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注册号： Registration number：	ChiCTR2400084552
最近更新日期： Date of Last Refreshed on：	2024-05-20 15:10:38
注册时间： Date of Registration：	2024-05-20 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	一项评价输注anti-CD19-CAR-T细胞注射液（anti-CD19-CAR-T细胞）在复发/难治自身免疫性疾病患者中的安全性和有效性的探索性临床研究
Public title：	An exploratory clinical study to evaluating the safety and efficacy of infusion of anti-CD19-CAR-T cells in relapsed/refractory autoimmune diseases
注册题目简写：
English Acronym：
研究课题的正式科学名称：	一项评价输注anti-CD19-CAR-T细胞注射液（anti-CD19-CAR-T细胞）在复发/难治自身免疫性疾病患者中的安全性和有效性的探索性临床研究
Scientific title：	An exploratory clinical study to evaluating the safety and efficacy of infusion of anti-CD19-CAR-T cells in relapsed/refractory autoimmune diseases
研究课题代号(代码)： Study subject ID：
在二级注册机构或其它机构的注册号： The registration number of the Partner Registry or other register：

申请注册联系人：	涂建欣	研究负责人：	孙莉
Applicant：	Jianxin Tu	Study leader：	Li Sun
申请注册联系人电话： Applicant telephone：	+86 182 6772 6068	研究负责人电话： Study leader's telephone：	+86 137 7775 0055
申请注册联系人传真： Applicant Fax：		研究负责人传真： Study leader's fax：
申请注册联系人电子邮件： Applicant E-mail：	Lstujianxin@163.com	研究负责人电子邮件： Study leader's E-mail：	grassandsun@126.com
申请单位网址(自愿提供)： Applicant website(voluntary supply)：		研究负责人网址(自愿提供)： Study leader's website(voluntary supply)：
申请注册联系人通讯地址：	浙江省温州市瓯海区南白象街道上蔡村	研究负责人通讯地址：	浙江省温州市瓯海区南白象街道上蔡村
Applicant address：	Shangcai Village, Nanbaixiang Street, Ouhai District, Wenzhou City, Zhejiang Province	Study leader's address：	Shangcai Village, Nanbaixiang Street, Ouhai District, Wenzhou City, Zhejiang Province
申请注册联系人邮政编码： Applicant postcode：		研究负责人邮政编码： Study leader's postcode：
申请人所在单位：	温州医科大学附属第一医院
Applicant's institution：	The First Affiliated Hospital of Wenzhou Medical University
研究负责人所在单位：	温州医科大学附属第一医院
Affiliation of the Leader：	The First Affiliated Hospital of Wenzhou Medical University

是否获伦理委员会批准：	是/Yes
Approved by ethic committee：	Yes
伦理委员会批件文号： Approved No. of ethic committee：	TXB2023第002号	伦理委员会批件附件： Approved file of Ethical Committee：	查看附件View
批准本研究的伦理委员会名称：	温州医科大学附属第一医院干细胞临床研究伦理委员会
Name of the ethic committee：	Ethics Committee in Clinical Research of the First Affiliated Hospital of Wenzhou Medical University
伦理委员会批准日期： Date of approved by ethic committee：	2023-10-28 00:00:00
伦理委员会联系人：	陈咨苗
Contact Name of the ethic committee：	Zimiao Chen
伦理委员会联系地址：	浙江省温州市瓯海区南白象街道上蔡村
Contact Address of the ethic committee：	Shangcai Village, Nanbaixiang Street, Ouhai District, Wenzhou City, Zhejiang Province
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 577 5557 8027	伦理委员会联系人邮箱： Contact email of the ethic committee：

研究实施负责（组长）单位：

温州医科大学附属第一医院

Primary sponsor：

The First Affiliated Hospital of Wenzhou Medical University

研究实施负责（组长）单位地址：

浙江省温州市瓯海区南白象街道上蔡村

Primary sponsor's address：

Shangcai Village, Nanbaixiang Street, Ouhai District, Wenzhou City, Zhejiang Province

