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An early exploratory study of GC012F injection in the treatment of CD19 and/or BCMA positive relapsed or refractory B-cell non-Hodgkin's lymphoma
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注册号:

Registration number:

ChiCTR2100047061 

最近更新日期:

Date of Last Refreshed on:

2022-01-18 

注册时间:

Date of Registration:

2021-06-07 

注册号状态:

预注册  

Registration Status:

Prospective registration  

注册题目:

请与我们联系上传伦理审批文件。 GC012F注射液治疗CD19和/或BCMA阳性复发或难治性B细胞非霍奇金淋巴瘤的探索性临床研究 

Public title:

An early exploratory study of GC012F injection in the treatment of CD19 and/or BCMA positive relapsed or refractory B-cell non-Hodgkin's lymphoma 

注册题目简写:

 

English Acronym:

 

研究课题的正式科学名称:

GC012F注射液治疗CD19和/或BCMA阳性复发或难治性B细胞非霍奇金淋巴瘤的探索性临床研究 

Scientific title:

An early exploratory study of GC012F injection in the treatment of CD19 and/or BCMA positive relapsed or refractory B-cell non-Hodgkin's lymphoma 

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:

张毅 

研究负责人:

张毅 

Applicant:

Zhang Yi 

Study leader:

Zhang Yi 

申请注册联系人电话:

Applicant telephone:

+86 15138928971 

研究负责人电话:

Study leader's telephone:

+86 15138928971 

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:

yizhang@zzu.edu 

研究负责人电子邮件:

Study leader's E-mail:

yizhang@zzu.edu 

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:

郑州市建设东路1号 

研究负责人通讯地址:

郑州市建设东路1号 

Applicant address:

1 Construction Road East, Zhengzhou, He'nan 

Study leader's address:

1 Construction Road East, Zhengzhou, He'nan 

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:

郑州大学第一附属医院 

Applicant's institution:

The First Affiliated Hospital of Zhengzhou 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:

L2021-Y047-003 

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:

郑州大学第一附属医院科研和临床试验伦理委员会  

Name of the ethic committee:

Ethics Committee of the First Affiliated Hospital of Zhengzhou University  

伦理委员会批准日期:

Date of approved by ethic committee:

2021-05-20 

伦理委员会联系人:

田丽 

Contact Name of the ethic committee:

Tian Li 

伦理委员会联系地址:

郑州市大学路43号 

Contact Address of the ethic committee:

43 Daxue Road, Zhengzhou, He'nan 

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:

郑州大学第一附属医院 

Primary sponsor:

The First Affiliated Hospital of Zhengzhou University  

研究实施负责(组长)单位地址:

郑州市建设东路1号 

Primary sponsor's address:

1 Construction Road East, Zhengzhou, He'nan 

试验主办单位(项目批准或申办者):

Secondary sponsor:

国家:

中国

省(直辖市):

河南

市(区县):

郑州

Country:

China

Province:

He'nan

City:

Zhengzhou

单位(医院):

郑州大学第一附属医院

具体地址:

建设东路1号

Institution
hospital:

The First Affiliated Hospital of Zhengzhou University

Address:

1 Construction Road East

经费或物资来源:

亘喜生物科技(上海)有限公司 

Source(s) of funding:

Gracell Biotechnologies 

研究疾病:

B细胞非霍奇金淋巴瘤 

Target disease:

B-cell non-Hodgkin's lymphoma 

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:

主要目的: 评估GC012F治疗CD19和/或BCMA阳性复发或难治性B细胞非霍奇金淋巴瘤的安全性、耐受性。 次要目的: 1.评估GC012F在体内的增殖与持续情况; 2.评估GC012F治疗复发或难治性B细胞非霍奇金淋巴瘤的有效性; 3.评估GC012F的免疫原性。 

Objectives of Study:

Primary Objective: To evaluate the safety and tolerability of GC012F in relapsed or refractory CD19 and or maybe BCMA positive acute B-cell non-Hodgkin's lymphoma. Secondary Objective: 1. To evaluate the proliferation and persistence of GC012F in vivo; 2. To evaluate the efficacy of GC012F in CD19 and or maybe BCM positive relapsed or refractory acute B-NHL; 3. To evaluate the humoral immune response to chimeric antigen receptor (CAR) after GC012F infusion.  

