Anti-PD-1 Antibody Armored γδ T Cells in the Treatment of Malignant Meningioma, a Phase I Clinical Trail
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 12
- 主要终点
- Safety evaluation: Incidence of Adverse events (AEs)
研究概览
简要总结
This study intends to combine the advantages of γδ T cells and PD-1 monoclonal antibody to conduct an exploratory clinical study on the safety and efficacy of PD-1 antibody armored γδ T cells (γδ T-PD-1 Ab cells) in the treatment of malignant meningioma.
详细描述
This is a single-center, single-arm, phase I clinical trial to evaluate the safety and efficacy of γδ T-PD-1 Ab cells in patients with malignant meningioma. A typical 3+3 dose-escalation design will be used to determine the optimal dose level of γδ T-PD-1 Ab cells based on the incidence of dose-limiting toxicity (DLT). The initial injection dose level will start from 1×10^7 to 1×10^8 in every 2 weeks.
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
- •The patient voluntarily signs the informed consent and can complete the follow-up examination, evaluation and treatment;
- •Age 18-70 years old (both ends included), both male and female;
- •The histopathological diagnosis was malignant solid tumor;
- •Tumor recurrence is confirmed by imaging (MRI) or re-biopsy/surgery;
- •ECOG score 0-2;
- •Expected survival ≥6 months;
- •Have received chemotherapy or targeted therapy more than 4 weeks ago;
- •Organ function requirements:
- •Bone marrow function: white blood cell count≥3×109, platelets ≥70×109/L, a hemoglobin (Hb) ≥90g/L; Liver function: total bilirubin ≤1.5 times the upper limit of normal (ULN); Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 times ULN; Renal function: serum creatinine level ≤1.5 ULN; Coagulation function: international normalized ratio (INR) does not exceed 1.5 times the upper limit of normal, and activated partial thromboplastin time (APTT) does not exceed 1.5 times the upper limit of normal.
- •Cardiac function: left ventricular ejection fraction (LVEF) > 55%
- •Pregnant women of childbearing age must have a negative serum pregnancy test within 28 days before treatment. Any fertile male and female patients must agree to use effective contraceptive methods throughout the study and for at least 12 weeks after the last study administration.
排除标准
- •Intolerance or allergy to any ingredient or similar drug in the treatment plan planned for this study;
- •Major organ dysfunction:
- •Cardiac function: Left ventricular ejection fraction (LVEF) ≤ 55%, New York Heart Association (NYHA) grade III or IV congestive heart failure, QTc > 480 msec, other cardiac diseases as determined by the investigator to be unsuitable for inclusion.
- •Liver function: Child-Pugh liver function classification C or above. Pulmonary function: Severe respiratory failure affecting other organs.
- •Uncontrolled epilepsy, severe bleeding risk (such as a recent history of cerebral hemorrhage).
- •Active and/or uncontrolled infections (such as tuberculosis, sepsis, opportunistic infections, active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection, human immunodeficiency virus (HIV) infection, Treponema pallidum (TP) infection).
- •Severe, uncontrolled systemic autoimmune or inflammatory diseases (such as systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, and temporal arteritis, Guillain-Barré syndrome (GBS), amyotrophic lateral sclerosis (ALS)).
- •Unstable systemic diseases: unstable angina pectoris, cerebrovascular accident or transient ischemia (within 6 months before screening), myocardial infarction (within 6 months before screening), grade III or IV cardiac dysfunction, refractory hypertension (refractory hypertension is defined as: after lifestyle improvement and using appropriate doses of ≥ 4 antihypertensive drugs (including diuretics), blood pressure cannot be effectively controlled after treatment for more than 1 month and still not controlled), severe arrhythmia requiring drug treatment, hepatic arrhythmia, liver disease, kidney disease or metabolic disorders.
- •Patients with other malignant tumors.
- •Major surgeries within 4 weeks before screening that were assessed by the investigator as unsuitable for inclusion.
- •Participated in other interventional clinical studies within 30 days before enrollment.
研究组 & 干预措施
γδ T-PD-1 Ab cells
o Cells will be extracted from a healthy donor, followed by ex-vivo expansion, activation and genetic engineering. The ex-vivo expanded γδ T-PD-1 Ab cells will be adoptively transfused to tumor patients.
干预措施: γδ T-PD-1 Ab cells (Biological)
结局指标
主要结局
Safety evaluation: Incidence of Adverse events (AEs)
时间窗: 96 weeks
Therapy-related adverse events will be recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0).
Safety evaluation: Dose limited toxicity (DLTs)
时间窗: 96 weeks
The incidence, characteristic and severity of DLTs will be recorded and assessed.
Safety evaluation: Maximum-tolerated dose (MTD)
时间窗: 96 weeks
MTD or clinical recommended dose will be recorded and evaluated.
次要结局
- Efficacy evaluation: Objective Response Rate(ORR)(12 weeks)
- Efficacy evaluation: Disease Control Rate (DCR)(12 weeks)
- Efficacy evaluation: Progress Free Survival(PFS)(12 weeks)
- Efficacy evaluation: Two-year Overall Survival Rate (OS)(96 weeks)
研究者
Fang Liu
MD
Nanjing Medical University