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An open-label, single-center and single-arm clinical study of infusion of anti-BCMA CAR-T cells for patients with relapsed or refractory plasma cell malignancies
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注册号:

Registration number:

ChiCTR1800018137 

最近更新日期:

Date of Last Refreshed on:

2018-09-01 

注册时间:

Date of Registration:

2018-08-31 

注册号状态:

预注册  

Registration Status:

Prospective registration  

注册题目:

一项评价输注抗 BCMA CAR-T 治疗复发/难治浆细胞肿瘤的安全性和有效性的单中心、开放、单臂临床研究 

Public title:

An open-label, single-center and single-arm clinical study of infusion of anti-BCMA CAR-T cells for patients with relapsed or refractory plasma cell malignancies  

注册题目简写:

 

English Acronym:

 

研究课题的正式科学名称:

一项评价输注抗 BCMA CAR-T 治疗复发/难治浆细胞肿瘤的安全性和有效性的单中心、开放、单臂临床研究 

Scientific title:

An open-label, single-center and single-arm clinical study of infusion of anti-BCMA CAR-T cells for patients with relapsed or refractory plasma cell malignancies  

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:

王娜 

研究负责人:

周剑峰 

Applicant:

Na Wang 

Study leader:

Jianfeng Zhou 

申请注册联系人电话:

Applicant telephone:

+86 027-83663609 

研究负责人电话:

Study leader's telephone:

+86 027-83663609 

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:

wangna.2001@163.com 

研究负责人电子邮件:

Study leader's E-mail:

zhougene@medmail.com.cn 

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:

武汉市硚口区解放大道1095号 华中科技大学同济医学院附属同济医院  

研究负责人通讯地址:

武汉市硚口区解放大道1095号 华中科技大学同济医学院附属同济医院  

Applicant address:

1095 Jiefang Avenue, Qiaokou District, Wuhan, Hubei, China  

Study leader's address:

1095 Jiefang Avenue, Qiaokou District, Wuhan, Hubei, China  

申请注册联系人邮政编码:

Applicant postcode:

430030 

研究负责人邮政编码:

Study leader's postcode:

430030 

申请人所在单位:

华中科技大学同济医学院附属同济医院 

Applicant's institution:

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology  

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:

TJ-IRB20180814 

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:

华中科技大学同济医学院附属同济医院医学伦理委员会  

Name of the ethic committee:

Medical ethics committee of Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology  

伦理委员会批准日期:

Date of approved by ethic committee:

2018-08-30 

伦理委员会联系人:

王伟 

Contact Name of the ethic committee:

Wei Wang 

伦理委员会联系地址:

武汉市硚口区解放大道1095号 华中科技大学同济医学院附属同济医院  

Contact Address of the ethic committee:

1095 Jiefang Avenue, Qiaokou District, Wuhan, Hubei, China  

伦理委员会联系人电话:

Contact phone of the ethic committee:

 

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:

华中科技大学同济医学院附属同济医院 

Primary sponsor:

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology  

研究实施负责(组长)单位地址:

湖北武汉市硚口区解放大道1095号 

Primary sponsor's address:

1095 Jiefang Avenue, Qiaokou District, Wuhan, Hubei, 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):

湖北

市(区县):

Country:

China

Province:

hubei

City:

单位(医院):

华中科技大学同济医学院附属同济医院

具体地址:

武汉市硚口区解放大道1095号

Institution
hospital:

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Address:

1095 Jiefang Avenue, Hankou, Wuhan, Hubei, China

经费或物资来源:

南京驯鹿医疗技术有限公司 

Source(s) of funding:

Nanjing Iaso Biotherapeutics Co., Ltd. 