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：	中国	省(直辖市)：	浙江省	市(区县)：	温州市
Country：	China	Province：	Zhejiang Province	City：
单位(医院)：	温州医科大学附属第一医院	具体地址：	浙江省温州市瓯海区南白象街道上蔡村
Institution hospital：	The First Affiliated Hospital of Wenzhou Medical University	Address：	Shangcai Village, Nanbaixiang Street, Ouhai District, Wenzhou City, Zhejiang Province

经费或物资来源：

上海首歌生物科技有限公司

Source(s) of funding：

Shanghai First Song Therapeutics Co., LTD

Target disease：

Systemic Lupus Erythematosus (SLE) ;Sjogren's Syndrome;Systemic Sclerosis;Inflammatory Myopathy;ANCA Associated Vasculitis;Antiphospholipid Syndrome

Target disease code：

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

探索性研究/预试验

Study phase：

0

研究设计：

单臂

Study design：

Single arm

研究目的：

主要目的：评估anti-CD19-CAR-T细胞治疗复发/难治自身免疫性疾病患者的安全性，耐受性和可行性。次要目的： 1.评估anti-CD19-CAR-T细胞输注后体内PK特征； 2.评估anti-CD19-CAR-T细胞输注后体内B细胞恢复特征； 3.评估anti-CD19-CAR-T细胞抗自身免疫性疾病疗效； 4.评估anti-CD19-CAR-T细胞的免疫原性； 5.确定输注anti-CD19-CAR-T细胞患者的细胞因子特征。

Objectives of Study：

The primary objective: To evaluate the safety, tolerability, and feasibility of anti-CD19-CAR-T cell therapy in patients with relapsed/refractory autoimmune diseases. The secondary objectives: 1. To evaluate the PK characteristics of anti-CD19-CAR-T cells post-infusion in vivo; 2. To evaluate the B cell recovery characteristics post-infusion of anti-CD19-CAR-T cells in vivo; 3. To evaluate the efficacy of anti-CD19-CAR-T cells against autoimmune diseases; 4. To evaluate the immunogenicity of anti-CD19-CAR-T cells; 5. To determine the cytokine profile of patients receiving anti-CD19-CAR-T cells.

