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：	ChiCTR1900022609
最近更新日期： Date of Last Refreshed on：	2019-04-18 10:34:22
注册时间： Date of Registration：	2019-04-18 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	（MUC-1+CD19） CART 细胞治疗晚期肺癌的安全性和有效性临床研究
Public title：	(MUC-1 + CD19) targeted Chimeric Antigen Receptor T Cells (CART) Therapy in lung cancer
注册题目简写：
English Acronym：
研究课题的正式科学名称：	（MUC-1+CD19） CART 细胞治疗晚期肺癌的安全性和有效性临床研究
Scientific title：	(MUC-1 + CD19) targeted Chimeric Antigen Receptor T Cells (CART) Therapy in lung cancer
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：	林敏	研究负责人：	庞鹏飞
Applicant：	Min Lin	Study leader：	Pengfei Pang
申请注册联系人电话： Applicant telephone：	+86 15618108082	研究负责人电话： Study leader's telephone：	+86 13300227597
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：	linmin@sidansai.com	研究负责人电子邮件： Study leader's E-mail：	linmin@sidansai.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：	上海市浦东新区张江高科哈雷路998号4号楼201	研究负责人通讯地址：	广东省珠海市香洲区梅华东路52号
Applicant address：	Room 201, 4th Building, 998 Halei Road, Zhangjing Hi-tech park, Shanghai, China	Study leader's address：	52 Meihua Road East, Xiangzhou District, Zhuhai, Guangdong, China
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：	上海斯丹赛生物技术有限公司
Applicant's institution：	Innovative Cellular Therapeutics Co.,Ltd.
研究负责人所在单位：	中山大学附属第五医院
Affiliation of the Leader：	The Fifth Hospital Affiliated to Zhongshan 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：	中大五院【2018】伦字第（K21-2）号	伦理委员会批件附件： Approved file of Ethical Committee：
批准本研究的伦理委员会名称：	中山大学附属第五医院医学伦理委员会
Name of the ethic committee：	The Fifth Hospital Affiliated to Zhongshan University Medical Science Research Ethics Committee
伦理委员会批准日期： Date of approved by ethic committee：	2018-10-09 00:00:00
伦理委员会联系人：
Contact Name of the ethic committee：
伦理委员会联系地址：
Contact Address of the ethic committee：
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：

中山大学附属第五医院

Primary sponsor：

The Fifth Hospital Affiliated to Zhongshan University

研究实施负责（组长）单位地址：

广东省珠海市香洲区梅华东路52号

Primary sponsor's address：

52 Meihua Road East, Xiangzhou District, Zhuhai, Guangdong, 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)：	广东省	市(区县)：	珠海市
Country：	China	Province：	Guangdong	City：	Zhuhai
单位(医院)：	中山大学附属第五医院	具体地址：	广东省珠海市香洲区梅华东路52号
Institution hospital：	The Fifth Hospital Affiliated to Zhongshan University	Address：	52 Meihua Road East, Xiangzhou District, Zhuhai, Guangdong, China

经费或物资来源：

上海斯丹赛生物技术有限公司

Source(s) of funding：

Innovative Cellular Therapeutics Co.,Ltd.

研究疾病：

晚期肺癌

Target disease：

lung cancer

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：

I期临床试验

Study phase：

1

研究设计：

单臂

Study design：

Single arm

研究目的：

研究的主要目的是通过晚期肺癌受试者的客观缓解率测定评价CART的疗效。次要目的包括评估CART的安全性和耐受性以及其他疗效终点。

Objectives of Study：

The primary objective of phase 1 is to evaluate the safety of CART regimens. The primary objective of phase 2 is to evaluate the efficacy of CART, as measured by objective response rate in subjects with colorectal cancer; Secondary objectives will include assessing the safety and tolerability of CART and additional efficacy endpoints.

