肿瘤细胞治疗研究
英文原题：Exploratory Clinical Study on the Safety and Efficacy of CAR-T Cell Therapy in the Treatment of Relapsed/Refractory Myeloid Malignancies
⚠ 该试验的登记信息已有 18 个月未更新， 页面上显示的「尚未开始招募」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/II 期注册临床试验，评估 CAR-T 细胞治疗髓系恶性肿瘤的安全性、可行性及初步疗效。当前状态：尚未开始招募。计划入组 45 例。试验地点：中国 · 武汉（共 1 个中心，其中中国 1 个）。登记号：NCT06917105。
不限性别 · ≥ 18 Years
纳入标准： * 知情同意：愿意且能够提供书面知情同意，并承诺遵守计划访视、研究治疗、实验室检查及其他试验程序。 年龄：≥18岁，性别不限。 诊断：经病理学确诊的髓系恶性肿瘤（包括但不限于AML或MDS），符合复发/难治标准： 复发性疾病：达到CR/CRi后，接受≥2线挽救治疗后外周血中白血病细胞重新出现、骨髓原始细胞>5%或髓外复发。 难治性疾病：接受≥2个周期标准强化化疗后未能达到CR/CRi。 抗原表达：经免疫组织化学（IHC）或流式细胞术确认肿瘤细胞CD33、CD123和/或CLL-1阳性。 预期生存期：自签署知情同意书之日起≥3个月。血液学标准：血红蛋白≥70 g/L（允许输血）。 器官功能： 肾脏：血清肌酐≤1.5×ULN。心脏：左心室射血分数（LVEF）≥50%。肺：室内空气中氧饱和度>90%。肝脏：总胆红素≤1.5×ULN；ALT/AST≤2.5×ULN。体能状态：美国东部肿瘤协作组（ECOG）体能状态评分0-2。 排除标准： * 心脏功能障碍：重度心功能不全伴左心室射血分数（LVEF）<50%。 肺部疾病：重度肺功能障碍病史（如需要氧疗的慢性呼吸衰竭、间质性肺病或肺动脉高压）。 合并恶性肿瘤：除髓系肿瘤外的活动性/进展性恶性肿瘤（例外：充分治疗的非黑色素瘤皮肤癌或原位癌）。 未控制感染：需要全身抗微生物治疗（抗菌、抗病毒或抗真菌）且临床未缓解的活动性严重感染。 免疫疾病： 6个月内需要免疫抑制治疗的严重自身免疫性疾病。原发性免疫缺陷病（如普通变异型免疫缺陷病、严重联合免疫缺陷病）。 病毒感染： 活动性乙型肝炎（HBV-DNA≥2000 IU/mL）或丙型肝炎（HCV-RNA阳性）。HIV感染、AIDS或未经治疗的梅毒（经血清学检测确认）。超敏反应：对生物制品（包括抗生素）有严重过敏反应（≥3级）史。 移植并发症：异基因造血干细胞移植受者伴有： 3个月内急性移植物抗宿主病（GvHD）≥II级。4周内因GvHD正在接受免疫抑制治疗。 一般排除： 任何可能具有以下情况的躯体、精神或实验室异常： 显著增加研究风险（如未控制的糖尿病、NYHA III/IV级心力衰竭）。 影响方案依从性或数据解读。研究者判定不适合参加试验。
Inclusion Criteria: * Informed Consent: Willing and able to provide written informed consent, with commitment to comply with scheduled visits, study treatment, laboratory tests, and other trial procedures. Age: ≥18 years, regardless of gender. Diagnosis: Pathologically confirmed myeloid malignancy (including but not limited to AML or MDS) meeting relapsed/refractory criteria: Relapsed Disease: Reappearance of leukemic cells in peripheral blood, bone marrow blasts \>5%, or extramedullary relapse after achieving CR/CRi with ≥2 lines of salvage therapy. Refractory Disease: Failure to achieve CR/CRi after ≥2 cycles of standard intensive chemotherapy. Antigen Expression: Tumor cell positivity for CD33, CD123, and/or CLL-1 confirmed by immunohistochemistry (IHC) or flow cytometry. Life Expectancy: ≥3 months from the date of informed consent signing. Hematologic Criteria: Hemoglobin ≥70 g/L (transfusion permitted). Organ Function: Renal: Serum creatinine ≤1.5×ULN. Cardiac: Left ventricular ejection fraction (LVEF) ≥50%. Pulmonary: Oxygen saturation \>90% on room air. Hepatic: Total bilirubin ≤1.5×ULN; ALT/AST ≤2.5×ULN. Performance Status: Eastern Cooperative Oncology Group (ECOG) performance status score 0-2. Exclusion Criteria: * Cardiac Dysfunction: Severe cardiac insufficiency with left ventricular ejection fraction (LVEF) \<50%. Pulmonary Disease: History of severe pulmonary dysfunction (e.g., chronic respiratory failure, interstitial lung disease, or pulmonary hypertension requiring oxygen therapy). Concurrent Malignancy: Active/progressive malignancy other than myeloid neoplasms (exceptions: adequately treated non-melanoma skin cancer