药物成份或治疗方案详述：

Description for medicine or protocol of treatment in detail：

纳入标准：

1.自愿参加临床研究，本人或法定监护人完全了解、知情本研究并签署知情同意书（ICF），愿意遵循并能完成所有试验程序； 2.年龄为18-65岁； 3.ECOG评分≤2分； 4.预计生存期至少12周； 5.具备良好的静脉通路（进行单采），且无其他血细胞分离禁忌症； 6.患者在筛选时，实验室检查需符合下列要求且筛选血液学评估前7天内未接受过细胞生长因子（长效集落刺激因子（G-CSF/PEG-CSF）需要间隔2周）： 1)中性粒细胞绝对值≥1.0×10^9/L； 2)血红蛋白≥60 g/L（在14天内无红细胞输注的情况下）； 3)血小板≥50×10^9/L； 4)绝对淋巴细胞(ALC) ≥ 0.5×10^9/L； 5)血清总胆红素≤1.5×正常值上限（ULN）； 6)天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）≤2.5×ULN； 7)肌酐<1.5×ULN且内生肌酐清除率≥60 mL/分钟。 7.心脏射血分数≥45%，超声心动图（ECHO）确定无心包积液（少量或生理性的除外），心电图检查结果无临床意义； 8.非吸氧条件下基线氧饱和度>92%； 9.育龄期女性必须有血清或尿液妊娠试验阴性报告（接受过手术绝育的女性或绝经后至少2年的女性不被视为有生育能力的女性）。特异性入选标准：复发难治性系统性红斑狼疮 1. 符合2019年欧洲抗风湿病联盟/美国风湿病学会(EULAR/ACR) SLE的分类标准； 2. 处于疾病中重度活动期，SELENA-SLEDAI评分>6； 3. 至少有一个英岛狼疮评定组指数（BILAG-2004）A类(严重表现)或两个B类 (中度表现)器官评分，或两者兼有； 4. 复发难治性的定义：常规治疗无效或者疾病缓解后再次出现病情活动。常规治疗的定义：使用糖皮质激素（1mg/Kg/d以上）和环磷酰胺，及下列任何一种以上免疫调节药物大于6个月：抗疟药、硫唑嘌呤、吗替麦考酚酯、甲氨蝶呤、来氟米特、他克莫司、环孢素以及生物制剂包括美罗华、贝利尤单抗、泰他西普等。复发难治性干燥综合征 1. 符合原发性干燥综合征的2002年AECG标准或2016年ACR/ EULAR分类标准； 2. 复发难治性的定义：常规治疗无效或者疾病缓解后再次出现病情活动。常规治疗的定义：使用糖皮质激素（1mg/Kg/d以上）和环磷酰胺，及下列任何一种以上免疫调节药物大于6个月：抗疟药、硫唑嘌呤、吗替麦考酚酯、甲氨蝶呤、来氟米特、他克莫司、环孢素以及生物制剂包括美罗华、贝利尤单抗、泰他西普等。复发难治性/进展性弥漫型硬皮病 1. 符合2013年ACR的硬皮病的分类标准，符合弥漫型表现； 2. 合并间质性肺炎：通过胸部HRCT提示磨玻璃样渗出的间质性改变且肺功能检测中FVC或DLCO<70%的预测值； 3. 复发难治性的定义：常规治疗无效或者疾病缓解后再次出现病情活动。常规治疗的定义：使用糖皮质激素（1mg/Kg/d以上）和环磷酰胺，及下列任何一种以上免疫调节药物大于6个月：抗疟药、硫唑嘌呤、吗替麦考酚酯、甲氨蝶呤、来氟米特、他克莫司、环孢素以及生物制剂包括美罗华、贝利尤单抗、泰他西普等； 4. 进展性的定义： a.皮肤进展的定义：mRSS增加>10%； b.肺部疾病进展的定义：FVC降低10%，或FVC降低5%伴DLCO降低15% (OMERACT进展)。复发难治性/进展性炎性肌病 1. 符合2017年EULAR/ACR的炎症性肌病的分类标准（包括DM、PM、ASS和NM）； 2. 有肌肉累及者，MMT-8评分低于142且以下五项核心测量中至少有两项异常发现（PhGA、PtGA或肌外疾病活动度评分≥2分；HAQ总分≥0.25；肌肉酶水平是正常范围上限的1.5倍）； 3. 肌炎抗体阳性； 4. 复发难治性的定义：常规治疗无效或者疾病缓解后再次出现病情活动。常规治疗的定义：使用糖皮质激素（1mg/Kg/d以上）和环磷酰胺，及下列任何一种以上免疫调节药物大于6个月：抗疟药、硫唑嘌呤、吗替麦考酚酯、甲氨蝶呤、来氟米特、他克莫司、环孢素以及生物制剂包括美罗华、贝利尤单抗、泰他西普等； 5. 进展性的定义：短时间内出现快速进展性间质性肺炎。复发难治性ANCA相关性血管炎 1. 符合2022ACR/EULAR关于ANCA血管炎的诊断标准，包括显微镜下多血管炎、肉芽肿性多血管炎、嗜酸性肉芽肿性多血管炎； 2. ANCA相关抗体阳性（MPO-ANCA或PR3-ANCA阳性）； 3. 伯明翰血管炎活动度评分(BVAS）≥15分（总分63分），提示血管炎病情活动； 4. BVAS评估中必须至少有一个主要项目，至少3个次要项目，或至少两个肾项目血尿和蛋白尿； 5. 复发难治性的定义：常规治疗无效或者疾病缓解后再次出现病情活动。常规治疗的定义：使用糖皮质激素（1mg/Kg/d以上）和环磷酰胺，及下列任何一种以上免疫调节药物大于6个月：抗疟药、硫唑嘌呤、吗替麦考酚酯、甲氨蝶呤、来氟米特、他克莫司、环孢素以及生物制剂包括美罗华、贝利尤单抗、泰他西普等。复发难治性/灾难性抗磷脂综合征 1. 符合2006年悉尼修订的原发性抗磷脂综合征的诊断标准； 2. 中高滴度的磷脂抗体阳性（LA、B2GP1或acL的IgG/IgM，12周内检测大于两次阳性）； 3. 复发难治性定义：使用华法林抗凝或替代维生素K拮抗剂的标准治疗(即维持治疗要求的INR）或使用标准治疗剂量低分子肝素(LMWH)，以及使用过激素和环磷酰胺治疗再次血栓形成； 4. 灾难性抗磷脂综合征需要满足以下四个标准： 1）累及三个或三个以上的器官、系统和/或组织； 2）1周内出现症状； 3）组织学证实至少一个器官或组织的小血管阻塞； 4）aPL阳性。

