ChiCTR1900021038 版本V1.4 版本创建时间2019/1/26 11:08:38 中国临床试验注册中心

审核状态:

Project audit state:

通过审核

Successful

注册号:

Registration number:

ChiCTR1900021038 

最近更新时间:

Date of Last Refreshed on:

2019/1/26 11:06:26 

注册号状态:

预注册  

Registration Status:

Prospective registration  

填写语言:

中文和英文  

Language:

Chinese And English  

注册题目:

脐带血造血干细胞移植治疗重型再生障碍性贫血多中心研究 

Public title:

A multicenter study for umblical cord blood transplantation for acquired severe aplastic anaemia  

注册题目简写:

 

Public title acronym:

 

研究课题的正式科学名称:

脐带血造血干细胞移植治疗重型再生障碍性贫血多中心研究 

Scientific title:

A multicenter study for umblical cord blood transplantation for acquired severe aplastic anaemia  

研究课题的正式科学名称简写:

 

Scientific title acronym:

 

研究课题代号(代码):

Study subject ID:

 

在其它机构的注册号:

Secondary ID:

 

申请注册联系人:

汤宝林 

研究负责人:

孙自敏 

Applicant:

Baolin Tang 

Study leader:

Zimin Sun 

申请注册联系人电话:

Applicant telephone:

+86 13856901277 

研究负责人电话:

Study leader's telephone:

+86 551 62282992 

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:

zwcrystalbl@163.com 

研究负责人电子邮件:

Study leader's E-mail:

zmsun_vip@163.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:

安徽省合肥市庐江路17号 

研究负责人通讯地址:

安徽省合肥市庐江路17号 

Applicant address:

17 Lujiang Road, Luyang District, Hefei, Anhui, China 

Study leader's address:

17 Lujiang Road, Luyang District, Hefei, Anhui, China 

申请注册联系人邮政编码:

Applicant postcode:

230001 

研究负责人邮政编码:

Study leader's postcode:

230001 

申请人所在单位:

中国科学技术大学附属第一医院 

Applicant's institution:

The First Affiliated Hospital of USTC, Division of Life Sciences and Medcine, University of Science and Technology of China 

是否获伦理委员会批准:

是 

Approved by ethic committee:

Yes 

伦理委员会批件文号:

Approved No. of ethic committee:

ChiECRCT-20180217 

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:

中国注册临床试验伦理审查委员会 

Name of the ethic committee:

China Committee for Ethical Review of Registered Clinical Trials 

伦理委员会批准日期:

Date of approved by ethic committee:

2013-08-26 

国家FDA批准文号:

Approved No. of SFDA:

国家FDA批准附件:

Approved file of SFDA:

国家FDA批准日期:

Date of approved by SFDA:

研究实施负责(组长)单位:

中国科学技术大学附属第一医院 

Primary sponsor:

The First Affiliated Hospital of USTC, Division of Life Sciences and Medcine, University of Science and Technology of China 

研究实施负责(组长)单位地址:

安徽省合肥市庐江路17号 

Primary sponsor's address:

17 Lujiang Road, Luyang District, Hefei, Anhui, China 

试验主办单位(项目批准或申办者):

Secondary sponsor:

国家:

中国

省(直辖市):

安徽

市(区县):

合肥

Country:

China

Province:

Anhui

City:

Hefei

单位(医院):

中国科学技术大学附属第一医院

具体地址:

安徽省合肥市庐江路17号

Institution
hospital:

The First Affiliated Hospital of USTC, Division of Life Sciences and Medcine, University of Science and Technology of China

Address:

17 Lujiang Road, Luyang District

国家:

中国

省(直辖市):

天津

市(区县):

Country:

China

Province:

Tianjin

City:

单位(医院):

中国医学科学院血液病医院

具体地址:

和平区南京路288号

Institution
hospital:

Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & PUMC

Address:

288 Nanjing Road, Heping District

国家:

中国

省(直辖市):

上海

市(区县):

Country:

China

Province:

Shanghai

City:

单位(医院):

上海市第一人民医院

具体地址:

