Clinical Study of Cord Blood-derived CAR-NK Cells Targeting CD19 in the Treatment of Refractory/Relapsed Central Nervous System Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- Enrolling By Invitation
- 发起方
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Incidence of dose limiting toxicity (DLTs)
研究概览
简要总结
This study is designed to evaluate the safety and efficacy of cord blood-derived CAR-NK019 in the treatment of refractory/relapsed central nervous system lymphoma.
详细描述
This study is a single-center, open, single-arm incremental, exploratory study designed to evaluate the safety and efficacy of cord blood-derived CAR-NK019 in the treatment of refractory/relapsed central nervous system lymphoma.
The study will be divided into two stages: Phase I is the dose escalation study, which is strictly based on the "3+3" dose escalation principle, and three dose groups are set up, which are administered through the ommaya capsule ventricle, and each dose is infused once a week for 3 weeks. Three to six subjects are intended to be enrolled in each dose group, with each subject observed for at least 28 days after receiving the initial infusion and a long-term follow-up period of two years after each infusion. Phase II is the dose expansion phase: The recommended dose and administration mode for this phase will be determined after comprehensive consideration based on safety data obtained in phase I, the proliferation and survival of CAR-NK cells in vivo, and clinical efficacy data, and 24 effective subjects will be recruited for further evaluation of efficacy and safety. Long-term follow-up lasted up to 2 years after the first CAR-NK transfusion in each patient.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with refractory/recurrent CNS lymphoma must meet all of the following criteria to be eligible:
- •Voluntarily participate in the study and sign the informed consent;
- •Age 18-75 years old, male or female;
- •Diffuse large B-cell lymphoma (DLBCL) was confirmed by histology. CD19 expression was positive by lymphoma pathology or flow cytometry, and CD19 expression was ≥20% by IHC.
- •Imaging showed no evidence of systemic lymphoma;
- •Meets any of the following definitions for refractory/relapsed CNS lymphoma: no complete response has been achieved with prior 2-line regimen including methotrexate or cytarabine-based regimen; Disease progression during any treatment; The stable time of disease after effective treatment is less than 6 months; Disease progression or recurrence within 12 months after autologous hematopoietic stem cell transplantation.
- •Imaging showed the presence of at least one measurable lesion, with a minimum diameter of ≥10mm;
- •Expected survival ≥3 months;
- •ECOG score 0-3 points;
- •Adequate organ function reserve:
- •alanine aminotransferase, ASpartate aminotransferase ≤ 2.5× UNL (upper limit of normal);
- •Creatinine clearance (Cockcroft-Gault method) ≥60 mL/min;
- •Serum total bilirubin and alkaline phosphatase ≤1.5× UNL;
- •Glomerular filtration rate >50ml/min
- •cardiac ejection fraction (EF) ≥45%;
- •Basic oxygen saturation >92% in indoor natural air environment;
- •Blood routine: absolute number of neutrophils >×109/L, platelet count 45×109/L, hemoglobin 80g/L;
- •Previous autologous hematopoietic stem cell transplantation is allowed, and the interval between stem cell transfusion and CAR-NK transfusion is ≥3 months;
- •Previous CAR-T cell therapy is allowed, and the time interval between CAR-T transfusion and CAR-NK transfusion is ≥3 months;
- •Female subjects of childbearing age must test negative for pregnancy and agree to use effective contraception during the test;
- •Approved anti-tumor therapies, such as systemic chemotherapy, whole body radiotherapy and immunotherapy, have been discontinued for at least 3 weeks before the study; Discontinuation of targeted drug regiments without chemotherapy for at least 2 weeks;
排除标准
- •Subjects who meet any of the following criteria will not be admitted to the study:
- •Allergic to any of the components of cell products;
- •History of other tumors;
- •Acute grade II-IV (Glucksberg standard) GvHD or generalized chronic GvHD occurred after previous allogeneic hematopoietic stem cell transplantation; Or are receiving anti-GVHD treatment;
- •Have received gene therapy within the past 3 months;
- •Active infections requiring treatment (except simple urinary tract infections, bacterial pharyngitis), but prophylactic antibiotic, antiviral and antifungal infection treatment is permitted;
- •Persons infected with hepatitis B (HBsAg positive, but HBV-DNA<103 is not excluded) or hepatitis C virus (including virus carriers), syphilis and other acquired and congenital immunodeficiency diseases, including but not limited to HIV-infected persons;
- •Subjects with Grade III or IV cardiac dysfunction according to the New York Heart Association's cardiac function grading criteria;
- •Patients who received antitumor therapy in the early stage but did not recover toxicity (CTCAE 5.0 toxicity did not recover to ≤ grade 1, except fatigue, anorexia, alopecia);
- •Previous history of epilepsy, autoimmune encephalitis, cerebral infarction or cerebral hemorrhage within 6 months;
- •Whole-body enhanced CT or PET/CT suggests evidence of systemic lymphoma;
- •Lactating women who are unwilling to stop breastfeeding;
- •Any other circumstances that the investigator believes may increase the risk to the subject or interfere with the test results;
- •Patients requiring more than 10mg of dexamethasone per day for 3 days prior to enrollment;
- •Patients who cannot tolerate ommaya capsule implantation;
- •Those who cannot tolerate enhanced magnetic resonance imaging.
研究组 & 干预措施
CB CAR-NK019
干预措施: anti-CD19 CAR-NK cells (Biological)
结局指标
主要结局
Incidence of dose limiting toxicity (DLTs)
时间窗: Up to 28 days
To evaluate the safety, tolerability, and determine the recommended dosage of cord blood-derived Anti-CD19 CAR-NK Cell Therapy for refractory/relapsed central nervous system lymphoma
次要结局
- Overall response rate (ORR)(3 months)
- Complete response rate (CR)(3 months)
- Duration of response (DOR)(Up to 2 years)
- Progression free survival (PFS)(Up to 2 years)
- Overall survival (OS)(Up to 2 years)