肿瘤细胞治疗研究
英文原题：Safety and Efficacy Study of Anti-PD1 Armored CD19 CAR-T Cells in Adult Subjects With Relapsed or Refractory Diffuse Large B-cell Lymphoma
这是一项 I 期注册临床试验，评估 CD19CAR-T 细胞治疗弥漫大 B 细胞淋巴瘤的安全性、可行性及初步疗效。当前状态：招募中。计划入组 30 例。试验地点：中国 · 苏州（共 1 个中心，其中中国 1 个）。登记号：NCT07368270。
不限性别 · ≥ 18 Years
纳入标准： 1. 自愿参加临床研究并签署知情同意书。 2. 年龄≥18岁，患复发/难治性弥漫大B细胞淋巴瘤，且符合以下任一情况：一线治疗6个周期后未达完全缓解，或3个周期后未达部分缓解；一线治疗后达到完全缓解但12个月内复发；全身治疗后达到完全缓解但随后复发/难治，且未计划移植，或拟行移植但二线治疗后仍不符合移植条件；或至少接受2个疗程二线治疗（包括自体造血干细胞移植）后仍未达完全缓解。 3. 预期生存期≥3个月。 4. 按2014 Lugano标准修订的恶性淋巴瘤疗效评价标准，至少有一个可测量病灶。 5. 流式细胞术或免疫组化检测证实肿瘤细胞表达CD19。 6. ECOG评分≤2。 7. 入组前器官功能充分：肾功能为血清肌酐≤ULN的1.5倍或估算肾小球滤过率（eGFR）≥60 mL/min/1.73 m²；肝功能为ALT≤年龄对应ULN的5倍、总胆红素≤2.0 mg/dL（Gilbert-Meulengracht综合征患者除外；此类患者总胆红素≤ULN的3倍且直接胆红素≤ULN的1.5倍时可入组）；肺储备功能为呼吸困难≤1级且室内空气下血氧饱和度>95%；血流动力学稳定，超声心动图或多门控核素显像（MUGA）测得LVEF≥45%。 8. 无需输血即可满足骨髓储备要求：ANC≥1×10⁹/L、淋巴细胞绝对计数（ALC）≥0.1×10⁹/L、血小板≥50×10⁹/L、血红蛋白>80 g/L。 9. 研究者判断受试者一般状况及生化指标正常或已得到充分代偿，能够接受淋巴细胞清除和CAR-T细胞治疗。 排除标准： 1. 妊娠或哺乳期，或计划在6个月内妊娠。 2. 感染性疾病（如HIV、活动性结核等）。 3. 活动性乙肝或丙肝感染。 4. 生命体征异常或拒绝接受检查。 5. 患有妨碍完成治疗或疗效评估的精神或心理障碍。 6. 有严重超敏反应史或已知对IL-2超敏。 7. 存在需要抗菌治疗的严重全身或局部感染。 8. 心、肺、脑、肾等重要器官功能显著受损，或研究者认为存在其他导致无法入组的情况。
Inclusion Criteria: * 1\. Subjects voluntarily participate in clinical research and sign informed consent. * 2\. Adult subjects (age ≥18 ) with relapsed or refractory diffuse large B-cell lymphoma: a) failure to achieve CR after 6 cycles, or PR after 3 cycles, of first-line therapy, or achieve CR after first-line therapy but relapse within 12 months; b) achieve CR after systemic treatment, but are refractory or relapsed, and no plan to transplant, or prepare for transplantation but cannot meet transplantation criteria after second-line therapy; c) not achieve CR after at least two courses of second-line treatment (including autologous stem cell transplantation). * 3\. Expected survival ≥ 3 months. * 4\. At least one measurable lesion as per revised IWG response criteria for malignant lymphom (2014 Lugano criteria). * 5\. CD19 positive expression are detected on tumor cells of subjects by flow cytometry or immunohistochemistry. * 6\. ECOG score ≤ 2. * 7\. Subjects with adequate organ functions prior to enrollment, meet the following laboratory values: * Renal function: serum creatinine ≤ 1.5 × ULN or estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m². * Hepatic function: Serum alanine aminotransferase (ALT) ≤ 5 × age-specific ULN and total bilirubin ≤ 2.0 mg/dL, except in subjects with Gilbert-Meulengracht syndrome. If total bilirubin ≤ 3.0 × ULN and direct bilirubin ≤ 1.5 × ULN, subjects with Gilbert-Meulengracht syndrome are included. * Pulmonary reserve: ≤ Grade 1 dyspnea and oxygen saturation \>95% on room air. * 8\. Stable hemodynamics and left ventricular ejection fraction (LVEF) ≥ 45 % assessed by echocardiography or multi-gated radionuclide angiography (MUGA). * 9\. Adequate bone-marrow reserve without blood transfusion as defined by: * Absolute neutrophil count (ANC) ≥ 1 x 10\^9/L. * Absolute lymphocyte count (ALC) ≥ 0.1 x 10\^9/L. * Platelets ≥ 50 x 10\^9/L. * Hemoglobin \>80g/L. * 10\. In the investigator's judgment, subjects' general condition and all biochemical values are either normal or sufficiently compensated to receive lymphodepletion and CAR-T cell therapy. Exclusion Criteria: * 1\. Women who are pregnant or breastfeeding, or planned pregnancy within 6 months. * 2\. Infectious disease(HIV, Active Tuberculosis ect.). * 3\. Active infection: hepatitis B, hepatitis C. * 4\. Abnormal vital signs or refuse to receive examination. * 5\. Subjects with psychiatric or psychological disorders are unable to complete treatment or efficacy assessment. * 6.History of severe hypersensitivity or known hypersensitivity to IL-2. * 7\. Systemic or local severe infection requiring antimicrobial therapy. * 8\. Significant dysfunction of vital organs (heart, lung, brain, kidney, etc.), or in the investigator's judgment, subjects are unable to be enrolled with any other condition.
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 (DLT) · Dose-limiting toxicity for each subject · 1 month after injection；AE/SAE · Incidence and severity of adverse events (AE), and serious adverse event (SAE) · 1 month, 3 months, 6 months, 12 months after injection
次要终点：Objective response rate (ORR)；Overall survival (OS)；Duration of response (DOR)；Progression-free survival (PFS)
受试者先接受氟达拉滨和环磷酰胺淋巴细胞清除治疗，随后输注抗PD-1装甲型CD19 CAR-T细胞。
本研究旨在研究抗PD-1装甲型CD19 CAR-T细胞治疗成人复发/难治性弥漫大B细胞淋巴瘤的安全性和耐受性。
The purpose of this study is to investigate the safety and tolerability of anti-PD1 armored CD19 CAR-T Cells in adult subjects with relapsed or refractory diffuse large B-cell lymphoma.
MEMBER ACCOUNT
登录成功会直接打开下一页。
