A Single-arm, Dose-escalation Phase I Clinical Study on Evaluating the Tolerability, Pharmacokinetic Characteristics, Safety and Preliminary Efficacy of MT027 in Patients with Recurrent or Progressive High-grade Glioma
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Dose Limiting Toxicity (DLT)
研究概览
简要总结
The clinical protocol plans to preset three dose groups, namely 1×10⁷ cells per dose, 3×10⁷ cells per dose, and 6×10⁷ cells per dose. The injection will be administered once every three weeks, adopting a "3 + 3" dose escalation design. The dosing interval is based on the pharmacokinetic (PK), safety and preliminary efficacy data of MT027 investigator-initiated trial (IIT) previously conducted at Dushu Lake Hospital of Soochow University. Accordingly, it is recommended to maintain the dosing interval of once every three weeks, with a window period of ±7 days. According to past experience, the dosing cycle should be at least 6 cycles, with each cycle lasting 21 days. If patients still benefit after more than 6 cycles, they can continue to receive the medication until no further benefit is achieved. The number of treatment sessions is approximately 6 to 9 times. However, the specific number of treatment sessions will generally be determined by the investigator based on the patient's disease condition.
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
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntarily participate in this study and sign the informed consent form.
- •Be aged between 18 and 70 years old (including the critical values), with no gender limitation.
- •Subjects with high-grade glioma diagnosed pathologically (referring to grade 3 or 4 in the "WHO (2021) Classification of Tumors of the Central Nervous System"), who have progressive disease during standard treatment or have recurrence after standard treatment.
- •Enhanced MRI shows space-occupying lesions in the brain, and there is at least one measurable lesion (according to the iRANO 2010 version criteria).
- •The tumor tissue of the patient has positive expression of B7-H
- •The subject voluntarily provides the most recent formalin-fixed paraffin-embedded (FFPE) tissue or pathological sections (at least 8 consecutive blank sections) for the detection of B7-H3 expression (immunohistochemistry, IHC).
- •Have an expected survival period of ≥ 3 months.
- •Have a Karnofsky Performance Scale (KPS) score of ≥ 70 points. -
排除标准
- •Patients with recurrence in the brainstem, spinal cord dissemination or extracranial metastasis;
- •The maximum diameter of a single tumor lesion is > 5 cm, or the cumulative maximum diameter of multiple lesions is > 6 cm;
- •Having received radiotherapy within 3 months before cell therapy or having received surgical treatment (except for Ommaya reservoir implantation), chemotherapy (except for lymphocyte depletion therapy), immunotherapy, molecular targeted therapy or any other anti-tumor therapy within 4 weeks before cell therapy;
- •Having participated in other drug clinical trials within 4 weeks before screening;
- •Having previously received CAR-T cell therapy;
- •Subjects with a severe allergy history to any component of the experimental drug or biological products;
- •Subjects with other primary malignancies (except for cured cervical carcinoma in situ and basal cell carcinoma of the skin);
- •Suffering from major diseases such as active systemic infection and coagulation disorders;
- •Suffering from severe insufficiency of heart, lung, liver and kidney functions; cardiac function: grade III or above according to the New York Heart Association (NYHA) criteria; liver function: grade C or above according to the Child-Pugh grading criteria; renal function: chronic kidney disease (CKD) stage 4 or above; renal insufficiency stage III or above; pulmonary function: severe respiratory failure symptoms involving other organs;
- •Subjects with severe autoimmune diseases;
- •Subjects who have previously received allogeneic tissue/solid organ transplantation;
- •Subjects who have received live vaccines within 2 weeks before the first cell therapy or who plan to receive live vaccines during the study period;
- •Subjects with active hepatitis B virus infection; or patients with hepatitis C virus infection (defined as positive HCV antibody, and those with HCV-RNA below the detection limit are allowed to enroll); or patients with human immunodeficiency virus infection (defined as positive HIV antibody); or patients with positive treponema pallidum antibody;
- •Having symptoms and signs of epilepsy or chronic intracranial hypertension that are difficult to control with drugs (for example, those using more than 500 ml of mannitol or more than 15 mg of dexamethasone or more than 80 mg of methylprednisolone or other hormones in equivalent doses per day);
- •Subjects judged by the investigator to have severe neurocognitive disorders;
- •Pregnant or lactating women;
- •Those who are considered by the investigator to be unsuitable for participating in this clinical study due to any clinical or laboratory examination abnormalities or other reasons.
研究组 & 干预措施
MT027
干预措施: MT027 cells suspension (Drug)
结局指标
主要结局
Dose Limiting Toxicity (DLT)
时间窗: 28 days
Adverse Events (AE) and Serious Adverse Events (SAE)
时间窗: through study completion, an average of 1 year
Immune effector cell-associated neurotoxicity syndrome (ICANs)
时间窗: through study completion, an average of 1 year
GvHD
时间窗: through study completion, an average of 1 year
CRS
时间窗: through study completion, an average of 1 year
次要结局
未报告次要终点