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：	ChiCTR1800015226
最近更新日期： Date of Last Refreshed on：	2018-03-16 20:45:24
注册时间： Date of Registration：	2018-03-16 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	嵌合抗原受体T细胞治疗CD19阳性复发难治性B细胞来源的血液系统恶性肿瘤的临床应用研究
Public title：	The clinical application of chimeric antigen receptor T cells in the treatment of CD19 positive recurrence of refractory b-cell source of blood system malignant tumor.
注册题目简写：
English Acronym：
研究课题的正式科学名称：	嵌合抗原受体T细胞治疗CD19阳性复发难治性B细胞来源的血液系统恶性肿瘤的临床应用研究
Scientific title：	The clinical application of chimeric antigen receptor T cells in the treatment of CD19 positive recurrence of refractory b-cell source of blood system malignant tumor
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：	李刚	研究负责人：	杨林
Applicant：	Gang Li	Study leader：	Lin Yang
申请注册联系人电话： Applicant telephone：	+86 0551 65728070	研究负责人电话： Study leader's telephone：	+86 13390897122
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：	gang.li@persongen.com.cn	研究负责人电子邮件： Study leader's E-mail：	lin.yang@persongen.com.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：	安徽省合肥市高新区海关路4号	研究负责人通讯地址：	安徽省合肥市高新区海关路4号
Applicant address：	4 Haiguan Road, High-tech Zone, Hefei, Anhui, China	Study leader's address：	4 Haiguan Road, High-tech Zone, Hefei, Anhui, China
申请注册联系人邮政编码： Applicant postcode：	230000	研究负责人邮政编码： Study leader's postcode：	230000
申请人所在单位：	博生吉安科细胞技术有限公司
Applicant's institution：	PersonGen Anke Cellular therapeutics co.,Ltd
研究负责人所在单位：	博生吉安科细胞技术有限公司
Affiliation of the Leader：	PersonGen·Anke Cellular therapeutics Co., Ltd.

是否获伦理委员会批准：	否
Approved by ethic committee：	No
伦理委员会批件文号： Approved No. of ethic committee：		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：
Name of the ethic committee：
伦理委员会批准日期： Date of approved by ethic committee：	2013-08-26 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：

苏州大学附属第二医院

Primary sponsor：

The Second Affiliated Hospital of Soochow University

研究实施负责（组长）单位地址：

苏州市三香路1055号

Primary sponsor's address：

1055 Sanxiang Road, Suzhou, Jiangsu, 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)：	江苏省	市(区县)：	苏州市
Country：	China	Province：	Jiangsu	City：	suzhou city
单位(医院)：	苏州大学附属第二医院	具体地址：	苏州市三香路1055号
Institution hospital：	The Second Affiliated Hospital of Soochow University	Address：	1055 Sanxiang Road, Suzhou, Jiangsu, China

经费或物资来源：

自筹经费

Source(s) of funding：

Self-financing

研究疾病：

血液系统恶性肿瘤

Target disease：

blood system malignant tumor

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：

治疗新技术临床试验

Study phase：

New Treatment Measure Clinical Study

研究设计：

连续入组

Study design：

Sequential

研究目的：

评价嵌合抗原受体T细胞治疗CD19阳性复发难治性B细胞来源的血液系统恶性肿瘤的有效性、安全性。

Objectives of Study：

To evaluate the efficacy and safety of chimeric antigen receptor T cells in the treatment of hematological malignancies with CD19 positive recurrence of refractory B cells.