药物成份或治疗方案详述：

Description for medicine or protocol of treatment in detail：

纳入标准：

Inclusion criteria

1. aged 18 - 65 years old;
2. Target expression ≥1 + as determined by immunohistochemistry (IHC) in a laboratory accredited by the sponsor;
3. Pathological diagnosis is lung cancer;
4. Patients with advanced non-small cell lung cancer who failed to receive standard first-line and second-line drugs
5. Patients diagnosed as non-small cell lung cancer must be tested for EGFR mutation and ALK translocation. If the aforementioned condition requires treatment with appropriate tyrosinase inhibitors, the patient will not respond
6. Four weeks before treatment, there was no treatment with traditional Chinese medicine;
7. Serum calcium, potassium and magnesium levels were within the standard range;
8. At least one extracranial measurable lesion according to RECIST 1.1 standard;
9. Chemotherapy, radiotherapy, molecular boot therapy and surgery were not performed in the first four weeks of the study and have recovered from the acute toxicity of previous treatments, with the exception of alopecia and peripheral neurotoxicity;
10. Expected survival of ≥ 3 months; 
11. The main organs function properly, that is, meet the following criteria:
1) The ECOG physical status score is 0-2;
2) Blood test should meet the following criteria: HB≥90g/L (no blood transfusion within 14 days); ANC≥1.5 ×10^9/L; PLT≥80 ×10^9/L;
3) biochemical tests should meet the following criteria: TBIL≤1.5 x ULN (upper limit of normal); ALT and AST≤2.5 x ULN; ALT and AST≤5xULN if liver metastases; serum Cr≤1xULN, endogenous creatinine clearance > 50 ml / min (Cockcroft-Gault formula);
12. Women of childbearing age must have a pregnancy test (serum or urine) within 7 days before enrollment and the result is negative and are willing to use appropriate methods of contraception either during the experiment and 8 weeks after the last dose of CART (subject to sterilization or menopause Women who have been at least 2 years old can be considered as having no fertility);
13. Participants voluntarily joined the study, signed informed consent, good compliance with follow-up.

排除标准：

1.T细胞转导效率<10%或者培养后T细胞扩增小于5倍；
2.嵌合抗原受体治疗或其他转基因T细胞治疗；
3.妊娠或哺乳期妇女；
4.研究开始前4周内参加过其他药物临床试验；
5.患有高血压且经单一降压药物无法获得良好控制者（收缩压 > 140 mmHg，舒张压>90 mmHg），患有I级以上心肌缺血或心肌梗塞、I级及以上心律失常（包括QT间期≥ 440ms）或心功能部全；
6.长期未愈合的胸部或其他部位的伤口或骨折；
7.具有精神类药物滥用史且无法戒除者或有精神障碍史者；
8.既往和目前有肺纤维化史、间质行肺炎、尘肺、放射性肺炎、药物相关肺炎、肺功能严重受损等的客观证据的患者；
9.存在不可控制或需要抗菌剂治疗的真菌、细菌、病毒或其他感染。如果对活性治疗有应答，在咨询医学监查员后，允许存在单纯的尿路感染和无并发症的细菌性咽炎；
10.对于既往使用过化疗的受试者，根据NCI-CTCAE 4.0标准，入组时存在≥2级血液学毒性，或≥3级非血液学毒性；
11.已知存在HIV或乙型肝炎（HBsAg阳性）或丙型肝炎病毒（抗HCV阳性）感染病史；
12.存在任何留置导管或引流管（如，经皮肾造口管、留置弗利氏导尿管、胆汁引流管或胸膜/腹膜/心包导管）。允许使用专用中心静脉导管；
13.有脑转移的情况；
14.存在CNS病史或疾病，如癫痫发作疾病、脑血管缺血/出血、痴呆、小脑疾病，或任何涉及CNS的自身免疫性疾病；
15.存在重大免疫缺陷；
16.对本研究中的主要治疗药物（包括预处理期间使用的氟达拉滨、环磷酰胺、美司钠以及防治CRS的托珠单抗及抗感染药物等）具有重度超敏反应病史；
17.入组前6个月内存在深静脉血栓或肺栓塞病史；
18.过去2年内存在导致末端器官损伤或需要全身免疫抑制/全身疾病调节药物的自身免疫性疾病（如，克罗恩氏病、类风湿性关节炎、系统性红斑狼疮）病史；
19.有任何可能对研究治疗的安全性或疗效评估产生干扰的疾病；
20.自签署同意书起至完成CART给药后6个月不愿意采取节育措施的女性受试者。
21.有出血性疾病或凝血功能障碍；
22.对显影剂产生过敏。

