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CART细胞治疗晚期GUCY2C阳性消化系统肿瘤的安全性和有效性临床研究
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注册号:

Registration number:

ChiCTR2100053828 

最近更新日期:

Date of Last Refreshed on:

2021-11-30 

注册时间:

Date of Registration:

2021-11-30 

注册号状态:

预注册  

Registration Status:

Prospective registration  

注册题目:

CART细胞治疗晚期GUCY2C阳性消化系统肿瘤的安全性和有效性临床研究 

Public title:

Clinical study on the safety and effectiveness of CAR-T cells in the treatment of advanced GUCY2C-positive digestive system tumors 

注册题目简写:

 

English Acronym:

 

研究课题的正式科学名称:

CART细胞治疗晚期GUCY2C阳性消化系统肿瘤的安全性和有效性临床研究  

Scientific title:

Clinical study on the safety and effectiveness of CAR-T cells in the treatment of advanced GUCY2C-positive digestive system tumors 

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:

陈耐飞 

研究负责人:

崔久嵬 

Applicant:

Naifei Chen 

Study leader:

Jiuwei Cui 

申请注册联系人电话:

Applicant telephone:

0431-88783172 

研究负责人电话:

Study leader's telephone:

0431-88783172 

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:

chennaifei@163.com 

研究负责人电子邮件:

Study leader's E-mail:

cuijw@jlu.edu.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:

吉林省长春市朝阳区新民大街1号吉林大学第一医院7号楼3楼 

研究负责人通讯地址:

吉林省长春市朝阳区新民大街1号吉林大学第一医院7号楼3楼 

Applicant address:

3rd Floor, Building 7, Jilin University First Hospital, No. 1 Xinmin Street, Chaoyang District, Changchun City, Jilin Province, China 

Study leader's address:

Jinhai Road,Shanghai,China 

申请注册联系人邮政编码:

Applicant postcode:

Shanghai 

研究负责人邮政编码:

Study leader's postcode:

Shanghai 

申请人所在单位:

吉林大学白求恩第一医院 

Applicant's institution:

The First Bethune Hospital of Jilin 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:

210714-02 

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:

吉林大学第一医院干细胞伦理委员会 

Name of the ethic committee:

Stem Cell Ethics Committee of the First Hospital of Jilin University 

伦理委员会批准日期:

Date of approved by ethic committee:

2021-09-15 

伦理委员会联系人:

牛俊奇 

Contact Name of the ethic committee:

Niu Junqi 

伦理委员会联系地址:

吉林省长春市朝阳区新民大街1号 

Contact Address of the ethic committee:

No. 1 Xinmin Street, Changchun City, Jilin Province, China 

伦理委员会联系人电话:

Contact phone of the ethic committee:

0413-88782013 

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:

吉林大学白求恩第一医院 

Primary sponsor:

The First Bethune Hospital of Jilin University 

研究实施负责(组长)单位地址:

吉林省长春市朝阳区新民大街1号 

Primary sponsor's address:

No. 1 Xinmin Street, Changchun City, Jilin Province, 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):

吉林

市(区县):

长春

Country:

China

Province:

Jilin

City:

Changchun

单位(医院):

吉林大学白求恩第一医院

具体地址:

吉林省长春市朝阳区新民大街1号

Institution
hospital:

The First Bethune Hospital of Jilin University

Address:

No. 1 Xinmin Street, Changchun City, Jilin Province, 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:

结直肠癌、胃癌、肝癌、胰腺癌、食管腺癌、食管胃交界癌等 

Target disease:

Colorectal cancer, stomach cancer, liver cancer, pancreatic cancer, esophageal adenocarcinoma, esophageal gastric junction cancer, etc. 

研究疾病代码:

 

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:

研究目的:

研究的目的是通过晚期消化道肿瘤受试者的安全性和耐受性以及其他疗效终点,客观缓解率。  

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:

 

研究设计:

单臂 

Study design:

Single arm 

纳入标准:

1. 年龄18-65岁之间; 2. 在经合作方认可的实验室的免疫组化(IHC)测定靶点表达阳性; 3. 病理学证实消化道肿瘤; 4. 至少经过一、二线标准治疗无效或复发的患者,对于标准化治疗不耐受或自愿放弃的患者; 5. 按 RECIST1.1或EORTC或PERCIST标准至少具有一个颅外可测量病灶; 6. 预计生存期≥90天; 7. 主要器官功能正常,即符合下列标准: 1) ECOG体能状态评分为0~1或者KPS分数>70; 2) 血常规检查标准符合:HB≥90g/L (14天内未输血),ANC≥ 1.5 x 10^9/L,PLT≥80 x 10^9/L,Alb ≥ 2.8g/dL,serum lipase and amylase < 1.5×ULN(正常值上限); 3) 生化检查需符合以下标准:TBIL≤1.5 x ULN(正常值上限);ALT和AST≤2.5 x ULN;如有肝转移,则ALT和AST≤5xULN;血清Cr≤1xULN,内生肌酐清除率>50 ml/min (Cockcroft-Gault公式); 4) 心脏射血分数>55%; 8. 没有出血性疾病或凝血功能障碍; 9. 对显影剂不产生过敏; 10. 育龄妇女必须在入组前7天内进行妊娠实验(血清或尿液),且结果为阴性,并且愿意在实验期间和末次给予CART后8周采用适当的方法避孕(接受了绝育术或绝经后至少2年的女性可认定为不具有生育能力); 11. 受试者自愿加入本研究,签署知情同意书,依从性好,配合随访。  

