An Exploratory Phase I Clinical Trial of a Universal mRNA Vaccine for Recurrent or Progressive High-grade Glioma
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: 1. 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. 2. 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.
• 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) ≥50. 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
⁃ Other:
• 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.