NCT05667155招募中1 期
Clinical Study of Cord Blood-derived CAR NK Cells Targeting CD19/CD70 in Refractory/Relapsed B-cell Non-Hodgkin Lymphoma
Second Affiliated Hospital, School of Medicine, Zhejiang University1 个研究点 分布在 1 个国家目标入组 48 人开始时间: 2022年12月15日最近更新:
适应症
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Incidence of dose limiting toxicity (DLTs)
研究概览
简要总结
To study the safety and efficacy of cord blood-derived CAR-NK cells targeting CD19/CD70 in patients with B-cell non-Hodgkin's lymphoma
详细描述
This is a single-center, open, one-arm, dose-escalation study to observe the safety and efficacy of cord blood-derived dualCAR-NK19/70 cells in patients with B-cell non-Hodgkin lymphoma.9-18 patients are planned to be enrolled in the dose-escalation trial (2×10^6 cells/kg, 4×10^6 cells/kg, 8×10^6 cells/kg) . Each dose was given once a week for 3 weeks.The primary endpoints are DLT, MTD, and the second endpionts are the overall response rates (CR and PR), overall survival, and progression-free survival. Based on the results in the dose-escalation trial, the recommended dose will be determined. Another 30 patients will be enrolled to estimate the safety and efficacy of CB CAR-NK019 under the best dose.
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
- •Voluntarily participate in the study and sign the informed consent;
- •Age 18-75, male and female;
- •Histologically confirmed diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (tFL), primary mediastinal B-cell lymphoma (PMBCL), mantle cell lymphoma (MCL), and other inert B-cell NHL transforming types:
- •(1)refractory or recurrent DLBCL and tFL must be approved by 2 line immune disease relapse after chemotherapy treatment; (2) refractory definition large B cell lymphoma (research SCHOLAR - 1 standard) : more than 4 courses first-line immune chemotherapy disease progression; The stable time of the disease is equal to or less than 6 months; Or disease progression or recurrence within 12 months after autologous hematopoietic stem cell transplantation; (3) refractory or recurrent MCL must be 1 line with immune chemotherapy; BTK inhibitors are resistant or intolerant as 2-line therapy; (4)always treatment must include CD20 single resistance (unless the subjects for CD20 negative) and anthracycline-based;
- •There was at least one measurable lesion with the longest diameter ≥1.5 cm;
- •Predicted survival ≥12 weeks;
- •The expression of CD19 or CD70 in biopsy sections of tumor tissue was positive;
- •ECOG score 0-2;
- •Adequate reserve of organ functions:
- •cereal third transaminase, aspartate aminotransferase 2.5 x or less UNL (upper limit of normal);
- •creatinine clearance (Cockcroft - Gault method) or 60 mL/min.
- •serum total bilirubin and alkaline phosphatase (1.5 x or less UNL.
- •glomerular filtration rate > 50 mL/min
- •heart ejection fraction (EF) 45% or higher;
- •indoor natural air environment, basic oxygen saturation > 92%
- •blood routine: neutrophils absolute number > 1000 cells/mm3, platelet count 45 x109, 8.0 g/dL hemoglobin;
- •Allowed to have received a previous stem cell transplant
- •Approved anti-B-cell lymphoma therapies, such as systemic chemotherapy, systemic radiotherapy and immunotherapy, had been completed for at least 3 weeks before the study. The eluting period of targeted drug regimens without chemotherapy was 2 weeks;
- •Patients who had previously received CAR T cell therapy and failed to respond to a 3-month evaluation or relapsed were admitted;
- •Female subjects of childbearing age must test negative for pregnancy and agree to use effective contraceptive methods during the trial
- •Two tests have come back negative for COVID-19.
排除标准
- •Allergic to any of the components of cell products;
- •History of other tumors;
- •Acute GvHD or generalized chronic GvHD with grade II-IV (Glucksberg standard) after previous allogeneic hematopoietic stem cell transplantation; Or being treated with anti-GVHD;
- •Had received gene therapy in the past 3 months;
- •Active infections requiring treatment (other than simple urinary tract infections and bacterial pharyngitis), however, prophylactic antibiotics, antiviral and antifungal infections are allowed;
- •Subjects 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 insufficiency according to the New York Heart Association Cardiac Function Grading criteria;
- •Patients who received antitumor therapy in the early stage but the toxicity reaction did not recover (CTCAE 5.0 toxicity reaction did not recover to ≤ level 1, except fatigue, anorexia and alopecia);
- •Subjects with a history of epilepsy or other central nervous system diseases;
- •Skull enhanced CT or MRI showing evidence of central nervous system lymphoma;
- •Lactating women who refuse to stop breastfeeding;
- •Any other circumstances that the investigator believes may increase the subject's risk or interfere with the test results.
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 B-cell Non-Hodgkin Lymphoma
次要结局
- Duration of response (DOR)(Up to 2 years)
- Overall survival (OS)(Up to 2 years)
- Overall response rate (ORR)(Up to 2 years)
- Progression free survival (PFS)(Up to 2 years)
- Complete response rate (CR)(Up to 2 years)
- Partial response rate (PR)(Up to 2 years)
研究者
研究点 (1)
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