Inclusion criteria

1.Voluntarily participate in clinical research. The person or legal guardian fully understands and informs the research and signs the informed consent form (ICF), and is willing to follow and complete all trial procedures; 2.Aged 18-65 years old; 3.ECOG score ≤ 2 points; 4.Expected survival period is at least 12 weeks; 5.Have good intravenous access (for apheresis) and have no other contraindications to blood cell separation; 6.When screening patients, laboratory tests must meet the following requirements and they must not have received cell growth factors within 7 days before screening hematology assessment (long-acting colony-stimulating factor (G-CSF/PEG-CSF) requires an interval of 2 weeks): 1) Absolute neutrophil count ≥1.0×10^9/L; 2) Hemoglobin ≥60 g/L (without red blood cell transfusion within 14 days); 3) Platelets ≥50×10^9/L; 4) Absolute lymphocytes (ALC) ≥ 0.5×10^9/L; 5) Serum total bilirubin ≤1.5×upper limit of normal (ULN); 6) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×ULN; 7) Creatinine <1.5×ULN and endogenous creatinine clearance ≥60 mL/min. 7. The cardiac ejection fraction is ≥45%, echocardiography (ECHO) confirms that there is no pericardial effusion (except for a small amount or physiological), and the electrocardiogram results have no clinical significance; 8. Baseline oxygen saturation >92% under non-oxygenation conditions; 9. Women of childbearing age must have a negative serum or urine pregnancy test report (women who have undergone surgical sterilization or women who are at least 2 years postmenopausal are not considered women of childbearing potential). Specific Inclusion Criteria: Relapsed and Refractory Systemic Lupus Erythematosus: 1.Comply with the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) SLE classification criteria; 2.In the moderate to severe active stage of the disease, SELENA-SLEDAI score >6; 3.And have at least one British Island Lupus Assessment Group Index (BILAG-2004) Category A (severe performance) or two Category B (moderate performance) organ scores, or both; 4.Definition of relapse and refractory: Conventional treatment is ineffective or disease activity reappears after remission. The definition of routine treatment: the use of glucocorticoids (more than 1 mg/Kg/d) and cyclophosphamide, and any one or more of the following immunomodulatory drugs for more than 6 months: antimalarial drugs, azathioprine, mycophenolate mofetil , methotrexate, leflunomide,tacrolimus,cyclosporine, and biological agents including rituximab, belimumab, tatacept, etc. Relapsed and Refractory Sjogren's Syndrome 1.Meet the 2002 AECG criteria or the 2016 ACR/EULAR classification criteria for primary Sjögren’s syndrome; 2.Definition of relapse and refractory: Conventional treatment is ineffective or disease activity reappears after remission. The definition of routine treatment: the use of glucocorticoids (more than 1 mg/Kg/d) and cyclophosphamide, and any one or more of the following immunomodulatory drugs for more than 6 months: antimalarial drugs, azathioprine, mycophenolate mofetil , methotrexate, leflunomide, tacrolimus, cyclosporine, and biological agents including rituximab, belimumab, tatacept, etc. Relapsed, Refractory/Progressive Diffuse Scleroderma 1.Comply with the 2013 ACR classification criteria for scleroderma and comply with diffuse manifestations; 2.Combined with interstitial pneumonia: chest HRCT shows interstitial changes with ground glass exudation and the predicted value of FVC or DLCO in pulmonary function testing is <70%; 3.Definition of relapse and refractory: Conventional treatment is ineffective or disease activity reappears after