上海市虹口区海宁路100号

Institution
hospital:

Shanghai General Hospital

Address:

100 Haining Road, Hongkou District

国家:

中国

省(直辖市):

北京

市(区县):

Country:

China

Province:

Beijing

City:

单位(医院):

北京市航天中心医院

具体地址:

北京市海淀区玉泉路15号

Institution
hospital:

Beijing Aerospace Center Hospital

Address:

15 Yuquan Road, Haidian District

国家:

中国

省(直辖市):

江苏

市(区县):

Country:

China

Province:

Jiangsu

City:

单位(医院):

东南大学附属中大医院

具体地址:

南京市鼓楼区湖南路丁家桥87号

Institution
hospital:

Zhongda Hospital Affiliated to Southeast university

Address:

87 Dingjiaqiao, Hunan Road, Gulou District

国家:

中国

省(直辖市):

福建

市(区县):

福州

Country:

China

Province:

Fujian

City:

Fuzhou

单位(医院):

福建医科大学附属协和医院

具体地址:

福建省福州市新权路29号

Institution
hospital:

Fujian Medical University Union Hospital

Address:

29 Xinquan Road

国家:

中国

省(直辖市):

广州

市(区县):

Country:

China

Province:

Guangzhou

City:

单位(医院):

广州市第一人民医院

具体地址:

广州市越秀区盘福路1号

Institution
hospital:

the first people's hospital of Guangzhou

Address:

1 Panfu Road, Yuexiu District

国家:

中国

省(直辖市):

湖南

市(区县):

Country:

China

Province:

Hunan

City:

单位(医院):

湖南省郴州市第一人民医院

具体地址:

郴州市罗家井102号

Institution
hospital:

the First People's Hospital of Chenzhou

Address:

102 Luojiajing, Chenzhou

国家:

中国

省(直辖市):

云南

市(区县):

昆明

Country:

China

Province:

Yunnan

City:

Kunming

单位(医院):

解放军昆明总医院

具体地址:

昆明市大观路212号

Institution
hospital:

Kunming General Hospital of PLA

Address:

212 Daguan Road

国家:

中国

省(直辖市):

广东

市(区县):

Country:

China

Province:

Guangdong

City:

单位(医院):

南方医科大学南方医院

具体地址:

广东省广州市白云区广州大道北路1838号

Institution
hospital:

Southern Hospital Affiliated to Southern Medical University

Address:

1838 Guangzhou Avenue Road North, Baiyun District

国家:

中国

省(直辖市):

山东

市(区县):

济南

Country:

China

Province:

Shandong

City:

Jinan

单位(医院):

山东大学齐鲁医院

具体地址:

济南市文化西路107号

Institution
hospital:

Qilu Hospital Affiliated to Shandong University

Address:

107 Cultural West Road

国家:

中国

省(直辖市):

上海

市(区县):

Country:

China

Province:

Shanghai

City:

单位(医院):

上海新华医院

具体地址:

上海市杨浦区控江路1665号

Institution
hospital:

Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Address:

1665 Zhenjiang Road, Yangpu District

国家:

中国

省(直辖市):

安徽

市(区县):

芜湖

Country:

China

Province:

Anhui

City:

Wuhu

单位(医院):

皖南医学院第一附属医院

具体地址:

安徽省芜湖市赭山西路2号

Institution
hospital:

The First Affiliated Hospital of Wannan Medical College

Address:

2 Cheshan Road

经费或物资来源:

中央高校基本科研业务费专项资金 

Source(s) of funding:

the Fundamental Research Funds for the Central Universities 

研究疾病:

重型再生障碍性贫血 

Target disease:

Acquired severe aplastic anaemia  

研究疾病代码:

 

Target disease code:

 

研究类型:

观察性研究 

Study type:

Observational study 

研究所处阶段:

治疗新技术临床试验 

Study phase:

New Treatment Measure Clinical Study 

研究目的:

评价脐带血造血干细胞移植治疗免疫抑制治疗无效的重型再生障碍性贫血的安全性和有效性。  

Objectives of Study:

To evaluate the safety and validity of umbilical cord blood stem cell transplantation for the treatment of severe aplastic anemia failure to immunosuppressive therapy  

研究设计:

单臂 

Study design:

Single arm 

纳入标准:

1.明确诊断为重型再生障碍性贫血(Camitta标准): (1)骨髓细胞增生程度<正常的25%;如≥正常的25%但<50%,则残存的造血细胞应<30%。 (2)血常规:需具备下列三项中的两项:ANC<0.5×109/L;网织红细胞绝对值<20×109/L;PLT<20×109/L; 2.年龄≦50岁,性别不限; 3.免疫抑制治疗(抗人胸腺细胞球蛋白和/或环孢素A为主的治疗超过120天)无效; 4.无可用的HLA全相合同胞供者或10/10 HLA位点相合的非亲缘造血干细胞移植供者进行移植; 5.具有可用于移植的替代供者:接受脐血移植的患者须有HLA高分辨配型(A、B、 DR)相合位点4/6以上(或者A、B、C、DR 5/8相合以及A、B、C、DR 4/8相合但是符合半相合配型要求)、冷冻前有核细胞数≧3.5×107/kg、CD34+细胞数≧1.2×107/kg以及CFU-GM≧的脐血可用于移植; 6.患者及家属或其监护人同意研究并签署知情同意书; 7.无严重脏器功能衰竭;移植前 2 周内 GPT、GGT、胆红素小于正常值上限的 2 倍,血肌酐小于正常值上限的 2倍,心肌酶小于正常值上限的 2倍;(1)心脏:休息时左心室射血分数(LVEF)大于40%。对于小于13岁的患者,超声心动图缩短LFEF的缩短分数(SF)超过26%。(2)肝:总胆红素<相应年龄正常值上限(ULN)的 3倍;丙氨酸转氨酶(ALT)和天门冬氨酸氨基转移酶(AST)<相应年龄ULN 5倍。(3)肾:≧13岁的患者:血肌酐小于ULN的 2倍;预计肌酐清除率>50ml/min(使用Cockcroft-Gault公式和实际体重)。<13岁的患者:更新的Schwartz公式估计肾小球滤过率(GFR)为90毫升/分钟/1.73 m2。如果估计GFR<90 mL/min/1.73 m2,则肾功能必须通过24小时肌酐清除率或核GFR测定,且必须为50毫升/分钟/1.73 m2。(4)肺:≧13岁患者:肺一氧化碳弥散量(DLCO)(校正/调整血红蛋白)>40%,用力呼气量1秒(FEV1)>50%预测值(不加支气管扩张剂)和用力肺活量(FVC)>50%预测值。对于13岁以下的患者,由于年龄或发育能力无法进行肺功能检查(PFT):(1)没有休息时呼吸困难的证据,(2)室内空气中不需要吸氧。 8.Karnofsky评分≥ 60%; 生育年龄的女性妊娠试验必须为阴性,且同意在治疗期间及随后的一年内使用有效的避孕措施。 