研究疾病:

浆细胞肿瘤 

Target disease:

plasma cell malignancies  

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:

探索性研究/预试验 

Study phase:

研究目的:

评价序贯输注抗BCMA CAR-T治疗复发/难治浆细胞肿瘤的安全性  

Objectives of Study:

to evaluate the security of anti-BCMA CAR-T therapy for relapsed/ refractory plasma cell malignancies  

药物成份或治疗方案详述:

 

Description for medicine or protocol of treatment in detail:

 

研究设计:

单臂 

Study design:

Single arm 

纳入标准:

1)年龄和性别:18 周岁≤年龄≤ 70 周岁,性别不限,自愿签署知情同意书; 2)第一阶段:根据 WHO 分类定义的浆细胞肿瘤1,经过至少三线治疗(包含硼替唑米和/或来那度胺为基础的化疗方案)后无效或复发的多发性骨髓瘤、浆细胞白血病、POEMS 综合征、意义未明的单克隆免疫球蛋白血症、原发性巨球蛋白血症或原发性淀粉样变。 第二阶段:经过至少三线治疗无效或复发的上述浆细胞肿瘤患者。 3)患者克隆性浆细胞膜表面 BCMA 表达为阳性。 4)患者无法接受自体造血干细胞移植治疗,或经自体造血干细胞移植后复发;研究者判定需要治疗。 5)ECOG 评分为 0 或 1 分(ECOG 评分标准见附录 4); 6)预期生存时间 ≥ 12 周; 7)受试者必须有适当的器官功能,入组前符合下列所有实验室检查结果: a)血常规:中性粒细胞 ≥ 1.0x109 /L;血红蛋白 ≥ 70 g/L;若有骨髓入侵,血小板 ≥ 50 x 109/L;若无骨髓入侵, 血小板≥ 70 x 109 /L。 b)肝功能:ALT 和 AST ≤ 2.5 × ULN;血清胆红素 ≤ 1.5 × ULN; c)肾功能:血清肌酸酐≤2.5 × ULN ;或根据 Cockcroft-Gault 公式计算的肌酐清除率 CrCl)≥ 60ml/min。 CrCl (ml/min)=([140 - 年龄 (岁)]×体重 (kg))/(72×血清肌酐 (mg/ dL)){×0.85 女性患者} d)电解质:血钾 ≥ 3.0 mmol/L;血钙 ≥ 2.0 mmol/L; 血镁≥ 0.5 mmol/L; e)凝血功能:纤维蛋白原≥1.0g/L;活化的部分凝血活酶时间(APTT)≦ULN+10s;凝血酶原时间(PT)≦ULN+3s; 8)受试者须愿意提供治疗前已有的有效诊断证据或接受骨髓检查,和在治疗后接受骨髓或有效检查; 9)育龄期女性和有生育能力男性受试者,在整个研究过程中和中断治疗 90 天内必须采取下列措施之一有效避孕:禁欲、双重屏障式避孕方法、宫内节育器,激素避孕药物使用至少在入组第一次用药前 3 个月开始使用。 10)男性受试者从开始治疗至停止治疗 90 天后禁止捐精。 11)签署知情同意书 12)受试者必须在试验前对本试验知情同意,并由本人(或其法定代理人)自愿签署了书面的知情同意书; 13)受试者或其法定代理人能够与研究者进行良好的沟通并能够依照方案规定完成试验。 

