An Exploratory Phase I Clinical Trial of a Universal mRNA Vaccine for Recurrent or Progressive High-grade Glioma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Safety and tolerability of a mRNA vaccine
研究概览
简要总结
This clinical trial is designed to evaluate the safety and efficacy of a universal mRNA vaccine targeting a panel of glioma-associated mutations in patients with recurrent or progressive high-grade glioma.
The primary objectives are to address the following key questions: 1) Is the mRNA vaccine safe for this patient population? 2) Does the vaccine stimulate an anti-tumor immune response and promote tumor regression?
Participants will receive the vaccine according to the following schedule:
- one injection per week for four consecutive weeks, followed by one injection every four weeks for four cycles, and subsequently, one injection every 12 weeks for maintenance.
- Safety and efficacy assessments, including detailed recording of adverse events and tumor growth evaluation, will be conducted at follow-up visits scheduled for weeks 6, 12, and months 6, 9, 12, 18, 24, and 36 post-treatment initiation.
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
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adequate compliance, ability to comprehend the clinical trial, and provision of written informed consent.
- •Male or female, aged ≥16 years.
- •Histologically or cytologically confirmed WHO Grade III or IV glioma harboring one or more of the following mutations: H3.3K27M, H3.1K27M, H3.3G34R, BRAF V600E, PIK3CA H1047R, IDH1 R132H, or EGFRvIII.
- •Recurrent or progressive high-grade glioma, defined as a CNS WHO Grade 3-4 glioma confirmed by post-surgical histopathology, with documented recurrence or progression per RANO criteria on MRI following standard therapy (radiotherapy plus temozolomide chemotherapy).
- •Life expectancy ≥3 months.
- •Karnofsky Performance Status (KPS) ≥
- •For subjects with spinal cord lesions, functional deficits due to paralysis will not be considered in the KPS assessment.
- •Absence of significant bone marrow, cardiac, pulmonary, or renal dysfunction, defined as:
- •Hematologic (without transfusion or hematopoietic growth factor support within 14 days):
- •Absolute Neutrophil Count (ANC) ≥1.5 × 10⁹/L
- •Platelet count (PLT) ≥100 × 10⁹/L
- •Hemoglobin (HGB) ≥90 g/L
- •Hepatic Function:
- •Alanine Aminotransferase (ALT) ≤2.5 × Upper Limit of Normal (ULN)
- •Aspartate Aminotransferase (AST) ≤2.5 × ULN
- •Total Bilirubin (TBIL) ≤1.5 × ULN
- •Renal Function:
- •* Serum creatinine ≤1.5 × ULN OR estimated creatinine clearance ≥50 mL/min (calculated using the Cockcroft-Gault formula)
- •Coagulation:
- •Activated Partial Thromboplastin Time (APTT) ≤1.5 × ULN
- •International Normalized Ratio (INR) ≤1.5 × ULN
- •Left Ventricular Ejection Fraction (LVEF) ≥50% without clinically significant pericardial effusion on echocardiogram
- •No clinically significant electrocardiogram (ECG) abnormalities
- •Baseline oxygen saturation >92% on room air
- •Adequate immune function, defined as receiving dexamethasone ≤2 mg/day within the 3 days prior to screening without severe lymphopenia.
- •Negative pregnancy test for women of childbearing potential (WOCBP); non-pregnant and non-lactating females; both male and female participants must agree to use highly effective contraception and have no plan for pregnancy within 6 months after study entry.
排除标准
- •History of other malignancies within the past 5 years (except appropriately treated carcinoma in situ of the cervix or non-melanoma skin cancer).
- •History of hypersensitivity to chemotherapy agents or radiosensitizers used for central nervous system or head and neck cancers.
- •History of severe allergic reactions to vaccines or any components of the investigational product.
- •Positive serology for:
- •Human Immunodeficiency Virus (HIV) antibody
- •Hepatitis C Virus (HCV) antibody with detectable HCV RNA
- •Hepatitis B Surface Antigen (HBsAg) with HBV DNA ≥2000 IU/mL
- •Treponema pallidum (TP) antibody with a positive confirmatory test (e.g., RPR/TPPA)
- •Active, uncontrolled infection, active tuberculosis, or active immunosuppressive disease.
- •Any concurrent non-malignant illness or psychiatric condition that would preclude safe protocol participation; uncontrolled cardiovascular disease (e.g., coronary artery disease, angina, myocardial infarction, significant arrhythmias).
- •Inability or unwillingness to provide informed consent or participate voluntarily.
- •Concurrent participation in another interventional clinical trial or participation within 3 months prior to screening.
- •Severe infection or signs/symptoms of active infection within 2 weeks prior to the first dose of the investigational product.
- •Administration of a live-attenuated vaccine within 4 weeks prior to the first dose.
- •History of solid organ or hematopoietic stem cell transplantation.
- •Any other condition that, in the opinion of the investigator, would jeopardize the subject's safety or compliance with the study protocol.
研究组 & 干预措施
mRNA vaccine treatment group
Participants in this arm receive the glioma-related multi-trageted mRNA vaccine.
干预措施: Glioma-related multi-target mRNA vaccines (Biological)
结局指标
主要结局
Safety and tolerability of a mRNA vaccine
时间窗: 2-3 years
All adverse events (AEs) treatment, emergent adverse events, treatment related toxici will be recorded. AE severity will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version \[Specify Version, e.g., 5.0\]. Dose-limiting toxicities (DLTs) are defined as occurring within the DLT observation period \[Specify period, e.g., 28 days after the first dose\] and include: 1. Any CTCAE Grade 4 local injection site reaction. 2. Any CTCAE Grade 3 local injection site reaction persisting for ≥2 weeks despite optimal supportive care. 3. Any hypersensitivity reaction of at least CTCAE Grade 3 severity. 4. CTCAE Grade 4 cerebral edema. 5. Autoimmune reactions of CTCAE Grade 3 or higher. 6. Any CTCAE Grade 4 hematologic toxicity (e.g., neutropenia, thrombocytopenia, anemia). 7. CTCAE Grade 3 or higher non-hematologic organ toxicity, with the following
次要结局
- Immune response to mRNA vaccine(1-5 years)