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18-75岁(含临界值),性别不限; 2.复发或难治性B细胞非霍奇金淋巴瘤: 3. (1)组织病理学确认的B-NHL,包括但不限于下列亚型:非特指型弥漫大B淋巴瘤,高级别B细胞淋巴瘤伴MYC和BCL2和/或BCL6重排(双/三打击淋巴瘤)(DHL/THL),原发纵隔大B淋巴瘤,滤泡淋巴瘤转化的弥漫大B淋巴瘤,滤泡淋巴瘤;边缘区B细胞淋巴瘤;套细胞淋巴瘤; (2)复发难治性侵袭性B-NHL,受试者必须已经使用过蒽环类药物和利妥昔单抗(或其他CD20靶向药)治疗,并且已经接受过至少两线的治疗或自体造血干细胞移植(auto-HSCT)后复发、未缓解或进展; (3)复发难治性惰性B-NHL,受试者必须已经使用过蒽环类药物和利妥昔单抗(或其他CD20靶向药)治疗,并且已经接受过至少两线的治疗或自体造血干细胞移植(auto-HSCT)后且在末线治疗后730天内复发、未缓解或进展; (4)若受试者既往曾接受过CAR-T治疗,需体内检测不到既往输注的CAR-T细胞或距既往最近一次CAR-T回输已经超过至少60天。 4.根据淋巴瘤的Lugano反应标准(Cheson2014, 见附录1),至少有一个可测量病灶,之前接受过放疗的病灶作为可测量病灶必须放疗完成后记录为进展: (1)结节性病灶长径≥15mm,短径不纳入考虑; (2)结外病灶(淋巴结或结节性病灶之外,包括肝和脾)长径≥10mm,短径不纳入考虑。 5.ECOG评分≤2分; 6.预计生存期≥90天; 7.肿瘤组织CD19和/或BCMA表达阳性; 8.器官功能储备良好: (1)肌酐清除率(Cockcroft-Gault法)>60ml/min:男性肌酐清除率=[(140-年龄)×体重(kg)]/[0.818×肌酐(umol/L)];女性肌酐清除率=[(140-年龄)×体重(kg)×0.85]/[0.818×肌酐(umol/L)]; (2)血清ALT及AST<2.5×ULN(肝转移病人AST及ALT≤5×ULN); (3)血清总胆红素<1.5×ULN(Gilbert’s综合征≤3×ULN); (4)经超声心动图诊断受试者左心室射血分数(LVEF)>50%; (5)室内空气环境下基础指末饱和度>92%。 9.具有充足的骨髓储备,定义为:嗜中性粒细胞绝对值(ANC)> 1.0×10^9/L;淋巴细胞绝对值(ALC)≥ 0.3×10^9/L;血小板(PLT)≥ 50 ×10^9/L; 10.育龄期女性患者必须处于非哺乳期,有生育能力的女性筛选期的高敏感性血清妊娠试验必须为阴性,所有受试者须在整个治疗期间和细胞回输治疗后730天内采用经医学认可的避孕措施(如宫内节育器,避孕药),男性受试者还需避免精子捐献; 11.可建立静脉通路,经研究者判断可进行外周血单个核细胞采集; 12.自愿签署知情同意书; 13.患者能够与研究者作良好的沟通,愿意并能够遵从研究计划,依照研究规定完成研究。 

