ChiCTR2200059551 版本V1.2 版本创建时间2023/02/13 21:40:52 中国临床试验注册中心

审核状态：

Project audit state：

通过审核

Successful

注册号：

Registration number：

 ChiCTR2200059551 

最近更新日期：

Date of Last Refreshed on：

 2022-05-04 11:01:11 

注册时间：

Date of Registration：

 2022-05-04 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

冬凌草联合西药治疗老年MDS/AML及与DNMT3A R882突变关系的临床研究

Public title：

Clinical study on Rabdosia rubescens combined with medicine in the treatment of elderly MDS / AML and its relationship with DNMT3A R882 mutation

注册题目简写：

English Acronym：

研究课题的正式科学名称：

冬凌草联合西药治疗老年MDS/AML及与DNMT3A R882突变关系的临床研究

Scientific title：

Clinical study on Rabdosia rubescens combined with medicine in the treatment of elderly MDS / AML and its relationship with DNMT3A R882 mutation

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：

ChiMCTR2200005965

申请注册联系人：

胡蓉华 

研究负责人：

胡蓉华 

Applicant：

Ronghua HU 

Study leader：

Ronghua HU 

申请注册联系人电话：

Applicant telephone：

 13521423621

研究负责人电话：

Study leader's
telephone：

13521423621

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：

 hurh@163.com

研究负责人电子邮件：

Study leader's E-mail：

 hurh@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：

北京市西城区长椿街45号

研究负责人通讯地址：

北京市西城区长椿街45号

Applicant address：

No.45 Changchun Street，Beijing,China

Study leader's address：

No.45 Changchun Street

申请注册联系人邮政编码：

Applicant postcode：

 100053

研究负责人邮政编码：

Study leader's postcode：

 100053

申请人所在单位：

首都医科大学宣武医院

Applicant's institution：

Xuanwu Hospital, Capital Medical University

研究负责人所在单位：

Affiliation of the Leader：

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：

 临研审【2022】013号

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：

首都医科大学宣武医院伦理委员会

Name of the ethic committee：

Ethics Committee Of Xuanwu Hospital,Capital Medical University

伦理委员会批准日期：

Date of approved by ethic committee：

 2022-02-17 00:00:00

伦理委员会联系人：

吴慧珍

Contact Name of the ethic committee：

Huizhen Wu

伦理委员会联系地址：

Contact Address of the ethic committee：

No.45 Changchun Street, Xicheng Distract

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：

首都医科大学宣武医院

Primary sponsor：

Xuanwu Hospital, Capital Medical University

研究实施负责（组长）单位地址：

首都医科大学宣武医院

Primary sponsor's address：

Xuanwu Hospital, Capital Medical University

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

北京

市(区县)：

Country：

China

Province：

Beijing

City：

单位(医院)：

首都医科大学宣武医院

具体地址：

西城区长椿街45号

Institution
hospital：

Xuanwu Hospital, Capital Medical University

Address：

45 Changchun Street, Xicheng District

经费或物资来源：

首都卫生发展科研专项项目

Source(s) of funding：

Capital health development scientific research project

研究疾病：

急性髓系白血病，骨髓增生异常综合征  

Target disease：

Acute myeloid leukemia and Myelodysplastic syndrome

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：

 治疗新技术临床试验 

Study phase：

New Treatment Measure Clinical Study

研究设计：

随机平行对照 

Study design：

Parallel 

研究目的：

本课题拟以冬凌草甲素选择性作用于DNMT3A R882 基因为靶点，利用已经上市的药物冬凌草片剂联合西药治疗老年MDS/AML观察临床疗效及安全性，探讨伴有DNMT3A突变的老年MDS/AML能否从冬凌草联合西药的治疗中获益，从而为这部分患者的个体化、精准化治疗提供依据。  

Objectives of Study：

This clinical study intends to take oridonin selectively acting on DNMT3A R882 gene as the target, use the listed drug oridonin tablet combined with medicine to treat elderly MDS / AML, observe the clinical efficacy and safety, and explore whether elderly MDS/AML patients with DNMT3A mutation can benefit from the treatment of oridonin combined withmedicine, so as to provide basis for individualized and accurate treatment of these patients. This topic intends to take oridonin selectively acting on Dnmt3a r882 gene as the target, use the listed drug oridonin tablet combined with western medicine to treat elderly MDS / AML, observe the clinical efficacy and safety, and explore whether elderly MDS / AML with Dnmt3a mutation can benefit from the treatment of oridonin combined with western medicine, so as to provide basis for individualized and accurate treatment of these patients.

