肿瘤细胞治疗研究
英文原题：Clinical Study of Cord Blood-derived CAR-NK Cells Targeting CD19 in the Treatment of Refractory/Relapsed B-cell NHL
⚠ 该试验的登记信息已有 19 个月未更新， 页面上显示的「招募中」可能已经失效。联系研究中心之前，建议先到 ClinicalTrials.gov 核对登记原文的最新状态与联系方式。
这是一项 I 期注册临床试验，评估抗 CD19CAR-NK 细胞治疗非霍奇金淋巴瘤的安全性、可行性及初步疗效。当前状态：招募中。计划入组 48 例。试验地点：中国 · 杭州（共 1 个中心，其中中国 1 个）。登记号：NCT05472558。
不限性别 · ≥ 18 Years 且 ≤ 75 Years
纳入标准： • 自愿参加研究并签署知情同意书；年龄18–75岁，性别不限。 • 组织学确诊弥漫大B细胞淋巴瘤（DLBCL）、转化型滤泡性淋巴瘤（TFL）、原发纵隔B细胞淋巴瘤（PMBCL）、套细胞淋巴瘤（MCL）或其他惰性B细胞淋巴瘤转化类型。复发/难治DLBCL包括：两线治疗后未达完全缓解；任一治疗期间疾病进展或疾病稳定期≤6个月；或自体造血干细胞移植后12个月内进展/复发。复发/难治MCL须对BTK抑制剂耐药或不耐受；惰性B细胞淋巴瘤须三线治疗失败或复发。既往治疗须包括抗CD20单克隆抗体（CD20阴性者除外）及蒽环类药物。 • 至少有1个最长径≥1.5 cm的可测量病灶；肿瘤穿刺组织CD19表达阳性。 • 预期生存期≥12周；ECOG体能状态0–2分。 • 器官功能储备充分：ALT/AST≤ULN的2.5倍；按Cockcroft-Gault公式计算的肌酐清除率≥60 mL/min；总胆红素及碱性磷酸酶≤ULN的1.5倍；肾小球滤过率>50 mL/min；心脏射血分数≥50%；室内空气下基础血氧>92%。允许既往造血干细胞移植。 • 系统化疗、系统放疗或免疫治疗等获批抗淋巴瘤治疗须在研究用药前至少3周结束。既往接受CAR-T且经评估3个月后失败或复发者可入组。 • 有生育能力女性妊娠试验阴性并同意采取有效避孕措施；新冠病毒检测两次阴性。 排除标准： • 对细胞产品任一成分过敏；有其他肿瘤史。 • 既往发生Glucksberg标准Ⅱ–Ⅳ级急性GVHD或广泛慢性GVHD，或正在接受抗GVHD治疗。 • 过去3个月内接受基因治疗。 • 存在需治疗的活动性感染（单纯尿路感染和细菌性咽炎除外）；允许预防性抗生素、抗病毒及抗真菌治疗。 • 乙肝（HBsAg阳性；HBV DNA<10³者不排除）、丙肝（包括病毒携带）、梅毒或其他获得性/先天性免疫缺陷（包括HIV）。 • NYHA心功能Ⅲ/Ⅳ级。 • 既往抗肿瘤治疗毒性尚未恢复至CTCAE 5.0版≤1级；疲劳、食欲减退及脱发除外。 • 有癫痫或其他中枢神经系统疾病史；头部增强CT/MRI提示中枢神经系统淋巴瘤。 • 既往接受其他CD19靶向药物。 • 哺乳期女性且不愿停止哺乳。 • 研究者认为可能增加受试者风险或干扰研究结果的其他情况。
Inclusion Criteria: * Inclusion Criteria: 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: 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 ； Refractory or relapsed MCL must be resistant to or intolerable to BTK inhibitors; Refractory or relapsed indolent B-cell NHL is the failure or recurrence of third-line treatment; 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; ECOG score 0-2 points; Sufficient organ function reserve: Alanine aminotransferase, aspartate aminotransferase ≤ 2.5× UNL (upper limit of normal value); Creatinine clearance rate (Cockcroft-Gault method) ≥60 mL/min; Serum total bilirubin and alkaline phosphatase ≤1.5× UNL; Glomerular filtration rate\>50Ml/min Cardiac ejection fraction (EF) ≥50%; 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. Exclusion Criteria: * 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; Have received 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 risk of the subject or interfere with the results of the test.
以上为辅助阅读译文。是否适合入组须由主治医生判断，最终以登记平台与研究者确认为准。
主要终点：Incidence of dose limiting toxicity (DLTs) · 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 · Up to 28 days
次要终点：Complete response rate (CR)；Progression free survival (PFS)；Duration of response (DOR)；Overall survival (OS)；Partial response rate (PR)；Overall response rate (ORR)；Immunogenicity after the infusion of CB CAR-NK019
所有受试者均接受CAR-NK019静脉给药。
本研究旨在评估脐带血来源CD19靶向CAR-NK细胞治疗B细胞非霍奇金淋巴瘤患者的安全性和疗效。
To study the safety and effectiveness of cord blood-derived CAR-NK cells targeting CD19 in patients with B-cell non-Hodgkin's lymphoma
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