Allogeneic Gamma Delta (γδ) T Cells for the Treatment of Glioblastoma
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 18
- 试验地点
- 3
- 主要终点
- Incidence of Adverse Events (AEs)
研究概览
简要总结
This first-in-human clinical study aims to evaluate the safety and feasibility of locally delivered, allogeneic γδ T cells (genetically edited with ARIH1 and BCL11b knockout, designated ABOUT γδT cells) in patients with glioblastoma multiforme (GBM). The engineered effector cells are delivered via localized administration to selectively target and eliminate residual GBM cells. ABOUT: ARIH1 and BCL11b knockOUT γδ T cells.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Male or female, age 18-70 years old (both ends included)
- •At least one evaluable lesion with previous biopsy or pathohistologic confirmation of glioblastoma (WHO grade IV), with imaging suggestive of continued progression or recurrence after comprehensive treatment
- •Karnofsky Performance Status (KPS) ≥ 60%
- •Life expectancy > 4 weeks
- •Patients who completed radiotherapy or systemic therapies (including temozolomide/bevacizumab or other agents) for at least 4 weeks prior to enrollment. All prior treatment-related toxicities should be defined as ≤ grade 1 (except for toxicities such as alopecia or leukoplakia) according to the Common Terminology Standard for Adverse Events (CTCAE 6.0)
- •Must be able to undergo an MRI with contrast
- •Must have adequate organ and marrow function as defined below:
- •White blood cell count (WBC) ≥ 3 x 10^9/L
- •Absolute neutrophil count (ANC) > 1 x 10^9/L
- •Hemoglobin (Hb) ≥ 90 g/L
- •Platelet (PLT) ≥ 80×10^9/L
- •Albumin transaminase (ALT) & albumin transaminase (AST) < 1.5 × institutional upper limit of normal (ULN)
- •Serum creatinine (Cr) < 1.5 x institutional ULN
- •Total bilirubin < 1.5 x institutional ULN
- •PT & PTT ≤ 1.25 x institutional ULN
- •No obvious hereditary diseases
- •Normal cardiac function with left ventricular ejection fraction >55%
- •No bleeding and coagulation disorders
- •Absence of positive blood cultures for bacteria, fungus, or virus within 48-hours prior to ABOUT γδT cell infusion and/or there aren't any indications of meningitis
- •Fertile women 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 (hormonal or barrier method of birth control or abstinence) during the clinical trial and for 6 months after the last cell infusion; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
- •Signed, written informed consent
排除标准
- •Active hepatitis B or C virus, HIV infection, or other untreated active infection
- •Pregnant and lactating women
- •Participants with organ failure
- •Participants with a chronic disease requiring immunologic or hormonal therapy
- •Participants with an allergy to immunotherapy and related cells
- •Participants with uncontrolled intercurrent illness
- •Participants with psychiatric illness/social situations that would limit compliance with study requirements
- •Participants with a history of organ transplantation or who are awaiting organ transplantation
研究组 & 干预措施
Low dose
Dose 1: 7x10^7 ABOUT γδT, local administration every 3-4 weeks
干预措施: Allogeneic γδ T (ABOUT) cells (Drug)
Medium dose
Dose 2: 1.1x10^8 ABOUT γδT, local administration every 3-4 weeks
干预措施: Allogeneic γδ T (ABOUT) cells (Drug)
High dose
Dose 3: 1.6x10^8 ABOUT γδT, local administration every 3-4 weeks
干预措施: Allogeneic γδ T (ABOUT) cells (Drug)
结局指标
主要结局
Incidence of Adverse Events (AEs)
时间窗: 3 months following ABOUT γδT cells administration
Defined as the incidence of ≥ Grade 3-4 adverse events related to ABOUT γδT cells according to common terminology criteria for adverse events (CTCAE) v6.0.
Incidence of Dose-Limiting Toxicities (DLTs)
时间窗: 28 days following initial treatment with ABOUT γδT cells
Defined as events attributable to ABOUT γδT cells infusion within 28 days post-infusion. Grade 3-4 acute graft-versus-host disease (GvHD) according to the Mount Sinai Acute GvHD International Consortium criteria; Grade 3 or higher cytokine release syndrome (CRS) lasting more than 2 weeks, according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria; Any ABOUT γδT cells-related AE requiring intubation; Grade 4 non-hematologic toxicities.
次要结局
- Objective Response Rate (ORR)(3 months following ABOUT γδT cells administration)
- Duration of response (DOR)(3 months following ABOUT γδT cells administration)
研究者
Chenlong YANG
Research Professor
Peking University Third Hospital