H3K27M-specific Engineered Immune Effectors (EIE) Targeting Diffuse Midline Glioma/Diffuse Intrinsic Pontine Glioma
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Percentage of adverse effects after H3K27M-EIE injection
研究概览
简要总结
The purpose of this study is to assess the feasibility, safety and efficacy of H3K27M-specific engineered immune effector (EIE) therapy in patients with high-risk, H3K27M-positive diffuse midline glioma/diffuse intrinsic pontine glioma. Another goal of the study is to learn more about the function of the anti-H3K27M EIE cells and their persistency in patients.
详细描述
Important Regulatory Notice:
This trial record is only for global academic information registration on ClinicalTrials.gov. Neither the sponsor Beijing Meikang Jimian Biotechnology Co., Ltd. nor collaborator Shenzhen Geno-Immune Medical Institute has obtained NMPA clinical trial approval or clinical technology filing permission to carry out interventional cell therapy trials in mainland China.
ClinicalTrials.gov registration alone does not represent legal approval by Chinese health and drug regulatory authorities.
Diffuse midline glioma or Diffuse Intrinsic Pontine Glioma (DIPG) represent one of the most devastating pediatric central nervous system malignancies. Despite decades of clinical investigation, the standard of care remains focal radiotherapy, which offers only transient symptomatic improvement without altering the uniformly fatal disease trajectory. The median overall survival remains approximately 11 months from diagnosis, with five-year overall survival below 1%. No effective salvage therapies exist following disease progression, and conventional cytotoxic chemotherapy has failed to improve outcomes. The identification of the clonal H3K27M mutation in histone H3 as a driver of tumorigenesis has provided a unique tumor-specific antigenic target, distinguishing this entity from adult high-grade gliomas and opening avenues for innovative precision immunotherapy.
The H3K27M mutation serves as an ideal immunotherapeutic target due to its uniform expression across tumor cells, its absence in normal healthy tissues, and its critical role in oncogenesis. This study incorporates the production and adoptive transfer of autologous H3K27M-specific EIEs. Peripheral blood mononuclear cells (PBMCs) are collected via leukapheresis and stimulated with H3K27M antigen primed autologous dendritic cells. The resultant EIEs phenotypically characterized for CD8+, CD4+ and CD56+ predominance with antigen specificity. Here, the study aims to evaluate the safety and efficacy of the H3K27M-specific EIEs in DMG/DIPG patients.
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
- 2 Years 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Abilities to understand and the willingness to provide written informed consent;
- •≥ 2 and ≤ 70 years old;
- •Recurrent or refractory diffuse midline glioma or diffuse intrinsic pontine glioma patients with confirmed H3K27M mutation and documented lesions. Patients have received standard care of medication, such as gross total resection with concurrent radio-chemotherapy (~54 - 60 Gy, TMZ). Patients must either not be receiving dexamethasone or receiving ≤ 4 mg/day at the time of leukopheresis;
- •Karnofsky performance score (KPS) ≥ 60;
- •Life expectancy >3 months;
- •Satisfactory bone marrow, liver and kidney functions as defined by the following: absolute neutrophile count ≥ 1500/mm^3; hemoglobin > 10 g/dL; platelets > 100000 /mm^3; Bilirubin < 1.5×ULN; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 2.5×ULN; creatinine < 1.5×ULN;
- •Peripheral blood absolute lymphocyte count must be above 0.8×10^9/L;
- •Satisfactory heart functions;
- •Must be willing to follow the instructions of doctors; Women of reproductive potential (between 15 and 49 years old) must have a negative pregnancy test within 7 days of study start. Male and female patients of reproductive potential must agree to use birth control during the study and 3 months post study.
排除标准
- •A prior history of gliadel implantation 4 weeks before this study start or currently receiving antibody based therapies;
- •HIV positive;
- •Tuberculosis infection not under control;
- •History of autoimmune disease, or other diseases require long-term administration of steroids or immunosuppressive therapies;
- •History of allergic disease, or allergy to immune cells or study product;
- •Patients already actively enrolled in other immune cell clinical study; Patients, in the opinion of investigators, may not be eligible or not able to comply with the study.
结局指标
主要结局
Percentage of adverse effects after H3K27M-EIE injection
时间窗: up to one month
To assess the safety of autologous H3K27M-EIEs in vivo. The percentage of patients who have adverse effects will be evaluated by using the NCI CTCAE V4.0 criteria.
次要结局
- Rate of successful H3K27M-EIE generation(up to one month)
- Ability of H3K27M-EIE cells to induce cancer-specific reactions(after 1 month from H3K27M-EIE cell infusion until 12 months after infusion)
- Ability of H3K27M-EIE cells inducing anti-cancer reactions(after 1 month from H3K27M-EIE cell infusion until 24 months after infusion)