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TriCAR-T-CD19细胞介导CD19+复发难治性非霍奇金淋巴瘤的过继免疫治疗

  • 发布时间:2018-02-02
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TriCAR-T-CD19细胞介导CD19+复发难治性非霍奇金淋巴瘤的过继免疫治疗...

注册号:

Registration number:

ChiCTR1800014528 

最近更新日期:

Date of Last Refreshed on:

2018-01-19 

注册时间:

Date of Registration:

2018-01-19 

注册号状态:

补注册  

Registration Status:

Retrospective registration  

注册题目:

TriCAR-T-CD19细胞介导CD19+复发难治性非霍奇金淋巴瘤的过继免疫治疗 

Public title:

TriCAR-T-CD19 Adoptive Immunotherapy for CD19-positive Refractory/Relapsed non-Hodgkin lymphoma 

注册题目简写:

 

English Acronym:

 

研究课题的正式科学名称:

TriCAR-T-CD19细胞介导CD19+复发难治性非霍奇金淋巴瘤的过继免疫治疗 

Scientific title:

TriCAR-T-CD19 Adoptive Immunotherapy for CD19-positive Refractory/Relapsed non-Hodgkin lymphoma 

研究课题代号(代码):

Study subject ID:

Trident-19 

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:

司远 

研究负责人:

周明 

Applicant:

Yuan Si 

Study leader:

Ming Zhou 

申请注册联系人电话:

Applicant telephone:

+86 15620708813 

研究负责人电话:

Study leader's telephone:

+86 13974996615 

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:

yuan.si@timmune.com 

研究负责人电子邮件:

Study leader's E-mail:

zhouming_0321@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:

天津市空港经济区环河北路76号空港商务园西区19号楼 

研究负责人通讯地址:

湖南省长沙市解放西路61号 湖南省人民医院第二住院楼10楼血液科 

Applicant address:

19th Building, Airport Economic Zone, 76 Huanhe Road North, Tianjin, China 

Study leader's address:

61 Jiefang Road West, Changsha, Hunan, China 

申请注册联系人邮政编码:

Applicant postcode:

300000 

研究负责人邮政编码:

Study leader's postcode:

 

申请人所在单位:

天津天锐生物科技有限公司 

Applicant's institution:

Timmune Biotech Inc. 

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:

2017-08 

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:

湖南省人民医院医学伦理委员会 

Name of the ethic committee:

Medical Ethics Committee of Hunan Provincial People's Hospital 

伦理委员会批准日期:

Date of approved by ethic committee:

2017-09-14 

伦理委员会联系人:

宁宁 

Contact Name of the ethic committee:

Ning Ning 

伦理委员会联系地址:

湖南省长沙市解放西路61号 

Contact Address of the ethic committee:

61 Jiefang Road West, Changsha, Hunan, China 

伦理委员会联系人电话:

Contact phone of the ethic committee:

+86 0731-83929085 

伦理委员会联系人邮箱:

Contact email of the ethic committee:

lunlikyb@163.com 

研究实施负责(组长)单位:

湖南省人民医院 

Primary sponsor:

Hunan Provincial People's Hospital 

研究实施负责(组长)单位地址:

湖南省长沙市解放西路61号 湖南省人民医院第二住院楼10楼血液科 

Primary sponsor's address:

61 Jiefang Road West, Changsha, Hunan, 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):

湖南

市(区县):

长沙

Country:

China

Province:

Hu'nan

City:

Changsha

单位(医院):

湖南省人民医院

具体地址:

湖南省长沙市解放西路61号 湖南省人民医院第二住院楼10楼血液科

Institution
hospital:

Hunan Provincial People's Hospital

Address:

61 Jiefang Road West, Changsha, Hunan, China

国家:

中国

省(直辖市):

天津

市(区县):

 

Country:

China

Province:

Tianjin

City:

 

单位(医院):

天津天锐生物科技有限公司

具体地址:

天津市空港经济区环河北路76号空港商务园西区19号楼

Institution
hospital:

Timmune Biotech Inc.

