NK Cell Therapy for the Treatment of Malignant Solid Brain Tumors
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 27
- 试验地点
- 4
- 主要终点
- Incidence of Adverse Events (AEs)
研究概览
简要总结
This is a multi-center, open-label investigator-initiated trial (IIT) designed to evaluate the safety, tolerability, and feasibility of combined intracranial and intravenous administration of ex vivo expanded and activated natural killer (NK) cells in adult patients with malignant solid brain tumors who have failed standard treatment modalities. The primary objective is to determine the maximum tolerated dose (MTD) or maximum feasible dose (MFD) of the combined NK cell therapy. Secondary objectives include preliminary assessment of anti-tumor activity as measured by progression-free survival (PFS), overall survival (OS), objective response rate (ORR) per RANO criteria, and evaluation of the immunological effects of NK cell infusion in the tumor microenvironment and peripheral blood.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 malignant central nervous system tumor, with imaging suggestive of continued progression or recurrence after comprehensive treatment
- •Karnofsky Performance Status (KPS) ≥ 60%
- •Life expectancy > 4 weeks, and must be able to undergo an MRI with contrast
- •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)
- •Dexamethasone dose ≤ 4 mg/day or equivalent corticosteroid dose, or no dexamethasone administered
- •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 NK 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
Intracranial/Intrathecal Injection: 1x10^8 NK cells, every 2 weeks Intravenous Infusion: 2x10^8 NK cells, every 2 weeks
干预措施: Autologous NK cells (Drug)
Medium dose
Intracranial/Intrathecal Injection: 1x10^8 NK cells, every 2 weeks Intravenous Infusion: 9x10^8 NK cells, every 2 weeks
干预措施: Autologous NK cells (Drug)
High dose
Intracranial/Intrathecal Injection: 1x10^8 NK cells, every 2 weeks Intravenous Infusion: 2.9x10^9 NK cells, every 2 weeks
干预措施: Autologous NK cells (Drug)
结局指标
主要结局
Incidence of Adverse Events (AEs)
时间窗: 3 months following NK cells administration
Defined as the incidence of ≥ Grade 3-4 adverse events related to NK 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 NK cells
Defined as events attributable to NK cells infusion within 28 days post-infusion. 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 NK cells-related AE requiring intubation; Grade 4 non-hematologic toxicities.
次要结局
- Objective Response Rate (ORR)(3 months following NK cells administration)
- Duration of response (DOR)(3 months following NK cells administration)
研究者
Chenlong YANG
Professor
Peking University Third Hospital