肿瘤细胞治疗研究
英文原题：Anti-CD19 Chimeric Antigen Receptor Modified T-cell (CAR-T) Therapy for Treatment of B-cell Hematological Malignancies
Anti-CD19 Chimeric Antigen Receptor Modified T-cell (CAR-T) Therapy for Treatment of B-cell Hematological Malignancies
⚠ 该试验的登记信息已有 28 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 II 期注册临床试验，评估细胞治疗用于淋巴瘤、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 20 例。试验地点：中国 · 香港（共 1 个中心，其中中国 1 个）。登记号：NCT06462248。
不限性别 · ≥ 1 Year
急性淋巴细胞白血病（ALL） • 复发或难治性CD19阳性B细胞ALL患儿或成人，年龄0至60岁。患者可处于首次或后续复发、既往干细胞移植后复发，或持续微小残留病（MRD）阳性状态。 • 筛查时，年龄>16岁者ECOG体能状态评分≤2；年龄≤16岁者Lansky体能状态评分>50。 • 异基因干细胞移植后B-ALL患者须在移植3个月后入组，且已停用免疫抑制治疗至少1个月。 • 活动性白血病患者因病情出现显著器官功能损害，无法耐受常规化疗。 • 有生育能力女性须在单采前妊娠试验阴性。 B细胞淋巴瘤 • 组织学确诊为难治性弥漫大B细胞淋巴瘤、原发纵隔B细胞淋巴瘤、转化型滤泡性淋巴瘤或WHO分类中的其他B细胞淋巴瘤。 • 诊断或复发时取得的组织样本已确认CD19阳性。 • 至少接受过两种既往治疗，其中至少一种为强化全身治疗。 • 自体干细胞移植后12个月内疾病进展或复发。 • 筛查时，年龄>16岁者ECOG体能状态评分≤2；年龄≤16岁者Lansky体能状态评分>50。 • 器官功能足以耐受CAR-T细胞治疗。 • 有生育能力女性须在单采前妊娠试验阴性。 两个队列共同的排除标准 • 活动性感染。 • 异基因移植后B-ALL患者存在活动性移植物抗宿主病（GVHD）或正在接受免疫抑制治疗。 • 异基因移植后近期接受供者淋巴细胞输注（DLI），且DLI与CAR-T输注间隔不足6周。 • 当前患有自身免疫病，或有可能累及中枢神经系统（CNS）的自身免疫病史。 • 存在活动性、具有临床意义的CNS功能障碍，包括但不限于未控制的癫痫、脑血管缺血或出血、痴呆、瘫痪。 • HBsAg阳性、HCV RNA阳性或HIV感染。 • 肺功能：呼吸困难为1级，且室内空气下脉搏血氧饱和度>91%。 • 心功能：超声心动图显示短轴缩短率<28%或左心室射血分数<45%。 • 肾功能：肌酐清除率<50 mL/min/1.73 m²。 • 肝功能：血清胆红素>正常值上限（ULN）的3倍，或AST/ALT>5倍ULN；若研究者判断由白血病肝浸润所致则除外。 • 研究者判断疾病进展迅速，可能妨碍完成研究治疗。
Inclusion Criteria: Acute Lymphoblastic Leukaemia * Paediatric or adult patients with relapsed or refractory CD19+ B cell ALL. (Age 0-60 years). Patients should be in first or subsequent relapse, or relapse after prior stem cell transplant, or persistent Minimal Residual Disease (MRD) positive disease * ECOG performance score of ≤2 if \>16 years old, or Lansky performance score of \>50 if ≤16 years old at screening * Post allogeneic stem cell transplant patients with B cell ALL will be eligible \> 3 months after transplant and off immunosuppression for at least 1 month. * Patients with active leukaemia who developed significant organ impairment that cannot tolerate conventional chemotherapy, * For women of childbearing potential, a negative pregnancy test prior to apheresis B-cell lymphoma * Patients with histologically confirmed refractory Diffuse Large B-cell Lymphoma, primary mediastinal B cell lymphoma or transformed follicular lymphoma or other B-cell lymphoma according to WHO classification * Confirmed CD19 positivity status in tissue sample obtained at diagnosis or relapse * Received at least two prior treatment which must include at least one intensive systemic therapy. * Disease progression or relapsed disease within 12 months after autologous stem cell transplant * ECOG performance score of ≤2 if \>16 years old, or Lansky performance score of \>50 if ≤16 years old at screening * Has sufficient organ function to tolerate treatment with CAR-T cell therapy * For women of childbearing potential, a negative pregnancy test prior to apheresis Exclusion criteria of both cohorts * Patients with active infection * Patients with B cell ALL post allogeneic transplant with active GVHD or on immunosuppression * Recent donor lymphocyte infusion (DLI) after allogeneic transplant, less than 6 weeks between DLI and CAR T infusion * Current autoimmune disease, or history of autoimmune disease with potential CNS involvement * Active clinically significant CNS dysfunction (including but not limited to uncontrolled seizure disorders, cerebrovascular ischaemia or haemorrhage, dementia, paralysis) * Patients who are positive for HBsAg, HCV RNA positive or with HIV infection * Pulmonary function: Grade 1 dyspnea and pulse oxygenation \> 91% on room air * Cardiac function: Fractional shortening \<28% or left ventricular ejection fraction \<45% by echocardiography. * Renal function: Creatinine clearance \<50 mL/min/1.73 m2 * Liver function: Patients with a serum bilirubin \>3 times upper limit of normal or an AST or ALT \> 5 times upper limit of normal, unless due to leukaemic liver infiltration in the estimation of the investigator * Rapidly progressive disease that in the estimation of the investigator would compromise ability to complete study therapy.
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：Production efficiency of CAR-T cell manufacturing · At least 90% of patients enrolled should be able to achieve successful production of CAR T cells as deomonstrated by CAR-T cell proliferation and persisteance of CAR-T cells in recipients for at least one month after infusion · 18 months
次要终点：survival outcome
单臂、开放标签II期研究。
CAR-T疗法已作为商业化产品用于治疗复发/难治性急性淋巴细胞白血病及B细胞淋巴瘤，但由于费用高昂，患者获得该疗法的机会有限。因此，亟需开发具有成本效益的封闭式CAR-T细胞制备系统，使CAR-T能够在治疗现场制备。香港生物科技研究院已建立符合GMP要求的认证设施，并使用Prodigy系统制备临床应用的CAR-T细胞。威尔斯亲王医院和香港儿童医院将开展II期临床试验，以确认本地制备CAR-T细胞产品的疗效和安全性。
CAR-T therapy is now available as a commercial product for treatment of relapsed /refractory acute lymphoblastic leukaemia and B-lymphoma. There is limited access to this new treatment as the product is very expensive. It is imperative to develop cost effective, closed circuit manufacturing systems for CAR-T cells to make CAR-T cells a point-of care production option. Hong Kong Institute of Biotechnology has established a certified GMP facility and utilize the Prodigy system to manufacture CAR-T cells for clinical application. Prince of Wales Hospital and Hong Kong Children's Hospital will conduct the phase II clinical trial to confirm the efficacy and safety of local manufactured CAR-T cell product.
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