Address:

19th Building, Airport Economic Zone, 76 Huanhe Road North, Tianjin, China

经费或物资来源:

天津天锐生物科技有限公司 

Source(s) of funding:

Timmune Biotech Inc. 

研究疾病:

CD19+复发难治性非霍奇金淋巴瘤 

Target disease:

CD19-positive Refractory/Relapsed non-Hodgkin lymphoma 

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+II期 

Study phase:

I+II (Phase I+Phase II) 

研究目的:

TriCAR-T-CD19细胞介导CD19+复发难治性非霍奇金淋巴瘤的过继免疫治疗的安全性,耐受性及效果 

Objectives of Study:

This phase I trial is to investigate the safety, possible side effects and efficacy of TriCAR-T-CD19 adoptive therapy in treating patients with CD19-positive Refractory/Relapsed non-Hodgkin lymphoma. 

药物成份或治疗方案详述:

受试者首先被给予氟达拉滨和环磷酰胺组成的淋巴细胞清除性化疗,之后一次性静脉输注0.5-1×10^6 TriCAR+ T cells/kg的CD19-TriCAR 修饰的自体T细胞 

Description for medicine or protocol of treatment in detail:

A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by a single infusion of CD19-TriCAR transduced autologous T cells administered intravenously at a target dose of 0.5-1 x 10^6 anti-CD19 TriCAR+ T cells/kg 

研究设计:

连续病例 

Study design:

Case series 

纳入标准:

1.受试者必须签署湖南省人民医院医学伦理委员会批准的书面知情同意书并署上日期。知情同意书必须在进行任何方案相关程序(不属于受试者常规医疗的部分内容)之前签署; 2.受试者必须愿意而且能够遵守日程表规定的访视、治疗方案、实验室检查及遵守研究的其他要求; 3.组织学或细胞学确诊患有CD19+非霍奇金淋巴瘤患者; 4.复发难治CD19+非霍奇金淋巴瘤患者需满足以下条件之一:①结束治疗后6个月内复发患者;②接受标准R-CHOP方案或CHOP方案(针对CD20-)化疗中疾病仍进展者;③接受自体造血干细胞移植1年内疾病进展(经组织学确诊);对挽救治疗无效; 5.目前无标准治疗; 6.必须至少有一个可测量的病灶(依据淋巴瘤国际工作组标准); 7.签署知情同意书时年龄18岁-65岁,性别不限; 8.预计生存期≥12周; 9.ECOG体力状况评分为0或1; 10.开始细胞输注研究前,按具有免疫抑制作用的剂量(强的松>10mg/d或等效剂量)应用的全身用药(如皮质类固醇)必须已经停药至少4周; 11.所有既往治疗相关的不良反应必须恢复至1度或1度以下,脱发除外,外周神经毒性不超过2度; 12.筛查所做的实验室检查值必须符合下列标准: - 中性粒细胞≥1x10^9/L; - 血小板≥50x10^9/L; - 血红蛋白≥70g/L; - 肌酐≤1.5倍正常上限; - 谷草转氨酶≤2.5xULN;谷丙转氨酶≤2.5xULN; - 总胆红素≤1.5xULN(Gilbert综合征受试者除外,这些受试者的总胆红素必须<30mg/L); 13.育龄期妇女必须保证研究期间不怀孕 

Inclusion criteria

1. All subjects must personally sign and date the consent form before initiating any study specific procedures or activities; 2. All subjects must be able to comply with all the scheduled procedures in the study; 3. Histologically or cytologically confirmed CD19 positive non-Hodgkin lymphoma; 4. Chemotherapy-refractory disease, defined as one or more of the following: Relapsed in 6 months after most recent therapy; Progressive disease in the standard R-CHOP or CHOP chemotherapy; Disease progression or relapsed in ≤12 months of ASCT (must have biopsy proven recurrence in relapsed subjects); If salvage therapy is given post-ASCT, the subject must have had no response to or relapsed after the last line of therapy. 5. No available standard therapy; 6. At least one measurable lesion per revised IWG Response Criteria; 7. Aged 18 to 65 years; 8. Expected survival ≥12 weeks; 9. Eastern cooperative oncology group (ECOG) performance status of 0 or 1; 10. Systematic usage of immunosuppressive drug or corticosteroid must have been stopped for more than 4 weeks; 11. All other treatment induced adverse events must have been resolved to ≤grade 1; 12. Laboratory tests must fulfill the following criteria: ANC ≥ 1000/uL, HGB >70g/L, Platelet count ≥ 50,000/uL, Creatinine clearance ≤1.5 ULN, Serum ALT/AST ≤2.5 ULN, Total bilirubin ≤1.5 ULN (except in subjects with Gilbert's syndrome); 13. Female must be not pregnant during the study. 