Inclusion criteria

1. Aged 18 to 75 years(including cut-off value), no gender limit; 2. Relapsed or refractory B-cell non-Hodgkin's lymphoma: 3. (1) B-NHL confirmed by histopathology, including but not limited to the following subtypes: non-specific diffuse large B lymphoma, high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangement (double/triple hit Lymphoma) (DHL/THL), primary mediastinal large B lymphoma, diffuse large B lymphoma transformed from follicular lymphoma, follicular lymphoma; marginal zone B cell lymphoma; mantle cell lymphoma; (2) For relapsed and refractory aggressive B-NHL, the subject must have been treated with anthracyclines and rituximab (or other CD20 targeted drugs), and have received at least two lines of treatment or Recurrence, non-remission or progression after auto-HSCT; (3) For relapsed and refractory indolent B-NHL, the subject must have been treated with anthracyclines and rituximab (or other CD20 targeted drugs), and have received at least two lines of treatment or autologous After hematopoietic stem cell transplantation (auto-HSCT) and within 730 days after last-line treatment, recurrence, no remission or progression; (4) If the subject has received CAR-T treatment in the past, the CAR-T cells previously infused must not be detected in the body or it has been more than 60 days since the most recent CAR-T reinfusion. 4. According to the Lugano response criteria of lymphoma (Cheson2014, see Appendix 1), there is at least one measurable lesion, and the lesions that have received radiotherapy before are regarded as measurable lesions and must be recorded as progress after the completion of radiotherapy: (1) The long diameter of nodular lesions is 15mm, and the short diameter is not considered; (2) Extranodal lesions (except lymph nodes or nodular lesions, including liver and spleen) with long diameter >=10mm, short diameter is not considered. 5. ECOG score <= 2 points; 6. The expected survival period is >= 90 days; 7. Positive expression of CD19 and/or BCMA in tumor tissue; 8. Good organ function reserve: (1) Creatinine clearance rate (Cockcroft-Gault method) > 60ml/min: Male creatinine clearance rate=[(140-age) x weight (kg)]/[0.818 x creatinine (umol/L)]; female creatinine clearance rate =[(140-age) x weight (kg)x 0.85]/[0.818 x creatinine (umol/L)]; (2) Serum ALT and AST < 2.5xULN (AST and ALT <= 5xULN in patients with liver metastasis); (3) Serum total bilirubin < 1.5xULN (Gilberts syndrome <= 3 x ULN); (4) The subject's left ventricular ejection fraction (LVEF) > 50% was diagnosed by echocardiography; (5) The basic index saturation in the indoor air environment is > 92%. 9. Sufficient bone marrow reserve, defined as: absolute value of neutrophils (ANC)> 1.0x10^9/L; absolute value of lymphocytes (ALC) >= 0.3x10^9/L; platelets (PLT) >= 50 x10^9/L; 10. Female patients of childbearing age must be in the non-lactating period, and the high-sensitivity serum pregnancy test during the screening period of fertile women must be negative. Approved contraceptive measures (such as intrauterine devices, contraceptives), male subjects also need to avoid sperm donation; 11. Venous access can be established, and peripheral blood mononuclear cells can be collected by the researcher's judgment; 12. Voluntarily sign the informed consent form; 13. The patient can communicate well with the researcher, is willing and able to follow the research plan, and complete the research in accordance with the research regulations. 

排除标准:

1.活动性中枢神经系统侵犯; 2.患有其他恶性肿瘤,以下情形除外:已治愈的非黑色素瘤皮肤癌、宫颈癌原位癌、局限性前列腺癌、浅表性膀胱癌、导管原位癌、其他无病生存期超过5年的恶性肿瘤; 3.下列任意一项病毒学检测结果为阳性:HIV;HCV;HBsAg;HBcAb阳性,同时检测到HBV DNA拷贝数阳性;TPPA; 4.入组前28天内接种过活疫苗; 5.入组前45天内接受过自体干细胞移植,既往接受过异基因造血干细胞移植; 6.经研究者判断存在需要在研究期间使用系统性皮质类固醇治疗或其他免疫抑制药物治疗的合并症; 7.入组前28天内接受过CNS定向放疗; 8.既往治疗引起的急性毒副反应未恢复至1级或以下(血液学毒性及脱发除外); 9.已知对环磷酰胺或氟达拉滨存在危及生命的超敏反应或其他不耐受的情况或严重过敏体质; 10.活动性自身免疫性疾病(包括但不限于系统性红斑狼疮、干燥综合征、类风湿关节炎、牛皮癣、多发性硬化症、炎症性肠病、桥本甲状腺炎等,除外仅通过激素替代治疗可以控制的甲状腺功能减退); 11.入组前28天内接受过全身麻醉的大手术,或未从既往手术治疗中恢复并获得临床稳定,或预期在研究过程中需要进行全身麻醉的大手术; 12.在入组前28天内使用过其他临床研究药物; 13.入组前180天内患有任何不稳定的循环系统疾病,包括但不限于不稳定型心绞痛、心肌梗死、心力衰竭[纽约心脏病协会(NYHA)分级≥III级]、需要药物治疗的严重心律失常,或入组前180天内进行过心脏血管成形术或冠状动脉支架植入术或心脏搭桥术; 14.存在中枢神经系统病史或疾病,如癫痫、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; 15.筛选时存在不可控的活动性感染(例如败血症、菌血症、真菌血症、病毒血症); 16.研究者认为不适合参加本临床研究的其他情况。 