药物成份或治疗方案详述：

 

Description for medicine or protocol of treatment in detail：

 

纳入标准：

1.前述骨髓细胞形态学、免疫学、遗传学、分子生物学确诊的除急性早幼粒细胞白血病以外的急性髓系白血病、骨髓增生异常综合征患者，分型诊断参照2008版世界卫生组织（WHO）诊断分型标准。具体要求如下：
1)急性白血病外周血或骨髓原始细胞≧20%，
2)既往有MDS病史或伴有多系病态造血的AML;
3)有MDS相关的细胞遗传学遗传且没有AML伴重现性细胞遗传学异常的特异性遗传学异常
4)符合WHO标准的MDS，达到治疗标准的；
5)所有以上患者均需有二代测序结果
6）慢性粒-单核细胞白血病（CMML）
2.年龄≥ 60岁，男女不限。
3.不适合常规及强化疗;无造血干细胞移植的机会（无论客观和主观因素）
4.东部肿瘤学协作组体力状态评估(ECOG-PS)为0-3分。
5.通过以下实验室检查指标的要求（在治疗前7天之内进行）：
1) 总胆红素≤（相同年龄段的）正常值上限1.5倍；
2）AST和ALT≤（相同年龄段的）正常值上限2.5倍；
3）血肌酐清除率>30ml/min；
4）心肌酶＜（相同年龄段的）正常值上限2倍；
5）经心脏超声（ECHO）测定心脏射血分数在正常值范围内。

Inclusion criteria

1. For patients with acute myeloid leukemia and myelodysplastic syndrome other than acute promyelocytic leukemia diagnosed by bone marrow cell morphology, immunology, genetics and molecular biology, the classification diagnosis shall refer to the diagnostic classification standard of the World Health Organization (who) in 2008. Specific requirements are as follows:

1) Peripheral blood or bone marrow primordial cells of acute leukemia ≥ 20%,

2) AML with a previous history of MDS or with multilineage morbid hematopoiesis;

3) There is cytogenetic inheritance related to MDS and no specific genetic abnormalities of AML with recurrent cytogenetic abnormalities

4) MDS that meets the WHO standard and meets the treatment standard;

5) All the above patients need to have second-generation sequencing results

6) Chronic myelomonocytic leukemia (CMML)

2. Age ≥ 60, male or female.

3. Not suitable for routine and intensive therapy; No chance of hematopoietic stem cell transplantation (regardless of objective and subjective factors)

4. The ECOG-ps score is 0-3.

5. Pass the requirements of the following laboratory test indicators (within 7 days before treatment):

1) Total bilirubin ≤ (in the same age group) 1.5 times the upper limit of normal value;

2) AST and alt ≤ (in the same age group) are 2.5 times the upper limit of normal value;

3) Serum creatinine clearance rate > 30ml / min;

4) Myocardial enzyme < 2 times the upper limit of normal value (in the same age group);

5) The ejection fraction measured by cardiac ultrasound (echo) was within the normal range.

排除标准：

1）符合世界卫生组织诊断标准（WHO标准）的包括APL及伴有重现性遗传学异常AML。
2）适合常规或强烈化疗，有异基因造血干细胞移植指证者。
3）治疗相关AML，其他肿瘤仍处于活动期或6个月内因其他肿瘤接受了放化疗的患者。
4）世界卫生组织（WHO）AML分类属不另做分类的AML的亚类中急性全髓增殖症伴骨髓纤维化及髓系肉瘤患者。
5）伴有FLT3或IDH2突变的AML/MDS拟加用相应的抑制剂者。
6）单纯伴有5q-、或者SF3B1突变的MDS患者。
7）严重感染性疾病（未治愈的结核病、肺曲霉菌病）。
8）AIDS患者。
9）确诊AML时即有中枢神经系统浸润证据者。
10）需要药物治疗的癫痫、痴呆及其他精神状况异常不能理解或遵从研究方案者。
11）可能干扰受试者参与研究或研究结果评估的药物滥用、医学、心理或社会状况。
12）自愿应用bcl-2抑制剂-维奈克拉及其他靶向药物的AML患者。
13）研究者认为不适合入组者。

