion to 12 months after B7-H3 CAR-γδT cells infusion. Among them, cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS) were graded according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria, graft-versus-host disease (GVHD) according to criteria defined by the Mount Sinai Acute GVHD International Consortium. Other AEs were graded according to common terminology criteria for adverse events (CTCAE) v5.0.
Phase 1:Incidence of Dose-Limiting Toxicities (DLTs)
时间窗: 28 days after the first dose of B7-H3 CAR-γδT cells
DLT was defined as B7-H3 CAR-γδT cells-related events with onset within first 28 days following infusion
Phase 1:Maximum tolerated dose (MTD)
时间窗: 28 days after the first dose of B7-H3 CAR-γδT cells
Phase 1: Recommended phase 2 dose (RP2D)
时间窗: 28 days after the first dose of B7-H3 CAR-γδT cells
次要结局
- Pharmacokinetics: copy number of B7-H3 CAR-γδT cells in cerebrospinal fluid(CSF)(28 days after the first dose of B7-H3 CAR-γδT cells)
- Pharmacodynamics: Peak level of cytokines in CSF(28 days after the first dose of B7-H3 CAR-γδT cells)
- Phase 2: Overall survival (OS)(6 months, 9 months and 12 months)
- Phase 2: Progression Free Survival (PFS)(6 months)
- Disease Control Rate (DCR)(6 months)