中国临床试验注册中心 - 世界卫生组织国际临床试验注册平台一级注册机构

注册号： Registration number：	ChiCTR1800016315
最近更新日期： Date of Last Refreshed on：	2018-05-24 23:34:52
注册时间： Date of Registration：	2018-05-24 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	抗CD19嵌合抗原受体T淋巴细胞（CD19 CAR-T）治疗复发性或难治性B细胞恶性肿瘤的临床研究
Public title：	CD19-targeting CAR T Cells in Relapsed or Refractory B-cell Malignancies
注册题目简写：
English Acronym：
研究课题的正式科学名称：	抗CD19嵌合抗原受体T淋巴细胞（CD19 CAR-T）治疗复发性或难治性B细胞恶性肿瘤的临床研究
Scientific title：	CD19-targeting CAR T Cells in Relapsed or Refractory B-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：	葛健	研究负责人：	夏瑞祥
Applicant：	Ge Jian	Study leader：	Xia Ruixiang
申请注册联系人电话： Applicant telephone：	+86 0551 62923653	研究负责人电话： Study leader's telephone：	+86 0551 62923653
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：	gejian52@163.com	研究负责人电子邮件： Study leader's E-mail：	xrx2041@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：	安徽省合肥市蜀山区绩溪路218号	研究负责人通讯地址：	安徽省合肥市蜀山区绩溪路218号
Applicant address：	218 Jixi Road, Shushan District Hefei, Anhui, China	Study leader's address：	218 Jixi Road, Shushan District Hefei, Anhui, China
申请注册联系人邮政编码： Applicant postcode：	230022	研究负责人邮政编码： Study leader's postcode：
申请人所在单位：	安徽医科大学第一附属医院
Applicant's institution：	The First Affiliated Hospital of Anhui Medical University
研究负责人所在单位：	安徽医科大学第一附属医院
Affiliation of the Leader：	The First Affiliated Hospital of Anhui Medical University

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：	PJ2018-02-08(1)	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：	安徽医科大学第一附属医院临床医学研究伦理委员会
Name of the ethic committee：	The medical ethic committee of The First Affiliated Hospital of Anhui Medical University
伦理委员会批准日期： Date of approved by ethic committee：	2018-03-30 00:00:00
伦理委员会联系人：	王晓虎
Contact Name of the ethic committee：	Wang Xiaohu
伦理委员会联系地址：	安徽省合肥市蜀山区绩溪路218号
Contact Address of the ethic committee：	218 Jixi Road, Shushan District Hefei, Anhui, 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：

安徽医科大学第一附属医院

Primary sponsor：

The First Affiliated Hospital of Anhui Medical University

研究实施负责（组长）单位地址：

安徽省合肥市蜀山区绩溪路218号

Primary sponsor's address：

218 Jixi Road, Shushan 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)：	安徽省	市(区县)：	合肥市
Country：	China	Province：	Anhui	City：	Hefei
单位(医院)：	安徽医科大学第一附属医院	具体地址：	安徽省合肥市蜀山区绩溪路218号
Institution hospital：	The First Affiliated Hospital of Anhui Medical University	Address：	218 Jixi Road, Shushan District Hefei, Anhui, China

经费或物资来源：

亘喜生物科技（上海）有限公司

Source(s) of funding：

Gracell Biotechnology Ltd.

研究疾病：

B细胞恶性肿瘤

Target disease：

B cell malignancies

研究疾病代码：

Target disease code：

研究类型：

治疗研究

Study type：

Treatment study

研究所处阶段：

探索性研究/预试验

Study phase：

0

研究设计：

非随机对照试验

Study design：

Non randomized control

研究目的：

评估抗CD19嵌合抗原受体T细胞治疗复发性或难治性B细胞恶性肿瘤的安全性和有效性

Objectives of Study：

To evaluate the safety and efficacy of CD19-targetting CAR-T therapy in relapsed or refractory B cell malignancies

药物成份或治疗方案详述：

CD19 CAR-T细胞采用慢病毒载体转染表达抗CD19的scFv、CD3ζ和CD28共刺激域，通过静脉回输治疗。受试者将接受0.1-10×10^6 CAR+ T细胞，分为三次回输治疗：D0，D1和D2分别回输细胞总量的10%，30%和60%。

Description for medicine or protocol of treatment in detail：

CD19 CAR-T cells transduced with a lentiviral vector to express anti-CD19 scFv CD3z:CD28 administered by IV infusion. Subjects will receive 0.1-10 x 10^6 transduced CAR T cells as a split dose over three days as follows:Day 0, 10% fraction, Day 1, 30% fraction, Day 2, 60% fraction.