Inclusion criteria

1. to be aged 18 to 70 years, male and femaleVoluntary participation in the clinical trials and sign the informed consent; 2. types of plasm cell tumors included: Multiple myeloma; Amyloidosis; POEMS syndrome; MGUS that needs treatment; 3. Patients with BCMA+ tumor; 4. patients who are with relapsed disease after chemotherapy or hematopoietic stem cell transplantation (HSC); or patients are voluntary to accept anti-BCMA CAR-T cell therapy as the first-line therapy; 5. ECOG score 0 or 1; 6. Estimated survival of >=12 weeks; 7. Multiple organ function assessment: 1) Blood routine: N ≥ 1.0x109 /LHb ≥ 70 g/L plt ≥ 50 x 109/L(when BM positive) PLT≥ 70 x 109 /L(when BM negative). 2) Aspartate transaminase-alanine transaminase ratio < 2.5x ULN; Bilirubin < 1.5x ULN; 3) Creatinine < < 2.5x ULN; 4) K+ ≥ 3.0 mmol/LCa ≥ 2.0 mmol/L Mg≥ 0.5 mmol/L; 5) Fbg≥1.0g/L APTT≦ULN+10s PT≦ULN+3s; 8. providing valid diagnostic documents or bone marrow examination before treatment, and to receive bone marrow or effective examination after treatment; 9. Women of childbearing age and men with reproductive abilities were required to use one of the following effective contraception measures throughout the study and within 90 days of interruption of treatment: abstinence, double barrier contraceptive methods, intrauterine devices, The use of hormonal contraceptives began at least three months before the first dose; 10. Male subjects were not allowed to donate sperm from the beginning of treatment until 90 days after the treatment was stopped; 11. Voluntary participation in the clinical trials and sign the informed consent. 

排除标准:

1) 既往治疗史 a) 开始给药前 2 个月内接受过造血干细胞移植,或者筛选期内在造血干细胞移植后因移植物抗宿主病而接受免疫抑制治疗; b) 开始给药前 4 周内,接受过化疗、免疫治疗、放疗、大手术治疗的患者; c) 开始给药前 4 周内接受活疫苗和/或计划参加试验后接受活疫苗者; d) 开始给药前 4 周内接受过临床试验药物治疗,或正参加其它临床试验者; 2) 疾病史及手术史 a) 有浆细胞肿瘤中枢神经系统侵犯的患者; b) 高血压且药物治疗无法获得良好控制者(血压 > 140/90 mmHg); c) 多普勒超声评估:左心室射血分数(LVEF)< 50%; d) NCI CTCAE 5.0 分级 ≥ 2 级的心律失常,或男性 QTc > 450 ms、女性 QTc > 470 ms e) (QTc 采用 Fridericia 校正公式 QTc = QT/RR0.33 计算)者;有尖端扭转病史或先天性 QT 延长综合征史的患者; f) 给药前 12 个月内患有以下任意以一种疾病者:心肌梗死、严重或不稳定心绞痛、 g) 冠状动脉搭桥或外周动脉搭桥植入手术者、充血性心力衰竭、脑血管事件(包括短暂性脑缺血发作)等; h) 开始给药前 3 天内有发热或因感染进行了静脉滴注抗微生物治疗的(如静脉滴注抗菌药物、抗病毒药物、抗真菌药物),或筛选期时研究者判断有不能控制的、活动性感染疾病; i) 感染人免疫缺陷病毒(HIV)者; j) 乙肝表面抗原( HBsAg )检测阳性,且处于乙肝活动期( 乙肝核酸定量≥1.00×103 拷贝/ml)的患者; k) 丙肝抗体( Anti-HCV )检测阳性,且处于丙肝活动期 ( 丙肝核酸定量≥1.00×102 拷贝/ml)的患者的患者; l) 研究者判断有严重电解质紊乱患者; m) 具有明确的胃肠道出血倾向的患者,包括如下情况:有局部活动性溃疡病灶,且大便潜血(≧++);2 个月内有黑便、呕血病史者;研究者认为可能发生消化道大出血者; n) 有实体器官移植病史者; o) 研究者或申办者认为患有其它急性严重或慢性医学或心理疾病、不适合参加临床试验者; p) 妊娠期或哺乳期的女性或有生育计划的女性及男性。注:对于女性受试者,应为手术绝育、绝经后的患者,或者同意在研究治疗期间和研究治疗期结束后 6 个月内采取一种经医学认可的避孕措施【如宫内节育器(IUD),避孕套】;育龄女性受试者筛选期的血清或尿妊娠试验必须为阴性,且必须为非哺乳期;男性受试者,应为手术绝育,或同意在研究治疗期间和研究治疗期结束后 6 个月内采用一种经医学认可的避孕措施的患者。 