remission. The definition of routine treatment: the use of glucocorticoids (more than 1 mg/Kg/d) and cyclophosphamide, and any one or more of the following immunomodulatory drugs for more than 6 months: antimalarial drugs, azathioprine, mycophenolate mofetil , methotrexate, leflunomide, tacrolimus, cyclosporine and biological agents including rituximab, belimumab, tatacept, etc.; 4.Definition of progress: a. Definition of skin progression: mRSS increase >10%; b. Definition of lung disease progression: FVC decreases by 10%, or FVC decreases by 5% and DLCO decreases by 15% (OMERACT progression). Relapsed Refractory/Progressive Inflammatory Myopathy 1.Comply with the 2017 EULAR/ACR classification criteria for inflammatory myopathies (including DM, PM, ASS and NM); 2.For those with muscle involvement, the MMT-8 score is lower than 142 and there are at least two abnormal findings in the following five core measurements (PhGA, PtGA or extramuscular disease activity score ≥ 2 points; HAQ total score ≥ 0.25; muscle enzymes level is 1.5 times the upper limit of the normal range); 3.Myositis antibody positive; 4.Definition of relapse and refractory: Conventional treatment is ineffective or disease activity reappears after remission. The definition of routine treatment: the use of glucocorticoids (more than 1 mg/Kg/d) and cyclophosphamide, and any one or more of the following immunomodulatory drugs for more than 6 months: antimalarial drugs, azathioprine, mycophenolate mofetil , methotrexate, leflunomide, tacrolimus, cyclosporine, and biological agents including rituximab, belimumab, tatacept, etc. 5.Definition of progressive: Rapidly progressive interstitial pneumonia occurring in a short period of time. Relapsed and Refractory ANCA-Associated Vasculitis 1. Meet the 2022 ACR/EULAR diagnostic criteria for ANCA vasculitis, including microscopic polyangiitis, granulomatosis with polyangiitis, and eosinophilic granulomatosis with polyangiitis; 2. Positive ANCA-related antibodies (MPO-ANCA or PR3-ANCA positive); 3. Birmingham Vasculitis Activity Score (BVAS) ≥15 points (total score 63 points), indicating active vasculitis; 4. There must be at least one major item, at least 3 minor items, or at least two renal items in the BVAS assessment: hematuria and proteinuria; 5. Definition of relapse and refractory: Conventional treatment is ineffective or disease activity reappears after remission. The definition of routine treatment: the use of glucocorticoids (more than 1 mg/Kg/d) and cyclophosphamide, and any one or more of the following immunomodulatory drugs for more than 6 months: antimalarial drugs, azathioprine, mycophenolate mofetil , methotrexate, leflunomide, tacrolimus, cyclosporine and biological agents including rituximab, belimumab, tatacept, etc. Relapsed/Refractory/Catastrophic Antiphospholipid Syndrome 1.Meet the diagnostic criteria for primary antiphospholipid syndrome revised in Sydney in 2006; 2.Positive medium-to-high titer phospholipid antibodies (LA, B2GP1 or acL IgG/IgM, more than two positive tests within 12 weeks); 3.Definition of relapse and refractory: use of warfarin anticoagulation or standard treatment instead of vitamin K antagonists (i.e., maintenance of the INR required for treatment) or use of standard therapeutic doses of low molecular weight heparin (LMWH), as well as use of hormones and cyclophosphamide treatment Recurrence of thrombosis; 4.Catastrophic antiphospholipid syndrome requires the following four criteria: 1)Involving three or more organs, systems and/or tissues; 2)Symptoms appear within 1 week; 3)Histology confirms small blood vessel obstruction in at least one organ or tissue; 4)aPL positive.

