肿瘤细胞治疗研究
英文原题：Anti-CD33-CLL1 CAR-T Cells (ICG415) for the Treatment of Relapsed/Refractory Acute Myeloid Leukemia
这是一项 I 期注册临床试验，评估 CAR-T 细胞治疗急性髓系白血病的安全性、可行性及初步疗效。当前状态：招募中。计划入组 18 例。试验地点：中国 · 南昌（共 2 个中心，其中中国 2 个）。登记号：NCT07668557。
不限性别 · ≥ 18 Years 且 ≤ 70 Years
纳入标准： 1. 在任何筛选程序前，受试者或法定授权代表已签署经IRB/IEC批准的书面知情同意书。 2. 签署知情同意书时年龄≥18岁且≤70岁。 3. 根据2022 WHO分类确诊为急性髓系白血病（AML），符合《中国复发/难治性急性髓系白血病诊疗指南（2023年版）》中复发/难治性（R/R）AML的诊断标准：复发性AML：完全缓解（CR）后外周血重新出现白血病原始细胞、骨髓原始细胞≥5%，或髓外白血病浸润。难治性AML：两个疗程标准诱导化疗后未达到CR；CR后12个月内早期复发；晚期复发且对挽救化疗耐药；≥2次疾病复发或持续性髓外病变。 4. 流式细胞术检测骨髓白血病原始细胞CLL-1和CD33双阳性。 5. 若筛选时外周血可检测到原始细胞，流式细胞术检测肿瘤细胞表面免疫表型必须为CD4和CD8双阴性。 6. ECOG体能状态评分0-2。 7. 预期总生存期>3个月。 8. 有生育能力的女性：血清妊娠试验阴性，输注后1年内采取有效避孕措施。有生殖潜力的男性：输注后1年内采取有效屏障避孕措施，且输注后1年内不得捐献精子。 排除标准： 1. 在知情同意前曾接受过CAR-T细胞治疗或其他基因修饰细胞治疗。 2. 严重主要器官功能障碍：肾脏：eGFR<50 mL/min（Cockcroft-Gault公式）；肝脏：ALT/AST>3×ULN（若与疾病相关则>5×ULN），总胆红素>2×ULN（Gilbert综合征>3×ULN）；心脏：LVEF<50%，室内空气SpO₂<94%，未控制的严重心脏疾病。 3. 活动性未控制感染：HBsAg/HBV-DNA阳性，活动性HCV-RNA阳性，HIV阳性，梅毒抗体阳性，活动性未控制的EBV或CMV病毒血症。 4. 需要持续用药的不稳定性严重全身性疾病。 5. 筛选前30天内>2级出血或长期慢性抗凝治疗。 6. 未控制的危及生命的细菌、真菌或病毒感染。 7. 非白血病性中枢神经系统器质性疾病或活动性CNS-2/CNS-3白血病；既往接受过治疗且已缓解的中枢神经系统白血病允许入组。 8. 合并其他恶性肿瘤，但已治愈的原位癌或持续完全缓解≥5年的恶性肿瘤除外。 9. 筛选前30天内接种减毒活疫苗或计划在CAR-T输注后3个月内接种。 10. 在ICF签署前3个月内接受过任何其他研究性药物。 11. 筛选前6个月内接受过异基因造血干细胞移植。 12. 妊娠或哺乳期女性。 13. 有自杀倾向，持续酒精或违禁药物依赖。 14. 对研究产品、辅料或合并用药已知过敏。 15. 研究者判断的任何其他不适合参加试验的情况。
Inclusion Criteria: 1. Written informed consent approved by IRB/IEC obtained from subject or legally authorized representative prior to any screening procedures. 2. Age ≥ 18 years and ≤ 70 years at the time of informed consent signing. 3. Diagnosis of acute myeloid leukemia (AML) per 2022 WHO Classification, meeting criteria for relapsed/refractory (R/R) AML as defined in the Chinese Guidelines for the Diagnosis and Management of Relapsed/Refractory Acute Myeloid Leukemia (2023 Edition): Relapsed AML: Reappearance of leukemic blasts in peripheral blood, bone marrow blasts ≥5%, or extramedullary leukemic infiltration after complete remission (CR). Refractory AML: failure to achieve CR after two cycles of standard induction chemotherapy; early relapse within 12 months post-CR; late relapse with salvage chemotherapy resistance; ≥2 disease relapses or persistent extramedullary disease. 4. Bone marrow leukemic blasts positive for both CLL-1 and CD33 by flow cytometry. 5. If circulating blasts are detectable at screening, tumor cell surface immunophenotype must be CD4 and CD8 double-negative by flow cytometry. 6. ECOG performance status 0-2. 7. Expected overall survival \> 3 months. 8. Females of childbearing potential: negative serum pregnancy test and effective contraception for 1 year post-infusion. Males of reproductive potential: effective barrier contraception for 1 year post-infusion and no sperm donation within 1 year after infusion. Exclusion Criteria: 1. Prior receipt of CAR-T cell therapy or other genetically modified cell therapy prior to informed consent. 