Exclusion criteria:

1. Past treatment history: 1) undergone HSCT or immunosuppressive treatment following HCST within 2 months; 2) undergone chemotherapy, immunotherapy, radiotherapy or major surgery within four weeks; 3) undergone Live vaccines within four weeks; 4) undergone clinical trials or are participating in other clinical trials within 4 weeks; 2. Medical History and Operation History: 1) Patients with plasma cell tumors with central nervous system invasion; 2) Hypertension and drug treatment can not obtain good control(blood pressure & GT; 140/90 mmHg); 3) Doppler ultrasound evaluation: LVEF< 50%; 4) NCI CTCAE 5.0 ≥ 2or 男性 QTc > 450 ms(male)女性 QTc > 470 ms(female); 5) Patients with advanced history of torsion or congenital QT prolongation of comprehensive history; 6) Patients with any of the following diseases within 12 months before administration: myocardial infarction, severe or unstable angina pectoris; 7) Coronary artery bypass or peripheral artery bypass graft implantation, congestive heart failure, cerebrovascular events(including transient cerebral ischemia), etc; 8) Within 3 days before the start of the drug administration, there was fever or intravenous infusion of anti-microbial treatment due to infection(such as intravenous infusion of antibacterial drugs, antiviral drugs, antifungal drugs), or during the screening period, the researcher judged that there was an uncontrollable, active infection. disease; 9) HIV+; 10) HBsAg+HBV DNA≥1.00×10^3 copies/ml; 11) Anti-HCV+;HCV -RNA≥1.00×10^2 copies/ml; 12) severe electrolyte disorders; 13) Patients with a clear tendency to gastrointestinal bleeding include the following: there is a localized active ulcer lesion, and latent blood in the stool(+ +); 2 months in the history of black stool, vomiting blood; The researchers believe there may be a major gastrointestinal hemorrhage; 14) People with a history of organ transplants; 15) unfit for clinical trials because of other acute severe or chronic medical or psychological conditions; 16) Pregnancy and nursing females ; Or females &males with fertility plans1. 

研究实施时间:

Study execute time:

From2018-08-30To 2019-08-31 

干预措施:

Interventions:

组别:

治疗组

样本量:

20

Group:

Case series

Sample size:

干预措施:

CAR-T细胞免疫治疗

干预措施代码:

Intervention:

Chimeric Antigen Receptor T-Cell Immunotherapy

Intervention code:

研究实施地点:

Countries of recruitment and research settings:

国家:

中国 

省(直辖市):

湖北 

市(区县):

 

Country:

China 

Province:

Hubei 

City:

 

单位(医院):

华中科技大学同济医学院附属同济医院 

单位级别:

三甲 

Institution
hospital:

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology  

Level of the institution:

Tertiary A hospital 

测量指标:

Outcomes:

指标中文名:

安全性

指标类型:

主要指标 

Outcome:

Safety

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:

外周血

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 18 years
最大 Max age 70 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):

非随机

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

Non-randomized

盲法:

N/A

Blinding:

N/A

试验完成后的统计结果(上传文件):

Calculated Results ater
the Study Completed(upload file):

原始数据公开时间:

The time of sharing IPD:

Real time access

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):

试验完成后12个月内公开,采用临床试验公共管理平台ResMan向公众开放查询

The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url):

The data will be published in the public management platform of clinical trials ResMan after the Study Completed 12 mouths

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:

设计有临床专用CRF表,专人进行纸质记录,并录入数据库,保存于研究者处;患者临床病史记录为纸质版,主管医师签字后保存于长征医院病案室,以备查阅。

Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture:

Each patient are required to fill one CRF table, All the CRF tables saved by researchers and will be saved by data base. The medical records with the signature of the doctor in charge are all in print edition, which will be saved in the medical-record department of Wuhan Tongji hospital.

数据管理委员会:

Data Managemen Committee:

有/Yes

注册人:

Name of Registration:

 2018-08-31
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