排除标准：

1.有活动性中枢神经系统疾病，如癫痫、脑血管缺血/出血、痴呆、小脑疾病，或任何有中枢神经系统受累的自身免疫性疾病； 2.存在或怀疑存在真菌、细菌、病毒或其他感染，且未得到控制或需要静脉注射抗菌素进行治疗；允许存在简单的尿路感染和无并发症的细菌性咽喉炎等； 3.患有乙型肝炎（乙肝病毒表面抗原且乙肝DNA>1000拷贝/ml）或丙型肝炎（丙肝抗体检测阳性）；梅毒感染（抗体阳性）；人类免疫缺陷病毒（HIV）感染； 4.既往用药： 1)CD19靶向治疗； 2)入组前4周内注射活疫苗； 3)入组前4周内使用的免疫抑制性抗体（如抗CD20、抗肿瘤坏死因子、抗白细胞介素6或抗白细胞介素6受体）； 4)单采前5个半衰期内使用免疫刺激或免疫增强剂治疗（如他克莫司、环孢素、干扰素-α、干扰素-β、IL-2）； 5)入组前2周内曾使用过全身性细胞毒性药物，包括每日或每周的低剂量维持性化疗，（环磷酰胺、伊磷酰胺、苯达莫司汀、氯氨蝶呤或美法仑、长春新碱等）； 6)单采前14天内的长效生长因子（如聚乙二醇非格司亭）或单采前5天内的短效生长因子或用于细胞动员的药物（如粒细胞集落刺激因子/非格司亭、普乐沙福)； 7)入组前4天内必须避免使用药理学剂量的皮质类固醇治疗（>10毫克/天的泼尼松或同等剂量的其他皮质类固醇）和其他免疫抑制性药物。 5.入组前12个月内有心肌梗塞、心脏血管成形术或支架植入术、不稳定心绞痛或其他临床意义的心脏疾病史； 6.伴有骨髓衰竭的遗传综合征病史，如范可尼贫血、科斯特曼综合征、斯瓦赫曼-钻石综合征等； 7.入组前6个月内有症状性深静脉血栓或肺栓塞需要全身抗凝史。受试者需要服用预防性抗凝药物； 8.既往或现在同时患有其它恶性肿瘤（皮肤基底细胞癌、乳腺/宫颈原位癌和其它在过去五年内没有治疗也得到有效控制的恶性肿瘤除外）； 9.筛选前30天内使用其他研究性医药产品。 10.怀孕或哺乳期的育龄妇女（因为化疗对胎儿或婴儿有潜在的危险影响）； 11.从签署知情同意书开始至完成末次研究药物给药后6个月内，不愿意实行节育的男女受试者； 12.任何可能干扰评估研究安全性或疗效的医疗活动； 13.根据研究者的判断，受试者不太可能完成所有方案要求的研究访视或程序，包括随访或遵守参与研究的要求； 14.既往使用过任何CAR-T细胞产品或其他基因修饰的T细胞疗法者。特异性排除标准：复发难治性系统性红斑狼疮 1. 合并神经精神狼疮； 2. 血栓性血小板减少性紫癜(TTP)/微血栓性血管病(TMA)。复发难治性干燥综合征 1. 合并肝硬化； 2. 合并再生障碍性贫血(AA)、骨髓增生异常综合征(MDS)或其他骨髓增生性疾病(MPD)； 3. 药物引起的血小板减少； 4. 血栓性血小板减少性紫癜(TTP)/微血栓性血管病(TMA)。复发难治性/进展性弥漫型硬皮病 1. 纽约心功能IV级； 2. 存在中度至重度肺动脉高压(超声心动图平均肺动脉压>40 mmHg)； 3. FVC <45%预测值； 4. DLCO <40%预测值； 5. HRCT上的显著异常不是由SSc引起的； 6. 持续原因不明的血尿(高倍镜下5个红细胞)或肌酐清除率<40ml/min； 7. 既往有自体干细胞移植的患者； 8. 存在肾危象迹象； 9. 活跃性胃窦血管扩张。复发难治性/进展性炎性肌病 1. 药物诱导的肌炎； 2. 包涵体肌炎； 3. 肿瘤相关肌炎（确诊肿瘤后2年内发生的肌炎）。复发难治性ANCA相关性血管炎 1. 估计肾小球滤过率(eGFR)<15 mL/min/1.73 m2； 2. 如果患者有肺泡出血，需要进行有创肺通气，预计持续时间超过筛查时间； 3. 筛查期需要透析或血浆交换； 4. 接受过肾移植。复发难治性/灾难性抗磷脂综合征 1. 产科APS； 2. 其他CTD合并的APS； 3. APS神经系统累及。