排除标准:

1.既往有恶性肿瘤病史(除外:非黑色素瘤皮肤癌或原位腺癌(如膀胱、子宫、乳腺)、滤泡淋巴瘤,且治愈超过3年); 2.接受过异基因造血干细胞移植; 3.接受过其他CAR-T细胞治疗或基因修饰T细胞治疗; 4.存在难以控制的或需要静脉使用抗生素的真菌、细菌、病毒或其他感染(不包括能有效控制的单纯泌尿系感染或咽炎); 5.既往有或目前有中枢神经系统淋巴瘤、颅内转移、脑脊液内找到淋巴瘤细胞的患者; 6.哺乳期妇女; 7.活动性乙型肝炎病毒感染或丙型肝炎病毒感染; 8.同时系统性使用类固醇药物(使用类固醇吸入剂无需排除); 9.曾使用任何基因治疗产品; 10.器官移植后长期使用免疫抑制药物和正在使用免疫抑制药物的自身免疫病的患者; 11.存在HIV检测阳性病史或筛选时HIV检测呈阳性; 12.计划进行手术、其它疾病史或实验室检查异常或其它情况,导致受试者不适合参加本试验(研究者认为); 13.受试者不愿意遵守研究的各项流程、限制和要求,经研究者判断患者不应该参加研究的。 

Exclusion criteria:

1. History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) or follicular lymphoma unless disease free for at least 3 years; 2. History of allogeneic stem cell transplantation; 3. Prior other CAR therapy or other genetically modified T cell therapy; 4. Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management. Simple UTI and uncomplicated bacterial pharyngitis are permitted if responding to active treatment; 5. Subjects with detectable cerebrospinal fluid malignant cells, or brain metastases, or with a history of CNS lymphoma, cerebrospinal fluid malignant cells or brain metastases; 6. Lactating women; 7. Active infection with hepatitis B (HBsAG positive) or hepatitis C virus (anti-HCV positive); 8. Subjects need systematic usage of corticosteroid; 9. History of any gene therapy; 10. Subjects need systematic usage of immunosuppressive drug; 11. Known history of infection with HIV; 12. Planed operation, history of other related disease, or any other related laboratory tests restrict patients for the study; 13. Other reasons the investigator think the patient may not be suitable for the study. 

研究实施时间:

Study execute time:

From2018-01-01To 2020-12-31 

干预措施:

Interventions:

组别:

Case series

样本量:

6

Group:

Case series

Sample size:

干预措施:

TriCAR-T-CD19细胞输注

干预措施代码:

 

Intervention:

TriCAR-T-CD19 cell infusion

Intervention code:

研究实施地点:

Countries of recruitment and research settings:

国家:

中国 

省(直辖市):

湖南 

市(区县):

长沙 

Country:

China 

Province:

Hunan 

City:

Changsha 

单位(医院):

湖南省人民医院 

单位级别:

三甲医院 

Institution
hospital:

Hunan Provincial People's Hospital  

Level of the institution:

Tertiary 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:

 

指标中文名:

疗效

指标类型:

次要指标 

Outcome:

efficacy

Type:

Secondary 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:

白细胞

组织:

 

Sample Name:

leukocyte

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):

无随机方法

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

non-randomized

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

原始数据公开时间:

The time of sharing IPD:

试验完成后6个月内公开/Within six months after the trial complete

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):

20201231

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

20201231

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:

病例记录表

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

Case Record Form

数据管理委员会:

Data Managemen Committee:

暂未确定/Not yet