Exclusion criteria：

1. T cell transduction efficiency <10% or T cell expansion less than 5 times after culture;
2. Chimeric antigen receptor therapy or other transgenic T cell therapy;
3. Pregnant or lactating women;
4. Participate in other drug clinical trials within 4 weeks before the study begins;
5. Patients with hypertension who are not well controlled by a single antihypertensive medication (systolic> 140 mmHg, diastolic> 90 mmHg), patients with grade I or higher myocardial ischemia or myocardial infarction, grade I and above arrhythmias Including QT interval ≥ 440ms) or complete cardiac function;
6. Long-term unhealed chest or other parts of the wound or fracture;
7. Those with history of abuse of psychotropic substances who can not be abstinent or who have mental disorders;
8. Past and current patients with objective evidence of a history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-associated pneumonia, severely impaired pulmonary function;
9. There are fungi, bacteria, viruses or other infections that can not be controlled or require antimicrobial treatment. If there is a response to active therapy, a simple urinary tract infection and no complication of bacterial pharyngitis are allowed after consultation with the medical examiner;
10. For subjects with previously used chemotherapy, ≥2 hematologic toxicity or ≥3 non-hematologic toxicity at enrollment according to NCI-CTCAE 4.0 criteria;
11. A known history of HIV or Hepatitis B (HBsAg positive) or Hepatitis C virus (anti-HCV positive) infection is known;
12. There are any indwelling catheters or drains (eg, percutaneous nephrostomy tubes, indwelling Foley catheters, bile ducts, or pleural / peritoneal / pericardial catheters). Allow use of a dedicated central venous catheter;
13. brain metastases;
14. There is a CNS history or disease, such as seizure disease, cerebrovascular ischemia / hemorrhage, dementia, cerebellar disease, or any autoimmune disease involving CNS;
15. There is a significant immunodeficiency;
16. Have a history of severe hypersensitivity reactions to the major therapeutic agents used in this study, including fludarabine, cyclophosphamide, mesna, and tocilizumab and anti-infectives against CRS during pretreatment;
17. There was a history of deep venous thrombosis or pulmonary embolism within the first 6 months of enrollment;
18. A history of autoimmune diseases (eg, Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus) that cause damage to the terminal organ or that require systemic immunosuppression / systemic disease modulation over the past two years;
19. Any disease that may interfere with the safety of the study treatment or assessment of efficacy;
20. Female subjects who are unwilling to take birth control 6 months after signing CART since signing consent;
21. hemorrhagic disease or coagulation dysfunction;
22. allergy to photographic developer.

研究实施时间：

Study execute time：

从 From 2019-04-19 00:00:00至 To 2024-04-18 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2019-04-19 00:00:00 至 To 2024-04-18 00:00:00

干预措施：

Interventions：

组别：	Case series	样本量：	6
Group：	Case series	Sample size：	6
干预措施：	（MUC-1+CD19） CART 细胞治疗	干预措施代码：
Intervention：	(MUC-1+CD19) CART cell therapy	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	广东省	市(区县)：	珠海市
Country：	China	Province：	Guangdong Province	City：	Zhuhai
单位(医院)：	中山大学附属第五医院	单位级别：	三甲医院
Institution hospital：	The Fifth Hospital Affiliated to Zhongshan University	Level of the institution：	Tertiary A Hospital

测量指标：

Outcomes：

指标中文名：	PET CT	指标类型：	主要指标
Outcome：	PET CT	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：

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）：

N/A

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

N/A

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

不公开/Private

盲法：	N/A
Blinding：	N/A

是否共享原始数据： IPD sharing	是Yes
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）：	上海斯丹赛生物技术有限公司官网，www.ictbio.com,试验完成后6个月内
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	www.ictbio.com, Within six months after the trial complete
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：	EDC
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	EDC
数据与安全监察委员会： Data and Safety Monitoring Committee：	无/No
注册人： Name of Registration：	2019-04-18 10:34:22