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 to 70 years old;
2. Morphological analysis showed that the load of bone marrow lymphoma was greater than 5%;
3. Expected survival time: > 12 weeks;
4. The Attending physician believe that there is no other feasible and effective alternative treatment, such as hematopoietic stem cell transplantation;
5. Recurrent/refractory B-cell acute lymphocytic leukemia (ALL):
(1) Grade 2 or higher bone marrow relapse objective remission rate (OR)
(2) Any BM relapse after allogeneic SCT and must be > 6 months from SCT at the time of CTL019 infusion OR
(3) Refractory as defined by not achieving a CR after 2 cycles of a standard chemotherapy regimen chemotherapy regimen or chemorefractory as defined by not achieving a CR after 1 cycle of standard chemotherapy for relapse leukemia OR
(4) Patients with Philadelphia chromosome positive (Ph+) ALL are eligible if they are intolerant to or have failed 2 lines of tyrosine kinase inhibitor therapy (TKI), or if TKI therapy is contraindicated OR
(5) Ineligible for allogeneic SCT.
6. For relapsed patients, CD19 tumor expression demonstrated in bone marrow or peripheral blood by flow cytometry within 3 months of study entry;
7. Expression of CD19 on lymphoma cells: immunohistochemical detection >15% or flow cytometry detection >30%;
8. Adequate organ function defined as:
(1) Renal function defined as (Calculated creatinine clearance or radioisotope Glomerular Filtration Rate (GFR) > 60 mL/min/1.73 m2 OR serum creatinine based on age/gender
(2) Alanine Aminotransferase (ALT) < 5 times the upper limit of normal (ULN) for age;
(3) Bilirubin < 2.0 mg/dL;
(4) Must have a minimum level of pulmonary reserve defined as ≤Grade 1 dyspnea and pulse oxygenation > 91% on room air;
(5) Left Ventricular Shortening Fraction (LVSF) ≥ 28% confirmed by echocardiogram, or Left Ventricular Ejection Fraction (LVEF) ≥ 45% confirmed by echocardiogram or MUGA within 7 days of screening;
9. Karnofsky (age ≥ 16 years) or Lansky (age < 16 years) performance status ≥ 50 at screening;
10. Signed written informed consent and assent forms (if applicable) must be obtained prior to any study procedures;
11. Once all other eligibility criteria are confirmed, must have an apheresis product of non-mobilized cells received and accepted by the manufacturing site. Note: Apheresis product will not be shipped to or assessed for acceptance by the manufacturing site until documented confirmation of all other eligibility criteria is received.

排除标准：

1.孤立的髓外疾病复发
2.患者伴有下列的遗传综合征：Fanconi综合征、Kostmann综合征、Shwachman综合征或任何已知的骨髓衰竭综合征，唐氏综合症患者不列入排除标准
3.患者患有Burkitt's淋巴瘤/白血病（即患者患有成熟B细胞ALL，淋巴瘤B细胞表面免疫球蛋白阳性（sIg+）并且轻链为Kappa型或Lambda型，形态学为FAB L3型或MYC异位表达）
4.既往有恶性肿瘤病史，但皮肤或宫颈原位癌治愈患者以及非活动性肿瘤患者不列入排除标准
5.既往使用过基因治疗
6.既往使用过抗CD19/CD3联合治疗或者其他任何抗CD19治疗
7.筛选时患有乙型或丙型肝炎或携带HBV/HCV，或者伴有其他未控制的感染
8.筛选时伴有HIV感染
9.2级-4级急性或慢性移植物抗宿主反应（GVHD）
10.采用下列药物治疗：
A.类固醇：CART-19回输前72小时内禁止使用，但是可以使用生理性类固醇治疗剂量（< 6 - 12 mg/m2/day）或等效的氢化可的松
B.异基因细胞治疗：CART-19回输前6周内不可进行任何供体淋巴细胞输注（DLI）
C.GVHD治疗：CART-19回输前4周内必须停止任何GVHD治疗（如钙调铃酸酶抑制剂、氨甲喋呤、麦考酚酯、类固醇（见上）、雷帕霉素、沙利度胺或免疫抑制抗体（如抗CD20/TNF/IL6/IL6R））
D.化疗：i. 下列药物在CART-19回输前至少停用1周，同时最好不要伴随或者跟随淋巴细胞清除化疗方案：羟基脲、长春新碱、6-巯基嘌呤、6-硫鸟嘌呤、甲氨蝶呤<25 mg/m2、阿糖胞苷< 10 mg/m2/day、门冬酰胺酶；ii. 下列药物在CART-19回输前至少停用4周：补救性化疗（如氯法拉滨、阿糖胞苷> 100 mg/m2、蒽环类药物、环磷酰胺），淋巴细胞清除化疗药物不列入排除标准
E.中枢神经系统（CNS）疾病预防：CNS预防治疗在CART-19回输前至少停用1周（如脊髓注射甲氨喋呤）
11.恶性肿瘤CNS浸润，参照美国国家综合癌症网络（NCCN）指南CNS-3。注：患者患有CNS疾病但已得到有效治疗不列入排除标准，患者在筛选前30天内不能参与药物试验研究
12.怀孕或者哺乳期的女性：女性试验参与者回输前48小时须进行血清或尿妊娠检测，检测结果为阳性
13.育龄期女性患者以及所有男性患者在CART-19回输后1年内未采取有效避孕手段

