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MUC-1 CART 细胞治疗晚期肺癌的安全性和有效性 临床研究

  • 发布时间:2018-03-25
  • 浏 览:129次

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注册号:

Registration number:

ChiCTR1800014954 

最近更新日期:

Date of Last Refreshed on:

2018-02-24 

注册时间:

Date of Registration:

2018-02-25 

注册号状态:

预注册  

Registration Status:

Prospective registration  

注册题目:

MUC-1 CART 细胞治疗晚期肺癌的安全性和有效性 临床研究 

Public title:

Safety and efficacy of MUC-1 CART cells in the treatment of advanced lung cancer Clinical research 

注册题目简写:

 

English Acronym:

 

研究课题的正式科学名称:

MUC-1 CART 细胞治疗晚期肺癌的安全性和有效性 临床研究 

Scientific title:

Safety and efficacy of MUC-1 CART cells in the treatment of advanced lung cancer Clinical research 

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:

李文静 

研究负责人:

高全立 

Applicant:

Wenjing Li 

Study leader:

Quanli Gao 

申请注册联系人电话:

Applicant telephone:

+86 15221087379 

研究负责人电话:

Study leader's telephone:

+86 15221087379 

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:

liwenjing@sidansai.com 

研究负责人电子邮件:

Study leader's E-mail:

wenjinghaoyun2008@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:

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:

中国河南郑州市金水区东明路127号 

Applicant address:

Room 201, Building 4, 998 Halei Road, Pudong New District, Shanghai, China  

Study leader's address:

127 Dongming Road, Jinshui District, Zhengzhou, He'nan, 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.  

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:

2017312 

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:

河南省肿瘤医院医学伦理委员会 

Name of the ethic committee:

He'nan Provincial Tumor Hospital Medical Ethics Committee 

伦理委员会批准日期:

Date of approved by ethic committee:

 

伦理委员会联系人:

宋永平 

Contact Name of the ethic committee:

Yongping Song 

伦理委员会联系地址:

河南省郑州市纬五路2号319 

Contact Address of the ethic committee:

Room 319, 2 Weiwu Road, Zhengzhou, He'nan, 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:

河南省肿瘤医院 

Primary sponsor:

Henan Province Cancer Hospital 

研究实施负责(组长)单位地址:

郑州市金水区东明路127号 

Primary sponsor's address:

127 Dongming Road, Jinshui District, Zhengzhou, He'nan, 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):

上海市

市(区县):

 

Country:

China

Province:

Shanghai

City:

 

单位(医院):

上海斯丹赛生物技术有限公司

具体地址:

中国(上海)静安区南京西路1038号梅龙镇广场3001室

Institution
hospital:

Innovative Cellular Therapeutics Co.,Ltd.

Address:

Room 3001, 1038 Nanjing Rd. (W), Jing'an District, Shanghai, China

经费或物资来源:

自筹 

Source(s) of funding:

Self-raised 

研究疾病:

转移性肺癌 

Target disease:

Metastatic 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:

I (Phase I study) 

研究目的:

研究的主要目的是评价 MUC-1 CART 靶向治疗肺癌的有效性。 次要目的包括评价 MUC-1 CART 靶向治疗肺癌的安全性、耐受性。 

Objectives of Study:

The primary objective of the study was to evaluate the effectiveness of MUC-1 CART targeted therapies for lung cancer; Secondary aims include evaluating the safety and tolerability of MUC-1 CART targeted therapies in lung cancer. 

药物成份或治疗方案详述:

 

Description for medicine or protocol of treatment in detail:

 

研究设计:

连续病例 

Study design:

Case series 

纳入标准:

1. 年龄18-65岁之间; 2. 在经申办方认可的实验室的免疫组化(IHC)测定ST糖基化MUC-1表达≥1+; 3. 病理学证实肺癌; 4. 至少接受过一次标准治疗后或者经过一线、二线治疗失败,再次出现难治性、复发性肺癌,无法进行手术或者不适合手术的患者,并且没有肝、淋巴结转移; 5. 诊断为非小细胞肺癌的患者必须检测EGFR突变情况、ALK易位情况,如果有前面提到的情况需要接受适当的酪氨酸酶抑制剂治疗后无效的患者; 6. 接受治疗前4周并未进行中药治疗; 7. 血清中钙、钾、镁的水平在标准范围内; 8. 按RECIST 1.1版标准至少具有一个颅外可测量病灶,可测量病灶未接受过放疗; 9. 研究开始前4周内未接受过化疗、放疗、分子靴向治疗以及手术,并己从之前治疗的急性毒性反应中恢复,脱发以及外周神经毒性除外; 10. 预计生存期≥3个月; 11. 无症状的脑转移,或者在研究开始前经过局部治疗(手术/放疗)的脑转移,临床症状稳定至少8周; 12. 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>60; 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,lymphocyte (LY) ≥ 0.7×10^9/L, LY% ≥ 15%, 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%; 13. 没有出血性疾病或凝血功能障碍; 14. 对显影剂不产生过敏; 15. 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); 16. 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. Between the ages of 18-65 years; 2. ST glycosylated MUC-1 expression> 1 + as determined by immunohistochemistry (IHC) in a laboratory accredited by the sponsor; Pathology confirmed lung cancer; 4. Have received at least one standard treatment or after first-line, second-line treatment fails, again appear refractory, recurrent lung cancer, surgery or not suitable for surgery in patients without liver and lymph node metastasis; 5. Patients diagnosed with non-small cell lung cancer must be tested for EGFR mutations and ALK translocations, if any of the previously mentioned conditions require treatment ineffective with appropriate tyrosinase inhibitors; 6. 4 weeks before treatment did not carry out traditional Chinese medicine treatment; 7. Serum calcium, potassium and magnesium levels in the standard range; 8. According to RECIST 1.1 version of the standard has at least one extracepular measurable lesions can be measured lesions have not received radiotherapy; 9. Chemotherapy, radiotherapy, molecular boot therapy and surgery were not received within 4 weeks prior to study start-up and have been rescued from acute toxic reactions previously treated except for hair loss and peripheral neurotoxicity; 10. Expected survival ≥ 3 months; 11. Asymptomatic brain metastases, or brain metastases that have undergone topical (surgery / radiotherapy) therapy prior to study initiation, are clinically stable for at least 8 weeks; 12. The main organs function properly, that is, meet the following criteria: 1) ECOG physical status score is 0 ~ 1 or KPS score> 60; 2) The blood test was consistent with the following criteria: HB≥90g/L (no blood transfusion within 14 days), ANC≥1.5×10^9/L, PLT≥80×10^9/L, lymphocyte/L, LY% ≥15%, Alb ≥2.8g/dL, serum lipase and amylase <1.5×ULN (upper limit of normal); 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); 4) Cardiac ejection fraction> 55%; 13. No hemorrhagic disease or coagulation disorders; 14. Does not cause allergic to the developer; 15. Women of childbearing age must undergo 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 (who have undergone sterilization or menopause Women who have been at least 2 years old can be considered as having no fertility); 16. Participants voluntarily joined the study, signed informed consent, compliance is good, with follow-up. 

排除标准:

1. T细胞转导效率<10%或者通过人工抗原呈递细胞(aAPC)刺激后T细胞扩增小于5倍; 2. 既往接受过MUC-1靶向治疗、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. 脑膜转移或症状无法控制的脑转移; 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. 入组的12个月内有心肌梗死、心脏血管成形术或支架植入术、不稳定型心绞痛或其他具有临床意义的心脏疾病病史、纽约心脏协会(NYHA)III类或IV类心力衰竭; 16. 存在重大免疫缺陷; 17. 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; 18. 入组6个月内存在深静脉血栓或肺栓塞病史; 19. 任何妊娠或正在哺乳中有生育能力的女性(接受了绝育术或绝经后至少2年的女性可认为不具有生育能力); 20. 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; 21. 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; 22. 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。 

Exclusion criteria:

1. T-cell transduction efficiency <10% or T-cell expansion less than 5-fold after stimulation with artificial antigen-presenting cells (aAPC) 2. Previously received MUC-1 targeted therapy, 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 metastasis or uncontrollable 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 was a history of myocardial infarction, angioplasty or stenting, unstable angina or other clinically significant heart disease within the 12-month period, New York Heart Association (NYHA) class III or IV heart failure ; 16. There is a significant immunodeficiency; 17. 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 for CRS during the pretreatment; 18. The group had a history of deep venous thrombosis or pulmonary embolism within 6 months; 19. Any woman who has fertility during pregnancy or who is breast-feeding (women who have undergone sterilization or who have been at least 2 years after menopause may not be considered fertile); 20. A history of autoimmune diseases (eg, Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus) that cause damage to the terminal organ or which require systemic immunosuppression / systemic disease modulation over the past two years; 21. Any disease that may interfere with the safety of the study treatment or assessment of efficacy; 22. Female subjects who are unwilling to take birth control 6 months after signing the consent form and from completing the CART administration. 

研究实施时间:

Study execute time:

From2017-12-01To 2018-11-30 

干预措施:

Interventions:

组别:

实验组

样本量:

10

Group:

Case series

Sample size:

干预措施:

MUC1 CART

干预措施代码:

 

Intervention:

MUC1 CART

Intervention code:

研究实施地点:

Countries of recruitment and research settings:

国家:

中国 

省(直辖市):

河南省 

市(区县):

 

Country:

China 

Province:

He'nan 

City:

 

单位(医院):

河南省肿瘤医院 

单位级别:

三甲 

Institution
hospital:

Henan Province Cancer Hospital  

Level of the institution:

Tertiary A Hospital 

测量指标:

Outcomes:

指标中文名:

petCT

指标类型:

主要指标 

Outcome:

petCT

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:

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):

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

no

盲法:

 

Blinding:

 

原始数据公开时间:

The time of sharing IPD:

即时公开/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):

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:

CRF及EDC

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

CRF and EDC

数据管理委员会:

Data Managemen Committee:

无/No

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