2. Severe major organ dysfunction: Renal: eGFR \< 50 mL/min (Cockcroft-Gault); Hepatic: ALT/AST \> 3 × ULN (\>5×ULN if disease-related), total bilirubin \> 2 × ULN (\>3×ULN for Gilbert syndrome); Cardiac: LVEF \< 50%, room air SpO₂ \<94%, uncontrolled severe cardiac disease. 3. Active uncontrolled infection: positive HBsAg/HBV-DNA, active HCV-RNA positivity, HIV positive, positive syphilis antibody, active uncontrolled EBV or CMV viremia. 4. Unstable severe systemic disease requiring continuous medication. 5. Grade \>2 bleeding within 30 days before screening or chronic long-term anticoagulant treatment. 6. Uncontrolled life-threatening bacterial, fungal or viral infection. 7. Non-leukemic central nervous system organic disease or active CNS-2/CNS-3 leukemia; previously treated and resolved CNS leukemia is permitted. 8. Concurrent other malignant tumor except cured in-situ carcinoma or malignancies with ≥5 years continuous complete remission. 9. Live-attenuated vaccines within 30 days before screening or planned within 3 months after CAR-T infusion. 10. Received any other investigational medicinal product within 3 months prior to ICF signature. 11. Allogeneic hematopoietic stem cell transplantation within 6 months before screening. 12. Pregnant or breastfeeding women. 13. Suicidal tendency, ongoing alcohol or illicit drug dependence. 14. Known hypersensitivity to investigational product, excipients or concomitant drugs. 15. Any other condition judged inappropriate for trial entry by investigator.
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 Toxicities (DLTs) · DLTs assessed according to the protocol-defined criteria. · Within 28 days after ICG415 CAR-T cell infusion；Incidence and Severity of Treatment-Emergent Adverse Events (TEAEs) · Frequency and severity of TEAEs graded by NCI-CTCAE Version 5.0, including changes from baseline in vital signs, physical examination, 12-lead ECG, and clinical laboratory parameters (complete blood count, urinalysis, blood chemistry, coagulation function, etc.). · From first dose through 24 months post infusion
次要终点：Objective Response Rate (ORR) at Months 1, 3, and 6；Rates of CR, CRi, and PR at Year 1 and Year 2；Cumulative Incidence of Relapse (CIR) at Year 1 and Year 2；Duration of Response (DOR)；Progression-Free Survival (PFS)；Overall Survival (OS)；Event-Free Survival (EFS)；CAR-T Cell Kinetics - Persistence over Time
这是一项单臂、开放标签的I期试验，旨在评估ICG415——一种靶向CD33和CLL1的自体CAR-T细胞——在复发或难治性急性髓系白血病（AML）患者中的安全性和耐受性。受试者接受淋巴细胞清除性化疗后，再进行自体CAR-T输注。主要目标是评估对标准AML治疗失败的患者的安全性和初步抗白血病疗效。
This single-arm, open-label phase I trial evaluates the safety and tolerability of ICG415, autologous CAR-T cells targeting CD33 and CLL1, in patients with relapsed or refractory acute myeloid leukemia (AML). Subjects receive lymphodepleting chemotherapy followed by autologous CAR-T infusion. The primary goal is to assess safety and preliminary anti-leukemic efficacy in patients failing standard AML therapies.
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