Exclusion criteria：

1.Have active central nervous system diseases, such as epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease involving the central nervous system; 2.Fungal, bacterial, viral or other infections exist or are suspected and are not controlled or require intravenous antibiotic treatment; simple urinary tract infections and uncomplicated bacterial pharyngitis are allowed; 3.Suffering from hepatitis B (hepatitis B virus surface antigen and hepatitis B DNA >1000 copies/ml) or hepatitis C (positive hepatitis C antibody test); syphilis infection (antibody positive); human immunodeficiency virus (HIV) infection; 4.Past medication: 1) CD19 targeted therapy; 2) Inject live vaccines within 4 weeks before enrollment; 3) Immunosuppressive antibodies (such as anti-CD20, anti-tumor necrosis factor, anti-interleukin 6 or anti-interleukin 6 receptor) used within 4 weeks before enrollment; 4) Use immunostimulatory or immune enhancer treatment (such as tacrolimus, cyclosporine, interferon-α, interferon-β, IL-2) within the 5 half-lives before apheresis; 5) Have used systemic cytotoxic drugs within 2 weeks before enrollment, including daily or weekly low-dose maintenance chemotherapy (cyclophosphamide, ifosfamide, bendamustine, clotrexate or Melphalan, vincristine, etc.); 6) Long-acting growth factors within 14 days before apheresis (such as pegfilgrastim) or short-acting growth factors within 5 days before apheresis or drugs used for cell mobilization (such as granulocyte colony-stimulating factor/non- Gestin, Plexafor); 7) The use of pharmacological doses of corticosteroids (>10 mg/day of prednisone or equivalent doses of other corticosteroids) and other immunosuppressive drugs must be avoided within 4 days before enrollment. 5.Have a history of myocardial infarction, cardiac angioplasty or stent implantation, unstable angina or other clinically significant heart diseases within 12 months before enrollment; 6.History of genetic syndromes associated with bone marrow failure, such as Fanconi anemia, Kosterman syndrome, Swachmann-Diamond syndrome, etc.; 7.History of symptomatic deep vein thrombosis or pulmonary embolism requiring systemic anticoagulation within 6 months before enrollment. Subjects need to take prophylactic anticoagulant drugs; 8.Have suffered from other malignant tumors in the past or at the same time (except for basal cell carcinoma of the skin, carcinoma in situ of the breast/cervix and other malignant tumors that have been effectively controlled without treatment in the past five years); 9.Use of other investigational pharmaceutical products within 30 days before screening; 10.Women of childbearing age who are pregnant or breastfeeding (because chemotherapy has potentially dangerous effects on the fetus or baby); 11.Male and female subjects who are unwilling to undergo birth control within 6 months from the signing of the informed consent form to the completion of the last administration of the study drug; 12.Any medical activity that may interfere with the evaluation of the safety or efficacy of the study; 13.According to the investigator's judgment, the subject is unlikely to complete all study visits or procedures required by the protocol, including follow-up visits or comply with the requirements for participation in the study; 14.Those who have used any CAR-T cell products or other genetically modified T cell therapies in the past. Specific Exclusion Criteria: Relapsed and Refractory Systemic Lupus Erythematosus: 1.Combined with neuropsychiatric lupus; 2.Thrombotic thrombocytopenic purpura (TTP)/microthrombotic vasculopathy (TMA). Relapsed and Refractory Sjogren's Syndrome 1.Combined with liver cirrhosis; 2.Combined with aplastic anemia (AA), myelodysplastic syndrome (MDS) or other myeloproliferative diseases (MPD); 3.Drug-induced thrombocytopenia; 4.Thrombotic thrombocytopenic purpura (TTP)/microthrombotic vasculopathy (TMA). Relapsed, Refractory/Progressive Diffuse Scleroderma 1.New York heart function class IV; 2.There is moderate to severe pulmonary hypertension (mean pulmonary artery pressure on echocardiography >40 mmHg); 2.FVC <45% predicted value; 3.DLCO <40% predicted value; 4.Significant abnormalities on HRCT are not caused by SSc; 5.Persistent unexplained hematuria (5 red blood cells under high power) or creatinine clearance <40ml/min; 6.Patients who have had autologous stem cell transplantation in the past; 7.There are signs of renal crisis; 8.Active antral vasodilation. Relapsed Refractory/Progressive Inflammatory Myopathy 1.Drug-induced myositis 2.Inclusion body myositis; 3.Tumor-related myositis (myositis occurring within 2 years after tumor diagnosis). Relapsed and Refractory ANCA-Associated Vasculitis 1.Estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m2; 2.If the patient has alveolar hemorrhage, invasive pulmonary ventilation is required and the duration is expected to exceed the screening time; 3.Dialysis or plasma exchange is required during the screening period; 4.Have received a kidney transplant. Relapsed/Refractory/Catastrophic Antiphospholipid Syndrome 1. Obstetric APS; 2. APS merged with other CTDs; 3. APS involves the nervous system.

