NCT06707259招募中1 期
Clinical Study of Cord Blood-derived IL-10/IL-15 CD19-CAR NK in the Treatment of Refractory/Relapsed B-cell NHL
Second Affiliated Hospital, School of Medicine, Zhejiang University1 个研究点 分布在 1 个国家目标入组 24 人开始时间: 2024年12月1日最近更新:
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 24
- 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 effectiveness of cord blood-derived IL-10/IL-15 CD19-CAR NK in patients with B-cell non-Hodgkin's lymphoma
详细描述
This is an open, single-arm, single-dose, dose-escalation clinical trial designed to evaluate the safety and the preliminary efficacy of CB IL-10/IL-15 CD19-CAR NK cells. 6-24 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). Based on the results in the dose-escalation trial, the recommended dose will be determined. Another 30 patients will be enrolled in the dose-expansion trial. The primary endpoints are DLT and MTD; the second is the overall response rates (CR and PR), survival, and progression-free survival. Patients will be infused on day 0, day 3, and day 6， respectively.
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
- •Volunteer to participate in this study and sign an informed consent form;
- •Age 18-75 years old, no gender limit;
- •Histologically diagnosed as diffuse large B-cell lymphoma (DLBCL), transforming follicular lymphoma (TFL), primary mediastinal B-cell lymphoma (PMBCL), mantle cell lymphoma (MCL) and other inert B-cells NHL conversion type:(1) Refractory or relapsed DLBCL refers to the failure to achieve complete remission after 2-line treatment; disease progression during any treatment, or disease stable time equal to or less than 6 months; or disease progression or recurrence within 12 months after autologous hematopoietic stem cell transplantation ； (2) Refractory or relapsed MCL must be resistant to or intolerable to BTK inhibitors; (3) Refractory or relapsed indolent B-cell NHL is the failure or recurrence of third-line treatment; (4) Previous treatment must include CD20 monoclonal antibody treatment (unless the subject is CD20 negative) and anthracyclines;
- •At least one measurable lesion with the longest diameter ≥ 1.5 cm exists;
- •The expected survival period is ≥12 weeks;
- •The puncture section of the tumor tissue was positive for CD19 expression; 7, ECOG score 0-2 points;
- •Sufficient organ function reserve: (1) Alanine aminotransferase, aspartate aminotransferase ≤ 2.5× UNL (upper limit of normal value); (2) Creatinine clearance rate (Cockcroft-Gault method) ≥60 mL/min; (3) Serum total bilirubin and alkaline phosphatase ≤1.5× UNL; （4）Glomerular filtration rate>50Ml/min Cardiac ejection fraction (EF) ≥50%; (5) Under natural indoor air environment, basic oxygen saturation>92% .
- •Allow a previous stem cell transplantation.
- •The approved anti-B-cell lymphoma treatments, such as systemic chemotherapy, systemic radiotherapy, and immunotherapy, have been completed for at least 3 weeks before the study medication;
- •Allow patients who have previously received CAR-T cell therapy and have failed or relapsed after 3 months of evaluation;
- •Female subjects of childbearing age must have a negative pregnancy test and agree to take effective contraceptive measures during the trial.
- •Two tests for the new coronavirus were negative.
排除标准
- •Those who have a history of allergies to any of the ingredients in cell products;
- •History of other tumors;
- •Previously presented with II-IV degree (Glucksberg criteria) acute GvHD or extensive chronic GvHD; or are receiving anti-GvHD treatment;
- •Have received gene therapy in the past 3 months;
- •Active infections that require treatment (except for simple urinary tract infections and bacterial pharyngitis), but preventive antibiotics, antiviral and antifungal infection treatments are allowed;
- •Hepatitis B (HBsAg positive, but HBV-DNA <103 is not an exclusion criterion) or hepatitis C virus infection (including virus carriers), syphilis and other subjects with acquired and congenital immunodeficiency diseases, including but not limited to people living with HIV;
- •According to the New York Heart Association's Heart Function Classification Standard, it is classified as Grade III or Grade IV impaired subjects;
- •Those who have received anti-tumor therapy in the early stage but the toxic reaction has not recovered (the CTCAE 5.0 toxic reaction has not recovered to ≤1, except for fatigue, anorexia, and hair loss);
- •Subjects with a history of epilepsy or other central nervous system diseases;
- •Enhanced CT or MRI of the head showed evidence of central nervous system lymphoma;
- •11. Have any other drugs that target CD19;
- •Women who are breastfeeding and unwilling to stop breastfeeding;
- •Any other situation that the investigator believes may increase the subject's risk or interfere with the test results.
研究组 & 干预措施
CB IL-10/IL-15-CD19-CAR NK
Experimental
All subjects were intravenously administrated with IL-10/IL-15 CD19-CAR NK
干预措施: anti-CD19 IL10/IL15 CAR-NK (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, and tolerability, and determine the recommended dosage of cord blood-derived Anti-CD19 IL10/IL15-CAR-NK Cell Therapy for B-cell Non-Hodgkin Lymphoma
次要结局
- Complete response rate (CR)(Up to 2 years)
- Progression free survival (PFS)(Up to 2 years)
- Duration of response (DOR)(Up to 2 years)
- Overall survival (OS)(Up to 2 years)
- Partial response rate (PR)(Up to 2 years)
- Overall response rate (ORR)(Up to 2 years)
研究者
研究点 (1)
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