Inclusion criteria

1. Aged 18 - 65 years; 2. Target expression >=1 + as determined by immunohistochemistry (IHC) in a laboratory accredited by the sponsor; 3. Pathological diagnosis is Digestive tract tumors; 4. Patients who are unable or unsuitable for surgery or who have recurrence after surgery; 5. According to RECIST 1.1 version or EORTC or PERCIST of the standard has at least one measles extracranial measurable lesion has not received radiotherapy; 6. Expected survival of >= 90 days; 7. 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 >= 1.5x10^9/L; PLT >= 80 x 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 <= 5 x ULN if liver metastases; serum Cr <= 1xULN, endogenous creatinine clearance > 50 ml / min (Cockcroft-Gault formula); 8. There was no hemorrhagic disease or coagulation dysfunction; 9. No allergy to the contrast agent; 10. 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); 11. Participants voluntarily joined the study, signed informed consent, compliance is good, with follow-up.  

排除标准:

1.既往有其他恶性肿瘤病史; 2.T细胞转导效率<5%或者培养后T细胞扩增小于2倍; 3.研究开始前4周内参加过其他药物临床试验; 4.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,具体情况由研究者评判),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)或心功能不全; 5.长期未愈合的胸部或其他部位的伤口或骨折; 6.具有精神类药物滥用史且无法戒除者或有精神障碍史者; 7.既往和目前有肺纤维化史、间质性肺炎、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; 8.存在不可控制或需要抗生素治疗的真菌、细菌、病毒或其他感染。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; 9.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; 10.已知存在HIV病史,或乙型肝炎(HBsAg阳性)或丙型肝炎病毒(抗HCV阳性)核酸检测阳性; 11.存在任何留置导管或引流管(如,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; 12.有脑转移的情况; 13.存在CNS病史或疾病,如癫痫发作疾病、脑缺血/出血、痴呆、小脑疾病,或任何涉及CNS的自身免疫性疾病; 14.存在重大免疫缺陷; 15.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; 16.入组前6个月内存在深静脉血栓或肺栓塞病史; 17. 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; 18.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。 

Exclusion criteria:

1.Previous history of other malignant tumors;2.T cell transduction efficiency <5% or T cell expansion less than 2 times after culture; 3. Participated in other drug clinical trials within 4 weeks before the start of the study; 4. 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; 5. Long-term unhealed chest or other parts of the wound or fracture; 6. Those with a history of abuse of psychotropic substances who can not be abstinent or who have mental disorders; 7. 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; 8. 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; 9. For subjects with previously used chemotherapy, >= 2 hematologic toxicity or >= 3 non-hematologic toxicity at enrollment according to NCI-CTCAE 4.0 criteria; 10. Known history of HIV or Hepatitis B (HBsAg positive) or Hepatitis C virus (anti-HCV positive) infection is known; 11. 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; 12. Brain metastases; 13. There is a CNS history or disease, such as seizure disease, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease involving CNS; 14. There is a significant immunodeficiency; 15. 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 16. There was a history of deep venous thrombosis or pulmonary embolism within the first 6 months of enrollment; 17. 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; 18. With hemorrhagic disease or coagulation dysfunction.  

研究实施时间:

Study execute time:

From2021-08-23To 2026-07-15 

征募观察对象时间:

Recruiting time:

From2021-11-15To 2026-07-15 

干预措施:

Interventions:

组别:

试验组

样本量:

12

Group:

experimental group

Sample size:

干预措施:

CAR-T 细胞

干预措施代码:

Intervention:

CAR-T Cell

Intervention code:

研究实施地点:

Countries of recruitment and research settings:

国家:

中国 

省(直辖市):

吉林 

市(区县):

长春 

Country:

China 

Province:

Jilin 

City:

Changchun 

单位(医院):

吉林大学白求恩第一医院 

单位级别:

三甲 

Institution
hospital:

The First Bethune Hospital of Jilin University  

Level of the institution:

Tertiary A 

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:

按方案进行

测量方法:

PET/CT

Measure time point of outcome:

Follow the scheme

Measure method:

PET/CT

指标中文名:

RECIST1.1

指标类型:

次要指标 

Outcome:

RECIST1.1

Type:

Secondary indicator 

测量时间点:

客观缓解率评估

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:

正在进行

Recruiting

年龄范围:

Participant age:

最小 Min age 18 years
最大 Max age 65 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):

未使用

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

Not used

盲法:

Blinding:

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

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

www.ictbio.com

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:

CRF

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

CRF

数据与安全监察委员会:

Data and Safety Monitoring Committee:

无/No

注册人:

Name of Registration:

 2021-11-30
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