Exclusion criteria：

1. Isolated extra-medullary disease relapse
2. Patients with concomitant genetic syndrome: such as patients with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome. Patients with Down Syndrome will not be excluded.
3. Patients with Burkitt's lymphoma/leukemia (i.e. patients with mature B-cell ALL, leukemia with B-cell [surface Immunoglobulin (sIg) positive and kappa or lambda restricted positivity] ALL, with FAB L3 morphology and /or a MYC translocation)
4. Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease
5. Prior treatment with gene therapy product
6. Treatment with any prior anti-CD19/anti-CD3 therapy, or any other anti-CD19 therapy
7. Active or latent hepatitis B or active hepatitis C (test within 8 weeks of screening), or any uncontrolled infection at screening
8. HIV positive test within 8 weeks of screening
9. Presence of Grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD)
10. The following medications are excluded:
(1) Steroids: Therapeutic systemic doses of steroids must be stopped > 72 hours prior to CART-19 infusion. However, the following physiological replacement doses of steroids are allowed: < 12 mg/m2/day hydrocortisone or equivalent
(2) Allogeneic cellular therapy: Any donor lymphocyte infusions (DLI) must be completed > 6 weeks prior to CART-19 infusion
(3) GVHD therapies: Any systemic drug used for GVHD must be stopped > 4 weeks prior to CART-19 infusion to confirm that GVHD recurrence is not observed (e.g. calcineurin inhibitors, methotrexate or other chemotherapy drugs, mycophenolyate, rapamycin, thalidomide, or immunosuppressive antibodies such as anti-CD20 (rituximab), anti-tumor necrosis factor [anti-TNF], anti-interleukin 6 [anti-IL6] or anti-interleukin 6 receptor [anti-IL6R], systemic steroids).
(4) Chemotherapy:
Tyrosine kinase inhibitors and hydroxyurea must be stopped > 72 hours prior to CART-19 infusion
The following drugs must be stopped > 1 week prior to CART-19 infusion and should not be administered concomitantly or following lymphodepleting chemotherapy: vincristine, 6-mercaptopurine, 6-thioguanine, methotrexate < 25 mg/m2, cytosine arabinoside < 100 mg/m2/day, asparaginase (non-pegylated);
The following drugs must be stopped >2 weeks prior to CART-19 infusion: salvage chemotherapy (e.g. clofarabine, cytosine arabinoside > 100 mg/m2, anthracyclines, cyclophosphamide, methotrexate ≥ 25 mg/m2), excluding the required lymphodepleting chemotherapy drugs;
(5) CNS prophylaxis treatment must be stopped > 4 week prior to CART-19 infusion (e.g. intrathecal methotrexate) f. Radiotherapy;
11. women who were pregnant or lactation: the female test participants had to test the serum or urine pregnancy 48 hours before the transfusion, and the results were positive;
12. women of childbearing age and all male patients did not take effective contraception within 1 years after CART-19 return.

研究实施时间：

Study execute time：

从 From 2018-03-16 00:00:00至 To 2020-03-16 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2018-03-16 00:00:00 至 To 2020-03-16 00:00:00

干预措施：

Interventions：

组别：	Case series	样本量：	10
Group：	Case series	Sample size：	10
干预措施：	细胞输注	干预措施代码：
Intervention：	infusion of cell	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	江苏省	市(区县)：	苏州市
Country：	China	Province：	Jiangsu	City：	jiangsu city
单位(医院)：	苏州大学附属第二医院	单位级别：	三级甲等
Institution hospital：	The Second Affiliated Hospital of Soochow University	Level of the institution：	Tertiary A Hospital

测量指标：

Outcomes：

指标中文名：	完全缓解	指标类型：	主要指标
Outcome：	complete relieved	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：	外周血
Sample Name：	Blood	Tissue：	Peripheral blood
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	岁 years
最大 Max age	70	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）：

每一个患者都有一个特有的随机号，随机号由研究者制定。

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

Each subject has a unique random number, which is sorted by the researcher's set

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

公开/Public

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

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）：	2020-9-16日前公布数据结果，共享平台为微信公众号“博生吉细胞治疗”
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	release the data before 2020-9-16, Sharing platform for WeChat,
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：	通过CRF表进行采集
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	Collecting by the CRF table
数据与安全监察委员会： Data and Safety Monitoring Committee：	有/Yes
注册人： Name of Registration：	2018-03-16 20:45:24