研究实施时间：

Study execute time：

从 From 2024-05-07 00:00:00至 To 2027-05-06 00:00:00

征募观察对象时间：

Recruiting time：

从From 2024-05-27 00:00:00 至 To 2026-05-05 00:00:00

干预措施：

Interventions：

组别：	治疗组	样本量：	9
Group：	Treatment group	Sample size：	9
干预措施：	输注anti-CD19-CAR-T细胞注射液	干预措施代码：
Intervention：	Infusion of anti-CD19-CAR T cell injection	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	浙江	市(区县)：
Country：	China	Province：	Zhejiang Province	City：
单位(医院)：	温州医科大学附属第一医院	单位级别：	三甲
Institution hospital：	The First Affiliated Hospital of Wenzhou Medical University	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	剂量限制毒性 (DLT)发生率	指标类型：	主要指标
Outcome：	Incidence of dose-limiting toxicity	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	不良事件的类型、频率和严重程度以及实验室检查异常	指标类型：	主要指标
Outcome：	Laboratory abnormalities and type, frequency and severity of adverse events	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	可成功制造所需剂量anti-CD19-CAR-T细胞的受试者百分比	指标类型：	主要指标
Outcome：	Proportion of patients for whom a CAR-T cell product could be prepared Percentage of subjects for whom the desired dose of anti-CD19 -CAR-T cells can be successfully manufactured	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	CRS和神经毒性的发生率和分级	指标类型：	次要指标
Outcome：	Incidence and grading of CRS and neurotoxicity	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	血液样本中anti-CD19-CAR-T细胞的水平和持久性	指标类型：	次要指标
Outcome：	The level and persistence of anti-CD19-CAR-T cells in blood samples	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	疾病缓解率	指标类型：	次要指标
Outcome：	Disease remission rate	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	抗CD19抗体的发生率	指标类型：	次要指标
Outcome：	Incidence of anti-CD19 antibodies	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	血清中细胞因子水平，包括IL-6、IL-10、IFN-γ、TNF-α浓度	指标类型：	次要指标
Outcome：	Cytokine levels in serum, including IL-6, IL-10, IFN-γ, and TNF-α concentrations	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：	血液	组织：
Sample Name：	Blood	Tissue：
人体标本去向	使用后销毁	说明
Fate of sample：	Destruction after use	Note：

征募研究对象情况：

Recruiting status：

尚未开始

Not yet recruiting

年龄范围：

Participant age：

最小 Min age	18	岁 years
最大 Max age	65	岁 years

性别：

男女均可

Gender：

Both

随机方法（请说明由何人用什么方法产生随机序列）：

无

Randomization Procedure (please state who generates the random number sequence and by what method)：

None

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

公开/Public

盲法：
Blinding：
试验完成后的统计结果（上传文件）：	点击下载
Calculated Results after the Study Completed(upload file)：	download

是否共享原始数据： IPD sharing	No
共享原始数据的方式（说明：请填入公开原始数据日期和方式，如采用网络平台，需填该网络平台名称和网址）：	无
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	None
数据采集和管理（说明：数据采集和管理由两部分组成，一为病例记录表(Case Record Form, CRF)，二为电子采集和管理系统(Electronic Data Capture, EDC)，如ResMan即为一种基于互联网的EDC：	将使用EDC采集和管理数据
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	Data will be collected and managed using the EDC.
数据与安全监察委员会： Data and Safety Monitoring Committee：	暂未确定/Not yet
注册人： Name of Registration：	2024-05-20 15:10:32