or carcinoma in situ). Uncontrolled Infection: Active severe infection requiring systemic antimicrobial therapy (antibacterial, antiviral, or antifungal) without clinical resolution. Immune Disorders: Severe autoimmune disease requiring immunosuppressive therapy within 6 months. Primary immunodeficiency disorders (e.g., common variable immunodeficiency, severe combined immunodeficiency). Viral Infections: Active hepatitis B (HBV-DNA ≥2000 IU/mL) or hepatitis C (HCV-RNA positive). HIV infection, AIDS, or untreated syphilis (confirmed by serological testing). Hypersensitivity: History of severe allergic reaction (Grade ≥3) to biological products, including antibiotics. Transplant Complications: Allogeneic hematopoietic stem cell transplant recipients with: Acute graft-versus-host disease (GvHD) ≥ Grade II within 3 months. Ongoing immunosuppressive therapy for GvHD within 4 weeks. General Exclusion: Any physical, psychiatric, or laboratory abnormality that may: Significantly increase study risk (e.g., uncontrolled diabetes, NYHA Class III/IV heart failure). Compromise protocol compliance or data interpretation. Investigator-determined unsuitability for trial participation.
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：The incidence of adverse events · Day 28
次要终点：Objective response rate (ORR)；Complete response rate (CRR)；Duration of response (DOR)；Progression free survival (PFS)；Overall survival (OS)
这是一项开放标签、单臂、探索性临床试验，采用“3+3”剂量递增后接剂量扩展，评估CD33/CD123/CLL-1 CAR-T细胞疗法在复发/难治性髓系恶性肿瘤患者中的安全性、最大耐受剂量（MTD）、药代动力学（PK）及初步疗效。 A部分：剂量递增阶段。遵循“3+3”剂量递增设计，设四个预设剂量队列：0.2×10⁶、0.5×10⁶、1×10⁶和2×10⁶ CAR阳性细胞/kg。预计入组：12-24例受试者。主要目的：评估安全性和耐受性，确定MTD。剂量限制性毒性（DLT）观察期：输注后28天。 B部分：剂量扩展阶段。入组21例额外受试者，接受在A部分确定的推荐II期剂量（RP2D）的CAR-T细胞输注。主要目的：进一步评估治疗疗效。 总体研究目标：CD33/CD123/CLL-1 CAR-T疗法的安全性特征。疗效终点（如缓解率、生存结局）。CAR-T细胞的药代动力学特征（扩增/持久性）。
This is an open-label, single-arm, exploratory clinical trial utilizing a "3+3" dose escalation followed by dose expansion to evaluate the safety, maximum tolerated dose (MTD), pharmacokinetics (PK), and preliminary efficacy of CD33/CD123/CLL-1 CAR-T cell therapy in patients with relapsed/refractory myeloid malignancies. Part A: Dose Escalation Phase. Follows a "3+3" dose escalation design with four predefined dose cohorts: 0.2×10⁶, 0.5×10⁶, 1×10⁶, and 2×10⁶ CAR-positive cells/kg.Anticipated enrollment: 12-24 subjects.Primary objectives: Assess safety, tolerability, and determine MTD.Dose-limiting toxicity (DLT) observation period: 28 days post-infusion. Part B: Dose Expansion Phase.Enrolls 21 additional subjects to receive CAR-T cell infusion at the recommended Phase 2 dose (RP2D) established in Part A.Primary objective: Further evaluate therapeutic efficacy. Overall Study Objectives:Safety profile of CD33/CD123/CLL-1 CAR-T therapy.Efficacy endpoints (e.g., response rates, survival outcomes).Pharmacokinetic characterization of CAR-T cells (expansion/persistence).
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