Enhanced Histone H3.3-K27M Neoantigen Vaccine Therapy Against Diffuse Intrinsic Pontine Glioma (ENACTING)- A Phase I Clinical Trial
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Rate of the patients who survive for more than one year after surgery/biopsy in all the DIPG patients who receive H3.3-K27M neoantigen vaccine
研究概览
简要总结
Diffuse intrinsic pontine gliomas (DIPGs), which diffusely occupy the pons of brainstem, are the deadliest primary brain cancer in children. Biopsy for pathology plus radiotherapy remains the current standard-of-care treatment that is minimal effective. Thus, the median overall survival after diagnosis is just 10 months. Recent studies have identified a lysine 27-to-methionine (K27M) somatic mutation at histone H3 variant (H3.3), as a feature mutation in DIPGs. Several preclinical studies have already demonstrated H3.3-K27M as a promising target for immunotherapy. The researched vaccine is a cancer-treatment vaccine containing an H3.3-K27M targeted neoantigen peptide, that can be taken up by antigen-presenting cells (APCs). APCs can present the peptide with the major histocompatibility complex (MHC) molecules on cell surface, thereby activating neoantigen-specific T cells and triggering corresponding cytotoxic T cell immune responses to eliminate H3.3-K27M-expressing DIPG cells. The main goal of this study is investigating the safety and preliminary efficacy of the vaccine in treating newly-diagnosed DIPGs when the vaccine is administered in combination with the standard-of-care treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 5 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •A. First entry criteria
- •Age ≥ 5 years old;
- •Newly-diagnosed patients with DIPG appearance on MRI image;
- •HLA-A2 subtype;
- •The expected survival time exceeds 24 weeks;
- •The KPS score is greater than 50; B. Second entry criteria
- •The KPS score is greater than 50;
- •DIPG is diagnosed histologically on tumor tissue obtained by biopsy or surgical resection;
- •H3.3K27M mutation is detected on tumor tissue obtained by biopsy or surgical resection ;
- •Adequate organ functions that meet the following criteria: The absolute number of neutrophils: ≥1500/mm3 Platelet count: ≥75000/uL Hemoglobin: ≥80 g/L Creatinine≤1.5×ULN Bilirubin≤1.5×ULN ALT≤3×ULN AST≤3×ULN
- •Ability to comprehend and sign an informed consent form.
排除标准
- •With past medical history of malignant tumors (except being asymptomatic for more than 3 years);
- •History of allergy to chemotherapeutics or radiosensitizers for the treatment of cancer in central nervous system and head/neck;
- •History of allergy to the vaccine and its ingredients;
- •Comorbidity with HIV infection and/or acute phase of hepatitis B/C;
- •Any progressive diseases that hinder participation in the trial;
- •With unstable cardiovascular diseases such as coronary heart disease, angina pectoris, myocardial infarction, arrhythmia et.al.;
- •History of uncontrolled mental illnesses;
- •Inability to comprehend or sign informed consent form or abide by the research procedures;
- •Other conditions believed to hinder participation in this trial at investigator' discretion.
研究组 & 干预措施
Open surgical biopsy
A total of 15 subjects with open surgical biopsy indications will receive microsurgical resection, followed by conformal radiotherapy and administration of the researched vaccine.
干预措施: Histone H3.3-K27M Neoantigen Vaccine Therapy (Biological)
Stereotactic biopsy
A total of 15 subjects without open surgical biopsy indications will receive stereotactic biopsy, followed by conformal radiotherapy and administration of the researched vaccine.
干预措施: Histone H3.3-K27M Neoantigen Vaccine Therapy (Biological)
结局指标
主要结局
Rate of the patients who survive for more than one year after surgery/biopsy in all the DIPG patients who receive H3.3-K27M neoantigen vaccine
时间窗: One year after surgery or biopsy
One-year survival rate
Safety of histone H3.3-K27M neoantigen vaccine in treating newly diagnosed DIPGs
时间窗: All the Adverse events (AEs) were recorded until 24 weeks after the last shot
AEs were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
次要结局
- Rate of the patients who survive for more than two years after surgery/biopsy in all the DIPG patients who receive H3.3-K27M neoantigen vaccine(two years after surgery or biopsy)
- Median Progression-free survival time of the DIPG patients who receive H3.3-K27M neoantigen vaccine(start 4 weeks after the first shot and every 8 weeks until disease progression)
- Median Overall survival time of the DIPG patients who receive H3.3-K27M neoantigen vaccine(start 4 weeks after the first shot and every 8 weeks until death)
- Immunological effectiveness of H3.3-K27M neoantigen vaccine for the treatment of DIPG patients(baseline 1: pre-radiotherapy; baseline 2: immediately after completing radiotherapy; Day 15, Day 57, Day 85 and every 8 weeks thereafter until up to 2 years after the first shot.)
- Maximum Tolerated Dose of H3.3-K27M neoantigen vaccine to treat DIPGs(DLTs were monitored at timepoints of every vaccine shot until the 28th day after the first injection)
研究者
Yang Zhang
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No.119 South Fourth Ring West Road, Fengtai District, Beijing,100070 P.R.China
Beijing Tiantan Hospital