Exclusion criteria:

1. Active central nervous system violations; 2. Suffering from other malignant tumors, except for the following situations: cured non-melanoma skin cancer, cervical cancer in situ, localized prostate cancer, superficial bladder cancer, ductal carcinoma in situ, other disease-free survival periods exceeding 5 Years of malignant tumors; 3. The result of any one of the following virological tests is positive: HIV; HCV; HBsAg; HBcAb positive, and HBV DNA copy number is positive at the same time; TPPA; 4. Live vaccines have been vaccinated within 28 days before enrollment; 5. Received autologous stem cell transplantation within 45 days before enrollment, and received allogeneic hematopoietic stem cell transplantation in the past; 6. The investigator judges that there are comorbidities that require the use of systemic corticosteroid therapy or other immunosuppressive drugs during the study period; 7. Received CNS directional radiotherapy within 28 days before enrollment; 8. Acute side effects caused by previous treatment have not recovered to Grade 1 or below (except for hematological toxicity and hair loss); 9. Known to have life-threatening hypersensitivity or other intolerances or severe allergies to cyclophosphamide or fludarabine; 10. Active autoimmune diseases (including but not limited to systemic lupus erythematosus, Sjogrens syndrome, rheumatoid arthritis, psoriasis, multiple sclerosis, inflammatory bowel disease, Hashimotos thyroiditis, etc., except only through hormone replacement Treatment of controllable hypothyroidism); 11. Received major surgery under general anesthesia within 28 days before enrollment, or failed to recover from previous surgical treatments and achieved clinical stability, or expected major surgery under general anesthesia during the study; 12. Used other clinical research drugs within 28 days before enrollment; 13. Suffered from any unstable circulatory system disease within 180 days before enrollment, including but not limited to unstable angina, myocardial infarction, heart failure [New York Heart Association (NYHA) grade >= grade iii], serious medical treatment Arrhythmia, or cardiovascular angioplasty, coronary stent implantation or heart bypass surgery within 180 days before enrollment; 14. There is a history or disease of the central nervous system, such as epilepsy, cerebral ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease involving the CNS; 15. Uncontrollable active infection (such as sepsis, bacteremia, fungemia, viremia) during screening; 16. Other situations that the investigator believes are not suitable for participating in this clinical study. 

研究实施时间:

Study execute time:

From2021-06-18To 2024-06-18 

征募观察对象时间:

Recruiting time:

From2021-06-18To 2024-06-18 

干预措施:

Interventions:

组别:

试验组

样本量:

12

Group:

Experimental group

Sample size:

干预措施:

GC012F治疗

干预措施代码:

Intervention:

GC012F treatment

Intervention code:

研究实施地点:

Countries of recruitment and research settings:

国家:

中国 

省(直辖市):

河南 

市(区县):

 

Country:

China 

Province:

He'nan 

City:

 

单位(医院):

郑州大学第一附属医院 

单位级别:

三级甲等 

Institution
hospital:

The First Affiliated Hospital of Zhengzhou University  

Level of the institution:

Tertiary A 

测量指标:

Outcomes:

指标中文名:

剂量限制性毒性

指标类型:

主要指标 

Outcome:

dose-limiting toxicity

Type:

Primary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

实验室检查

指标类型:

主要指标 

Outcome:

laboratory examination

Type:

Primary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

生命体征

指标类型:

主要指标 

Outcome:

vital signs

Type:

Primary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

体格检查

指标类型:

主要指标 

Outcome:

physical examination

Type:

Primary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

复制型慢病毒

指标类型:

主要指标 

Outcome:

replication competent lentivirus

Type:

Primary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

外周血细胞因子

指标类型:

次要指标 

Outcome:

cytokines in peripheral blood

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

总生存期

指标类型:

次要指标 

Outcome:

overall survival

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

无进展生存期

指标类型:

次要指标 

Outcome:

progression-free survival

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

缓解持续时间

指标类型:

次要指标 

Outcome:

duration of response

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:

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:

标本中文名:

肿瘤组织

组织:

Sample Name:

Tumor tissue

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 75 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):

非随机

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

Non-randomized

盲法:

N/A

Blinding:

N/A

试验完成后的统计结果(上传文件):

点击下载

Calculated Results ater
the Study Completed(upload file):

download

是否共享原始数据:

IPD sharing

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):

未说明 请阅读网页注册指南中关于 原始数据共享 的内容。

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

Not stated

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:

本研究使用电子数据采集系统(EDC)建立电子病例报告表(eCRF),eCRF根据方案和病例报告表设计,进行数据采集。本试验使用北京百奥知信息科技有限公司的EDC 2.9.0系统进行数据采集和管理。 本试验实验室数据根据各中心提供的实验室正常值范围进行核查。各中心的实验室参考范围由各中心监查员(CRA)汇总并提供给数据管理项目经理(DMPM),DMPM需对收到的实验室参考范围检查并确认,以备实验室数据核查使用。实验室参考范围应当包括但不仅限于中心名称、实验室指标名称、性别、参考范围、生效时间等,并由该中心的主要研究者签字确认或相关人员(如实验室主任、机构办公室)盖章或签字确认。如试验过程中遇到任何实验室参考值范围的变化,监查员应及时通知DMPM,重新提供相应的文件。 本临床试验外部数据为生物样本分析数据。外部数据由中心实验室无锡观合医学检验所有限公司及上海精翰生物科技有限公司提供,数据传输双方签订协议。数据管理项目经理(DMPM)根据外部数据传输频率,定期进行外部检查或者一致性核查。数据管理部经理(DMM)与外部数据供应商保持良好的交流渠道及解决问题的途径。

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

This study used the Electronic Data Acquisition System (EDC) to establish an electronic case reporting form (eCRF), which was designed to collect data according to the program and case reporting table. This experiment uses the EDC 2.9.0 system of Beijing Baiozhi Information Technology Co., Ltd. for data collection and management. The laboratory data are verified according to the normal value range of the laboratory provided by each center. The laboratory reference scopes for each center are summarized by the central inspectors (CRAs) and provided to the Data Management Project Manager (DMPM), who is required to check and confirm the laboratory reference scope received for laboratory data verification. The scope of laboratory reference shall include, but not be limited to, the name of the centre, the name of the laboratory indicator, gender, reference scope, effective time, etc., and shall be signed by the principal researcher of the centre or sealed or confirmed by the relevant person (e.g. laboratory director, agency office). If any changes in the range of laboratory reference values are encountered during the test, the inspector shall promptly notify the DMM and re-provide the appropriate documents. The external data of this clinical trial are biological sample analysis data. The external data is provided by the central laboratory Wuxi Guanhe Medical Laboratory Co., Ltd. and Shanghai Jinghan Biotech Co., Ltd., and the data transmission parties sign an agreement. The Data Management Project Manager (DMPM) conducts regular external checks or consistency checks based on the frequency of external data transfers. The Data Management Manager (DMM) maintains good communication channels and problem solving channels with external data providers.

数据与安全监察委员会:

Data and Safety Monitoring Committee:

无/No

注册人:

Name of Registration:

 2021-06-07
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