纳入标准：

Inclusion criteria

1. Relapsed or refractory B cell malignancies:
(1) Relapsed or refractory B ALL;
Relapse was defined as presence of > 5% blasts at screening, or second or subsequent bone marrow (BM) relapse, or any BM relapse after allogeneic SCT and must be ≥ 6 months from SCT at the time of CD19 CAR-T infusion. Refractory was defined by not achieving an initial CR after 2 cycles of a standard chemotherapy regimen (primary refractory). Patients who were refractory to subsequent chemotherapy regimens after an initial remission were considered chemorefractory;
(2) Patients with Ph+ ALL were eligible if they are intolerant to or have not achieved a remission after two lines of TKI (tyrosine kinase inhibitor) therapy, or if TKI therapy is contraindicated, or ineligible for allogeneic SCT because of: a.Comorbid disease; b. Other contraindications to allogeneic SCT conditioning regimen; c.Lack of suitable donor; d.Prior hematopoietic stem cell transplant (HSCT); e.Declined allogeneic HSCT as a therapeutic option
(3) Relapsed or refractory NHL:
1) Histopathological CD19+.
2) No response to last line of therapy i. PD as best response to most recent therapy regimen ii. SD as best response to most recent therapy with duration no longer than 6 month from last dose of therapy OR
Refractory post-ASCT i. Disease progression or relapsed less than or equal to 12 months of ASCT (must have biopsy proven recurrence in relapsed subjects) ii. If salvage therapy is given post-ASCT, the subject must have had no response to or relapsed after the last line of therapy;
3) Subjects must have received adequate prior therapy including at a minimum: anti-CD20 monoclonal antibody unless investigator determines that tumor is CD20-negative and an anthracycline containing chemotherapy regimen for subjects with transformed FL must have received prior chemotherapy for follicular lymphoma and subsequently have chemorefractory disease after transformation to DLBCL;
4) At least one measurable lesion per revised IWG Response Criteria;
2. Aged 18-75 years old;
3. Expected survival ≥ 12 weeks;
4. Adequate renal, hepatic, pulmonary and cardiac function defined as:
1) Creatinine clearance (as estimated by Cockcroft Gault) > 60 mL/min;
2) Serum ALT/AST <2.5 ULN;
3) Total bilirubin <1.5 mg/dl, except in subjects with Gilbert's syndrome;
4) Cardiac ejection fraction >50%, no evidence of pericardial effusion as determined by an ECHO, and no clinically significant pleural effusion;
5) Baseline oxygen saturation >92% on room air;
5. Eastern cooperative oncology group (ECOG) performance status of 0 - 2;
6. Pregnant or lactating women must have a negative pregnancy test before infusion, and agree to take effective contraception during the trial;
7. Apheresis product received and accepted;
8. Written informed consent.

排除标准：

1. 单独的髓外复发B-ALL；
2. 其他恶性肿瘤患者；
3. 合并遗传疾病，唐氏综合征除外；
4. 排除Burkitt’s淋巴瘤/白血病；
5. 之前接受过基因治疗产品，抗CD19/抗CD3治疗，或其他抗CD19疗法；
6. 活动性HBV、HCV或其他未控制的感染；
7. 2-4级GVHD；
8. 以下药物或治疗需排除：
1) CAR-T回输前72h内糖皮质激素，生理性替代疗法除外；
2) CAR-T回输前6周内异基因细胞疗法，例如供体淋巴细胞回输；
3) GVHD治疗；
4) 在预处理前因瘤负荷已清除而停止的化疗；
5) 中枢神经系统预防性治疗；
9. 活动性中枢神经系统疾病（CNS 2病变[CSF含有幼稚细胞，但＜5 WBCs/μl]患者可入选）；
10. 研究者认为可能增加受试者危险性或干扰试验结果的任何情况。

Exclusion criteria：

1. Isolated extra-medullary relapse leukemia;
2. Other malignancies;
3. Concomitant genetic syndrome, with the exception of Down Syndrome;
4. Burkitt's lymphoma/leukemia;
5. Treatment with any prior gene therapy product, anti-CD19/anti-CD3 therapy, or any other anti-CD19 therapy;
6. Active hepatitis B, C, or any uncontrolled infection;
7. Grade 2 to 4 Graft versus Host Disease (GVHD);
8. Medications or treatments that were to be excluded:
1) Corticosteroids within 72 hours of infusion, with the exception of physiologic replacement;
2) Allogeneic cellular therapy, such as donor lymphocyte infusion within 6 weeks prior to infusion;
3) GVHD therapies;
4) Chemotherapy stopped prior to lymphodepletion based on clearance;
5) CNS prophylaxis treatment;
9. Active central nervous system (CNS) disease (CNS 2 disease [CSF containing blasts, but < 5 WBCs/microliter] patients were eligible);
10. Any condition that investigator considered may increase the risk of the subjects or interfere with the trial results.

研究实施时间：

Study execute time：

从 From 2018-06-01 00:00:00至 To 2020-06-30 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2018-06-01 00:00:00 至 To 2019-12-31 00:00:00

干预措施：

Interventions：

组别：	Case series	样本量：	18
Group：	Case series	Sample size：	18
干预措施：	CD19 CAR-T	干预措施代码：
Intervention：	CD19 CAR-T	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	安徽省	市(区县)：	合肥市
Country：	China	Province：	Anhui	City：	Hefei
单位(医院)：	安徽医科大学第一附属医院	单位级别：	三甲
Institution hospital：	The First Affiliated Hospital of Anhui Medical University	Level of the institution：	Tertiary A Hospital

测量指标：

Outcomes：

指标中文名：	毒性与不良事件等级	指标类型：	主要指标
Outcome：	Grade of Toxicities and Adverse Events	Type：	Primary indicator
测量时间点：	4周/8周/12周	测量方法：	观察和检测
Measure time point of outcome：	4-week/8-week/12-week	Measure method：	observation and test

指标中文名：	总缓解率	指标类型：	次要指标
Outcome：	overall response rate	Type：	Secondary indicator
测量时间点：	4周/8周/12周	测量方法：	观察和测量
Measure time point of outcome：	4-week/8-week/12-week	Measure method：	observation and measure

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：	血液	组织：	肿瘤
Sample Name：	Blood	Tissue：	tumor
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	岁 years
最大 Max age	75	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）：

不适用

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

Not Available

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	否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）：	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 months
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：	设计临床试验专用CRF，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安徽医科大学第一附属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：	All the CRFs will be saved.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 The First Affiliated Hospital of Anhui Medical University.
数据与安全监察委员会： Data and Safety Monitoring Committee：	有/Yes
注册人： Name of Registration：	2018-05-24 23:34:52