Inclusion criteria

1. Confirmed diagnosis of SAA, either from initial diagnosis or follow-up assessments, defined as: Bone marrow cellularity < 25% or marrow cellularity < 50% but with < 30% residual hematopoietic cells. Two out of three of the following (in peripheral blood): Neutrophils < 0.5 x10^9/L, Platelets < 20 x10^9/L, or Reticulocyte count < 20 x10^9/L; 2. Patient is < 50 years of age at time of enrollment and the sex is not limited; 3. Failed at least one trial of immunosuppressive therapy (IST) by being refractory or having relapsed. IST could have included ATG based regimens, calcineurin inhibitors and/or other higher dose therapy directed at the treatment of primary SAA; 4. No suitable fully matched related (6/6 match for human leukocyte antigen (HLA)-A and B at intermediate or high resolution and DRB1 at high resolution using DNA-based typing) or unrelated donor (8/8 match for HLA-A, B, C, and DRB1 at high resolution using DNA-based typing) available. Search for an unrelated donor and enrollment on this protocol may be abandoned if the clinical situation dictates an urgent transplant in the best medical judgment of the treating provider. The definition of clinical urgency may include a low likelihood of identifying a suitable matched unrelated donor within 6-8 weeks from referral and the medical need to choose a donor without further delay beyond that time. 5. Available alternative donor: Cord blood unit(s) must be matched at a minimum of 4/6 to the recipient at HLA-A and B at low resolution using DNA-based typing and HLA-DRB1 at high resolution using DNA-based typing. Based on a published report from Eurocord, for single unit transplantation, the single unit pre-cryopreserved total nucleated cell (TNC) dose must be a minimum of 3.5 x10^7/kg recipient weight; 6. Patient and/or legal guardian must sign informed consent for HSCT; 7. Adequate organ function defined as: Cardiac: Left ventricular ejection fraction (LVEF) at rest ≥ 40%. For patients aged < 13 years, shortening fraction (SF) ≥ 26% by echocardiogram or Multi Gated Acquisition Scan (MUGA) may be substituted for LVEF. Hepatic: Total bilirubin < 3.0 x the upper limit of normal (ULN) for age (patients who have been diagnosed with Gilbert's Disease are allowed to exceed this limit) and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 5.0 x ULN for age. Renal: For patients > 13.0 years of age at the time of enrollment: estimated creatinine clearance > 50 mL/minute (using the Cockcroft-Gault formula and actual body weight). For patients < 13.0 years of age at enrollment: Glomerular Filtration Rate (GFR) estimated by the updated Schwartz formula ≥ 90 mL/min/1.73 m2. If the estimated GFR is < 90 mL/min/1.73 m^2, then renal function must be measured by 24-hour creatinine clearance or nuclear GFR, and must be > 50 mL/min/1.73 m^2. Pulmonary: For patients > 13.0 years of age: Diffusing capacity of the lung for carbon monoxide (DLCO) (corrected/adjusted for hemoglobin) > 40% and forced expiratory volume in one second (FEV1) > 50% predicted (without administration of bronchodilator) and forced vital capacity (FVC) > 50% predicted. For patients < 13.0 years of age unable to perform pulmonary function tests (PFT) due to age or developmental ability: (1) no evidence of dyspnea at rest and (2) no need for supplemental oxygen and (3) O2 saturation > 92% on room air at sea level (with lower levels allowed at higher elevations per established center standard of care (e.g., Utah, 4,200 feet above sea level, does not give supplemental oxygen unless below 90%)); 8. Karnofsky or Lansky performance status ≥ 60%; 9. Females and males of childbearing potential must agree to practice 2 effective methods of contraception at the same time or agree to abstinence.  

排除标准:

1. 遗传性骨髓衰竭性疾病; 2. 针对脐血的HLA-A、B、C、DRB1或 DPB1位点特异性HLA抗体阳性,固相荧光法测定平均荧光强度(MFI)>1000; 3. 既往曾接受过异基因造血干细胞移植或实体器官移植治疗; 4. 未控制的细菌、病毒或真菌感染。未控制的定义是充分抗感染治疗下没有临床改善或进展; 5. HIV感染或活动性乙型或丙型病毒性肝炎; 6. 孕妇或处于哺乳期的产妇; 7. 接受移植治疗前3年内有原发性恶性肿瘤病史(基底细胞癌切除或原位宫颈癌治疗外); 8. 移植前2周内应用ATG治疗; 9. 药物依赖者;未控制的精神疾病受试者;认知功能障碍者; 10. 3个月内参加其他相似的临床研究者; 11. 研究者认为不适合入组者(如预计患者会因经费等问题无法坚持治疗者)。  

Exclusion criteria:

1. Inherited bone marrow failure syndromes; 2. Presence of anti-donor HLA antibodies (positive anti-donor HLA antibody is defined as a positive cross-match test of any titer by complement-dependent cytotoxicity or flow cytometric testing or the presence of anti-donor HLA antibody to the high expression loci HLA-A, B, C, DRB1, or DPB1 with mean fluorescence intensity (MFI) > 1000 by solid phase immunoassay); 3. Prior allogeneic stem cell transplant or prior solid organ transplant; 4. Uncontrolled bacterial, viral, or fungal infection at the time of enrollment. Uncontrolled is defined as currently taking medication and with progression or no clinical improvement on adequate medical treatment; 5. Seropositive for the human immunodeficiency virus (HIV) or active Hepatitis B or C determined by a detectable viral load of HBV or HCV; 6. Female patients who are pregnant (per institutional practice) or breast-feeding; 7. Prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ; 8. ATG within 2 weeks of enrollment; 9. Drug addicts; uncontrolled mental disorders subjects; cognitive dysfunction; 10. Participate in other similar clinical studies within 3 months; 11. Researchers consider that patients who are not suitable for inclusion (if patients are expected to be unable to adhere to treatment due to funding problems).  

研究实施时间:

Study execute time:

From2019-02-01To 2020-12-31 

干预措施:

Interventions:

组别:

连续病例

样本量:

26

Group:

Case Series

Sample size:

干预措施:

脐血移植

干预措施代码:

Intervention:

Umbilical cord blood stem cell transplantation

Intervention code:

研究实施地点:

Countries of recruitment and research settings:

国家:

中国 

省(直辖市):

安徽 

市(区县):

 

Country:

China 

Province:

Anhui 

City:

 

单位(医院):

中国科学技术大学附属第一医院 

单位级别:

三级甲等 

Institution
hospital:

The First Affiliated Hospital of USTC, Division of Life Sciences and Medcine, University of Science and Technology of China  

Level of the institution:

Tertiary A 

国家:

中国 

省(直辖市):

天津 

市(区县):

 

Country:

China 

Province:

Tianjin 

City:

 

单位(医院):

中国医学科学院血液病医院 

单位级别:

三级甲等 

Institution
hospital:

Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College  

Level of the institution:

Tertiary A 

测量指标:

Outcomes:

指标中文名:

1年总体生存率

指标类型:

主要指标 

Outcome:

1 year overall surviva

Type:

Primary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

中性粒细胞植入率

指标类型:

次要指标 

Outcome:

incidence of neutrophil engraftment

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

血小板植入率

指标类型:

次要指标 

Outcome:

incidence of platelet engraftment

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

急性移植物抗宿主病发生率

指标类型:

次要指标 

Outcome:

incidences of acute graft-vs-host-disease (aGVHD)

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

慢性移植物抗宿主病发生率

指标类型:

次要指标 

Outcome:

incidences of chronic graft-vs-host-disease (cGVHD)

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

免疫重建

指标类型:

次要指标 

Outcome:

immune reconstitution

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

感染发生率

指标类型:

次要指标 

Outcome:

incidences of infection

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

1年复发率

指标类型:

次要指标 

Outcome:

1 year incidence of relapse

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

健康生活质量

指标类型:

次要指标 

Outcome:

Health Related Quality of Life (HR-QoL)

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

180天移植相关死亡率

指标类型:

次要指标 

Outcome:

180 days transplantation related mortality

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

1年无GVHD无复发生存率

指标类型:

次要指标 

Outcome:

1 year GVHD-free, relapse-free survival (GRFS)

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

1年无病生存率

指标类型:

主要指标 

Outcome:

1 year disease-free survival (DFS)

Type:

Primary 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:

标本中文名:

骨髓

组织:

Sample Name:

bone marrow

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:

正在进行

Recruiting

年龄范围:

Participant age:

最小 Min age 1 years
最大 Max age 50 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):

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

N/A

UTN(全球唯一识别码):

盲法:

N/A

Blinding:

N/A

试验完成后的统计结果:

Calculated Results ater
the Study Completed:

研究负责(组长)单位:

Organizer institution (leader institution):

资料收集汇总单位:

6M

Data collection Institution:

资料管理单位:

临床试验公共管理平台:http://www.medresman.org

Data management Institution:

ResMan:http://www.medresman.org

资料分析单位:

病例记录表和电子采集和管理系统

Data analysis Institution:

Case Record Form(CRF) and Electronic Data Capture(EDC)

注册人:

Name on Registration:

 2019-01-26