Exclusion criteria：

1) APL and AML with reproducible genetic abnormalities were included in those who diagnostic criteria.

2) Suitable for routine or intensive chemotherapy, with evidence of allogeneic hematopoietic stem cell transplantation.

3) Patients with treatment-related AML, other tumors are still active or have received radiotherapy and chemotherapy for other tumors within 6 months.

4) The World Health Organization (who) classification of AML is a subclass of AML not otherwise classified. Patients with acute myeloproliferative disease with bone marrow fibrosis and myelosarcoma.

5) AML / MDS with FLT3 or idh2 mutation intends to add corresponding inhibitors.

6) MDS patients with 5q-, or sf3b1 mutation alone.

7) serious infectious diseases (uncured tuberculosis and pulmonary aspergillosis).

8) AIDS patients.

9) There was evidence of central nervous system infiltration when AML was diagnosed.

10) Epilepsy, dementia and other mental disorders requiring drug treatment who cannot understand or comply with the study protocol.

11) Drug abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or the evaluation of the results of the study.

12) AML patients who voluntarily applied Bcl-2 inhibitor venekla and other targeted drugs.

13) The researchers considered it unsuitable for inclusion.

1) APL and AML with reproducible genetic abnormalities were included in those who diagnostic criteria.

2) Suitable for routine or intensive chemotherapy, with evidence of allogeneic hematopoietic stem cell transplantation.

3) Patients with treatment-related AML, other tumors are still active or have received radiotherapy and chemotherapy for other tumors within 6 months.

4) The World Health Organization (who) classification of AML is a subclass of AML not otherwise classified. Patients with acute myeloproliferative disease with bone marrow fibrosis and myelosarcoma.

5) AML / MDS with FLT3 or idh2 mutation intends to add corresponding inhibitors.

6) MDS patients with 5q-, or sf3b1 mutation alone.

7) serious infectious diseases (uncured tuberculosis and pulmonary aspergillosis).

8) AIDS patients.

9) There was evidence of central nervous system infiltration when AML was diagnosed.

10) Epilepsy, dementia and other mental disorders requiring drug treatment who cannot understand or comply with the study protocol.

11) Drug abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or the evaluation of the results of the study.

12) AML patients who voluntarily applied Bcl-2 inhibitor venekla and other targeted drugs.

13) The researchers considered it unsuitable for inclusion.

研究实施时间：

Study execute time：

从 From 2022-05-16 00:00:00至 To 2024-12-31 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2022-05-23 00:00:00 至 To 2024-12-31 00:00:00

干预措施：

Interventions：

组别：

试验组

样本量：

 80

Group：

Experimental group

Sample size：

干预措施：

阿扎胞苷+冬凌草片

干预措施代码：

Intervention：

Azacitidine+Rabdosia rubescens

Intervention code：

组别：

对照组

样本量：

 80

Group：

Control group

Sample size：

干预措施：

单用阿扎胞苷

干预措施代码：

Intervention：

Azacitidine

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 北京 

市(区县)：

  

Country：

China

Province：

Beijing

City：

单位(医院)：

 首都医科大学宣武医院 

单位级别：

 三级甲等 

Institution
hospital：

Xuanwu Hospital, Capital Medical University

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

客观有效率

指标类型：

主要指标

Outcome：

objective response rate

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 60 岁 years
最大 Max age 85 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）：

随机数字表

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

Random number table

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）：

Calculated Results after
the Study Completed(upload file)：

是否共享原始数据：

IPD sharing

否No

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）：

电子病历平台

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

Electronic medical record platform

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, CRF)

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2022-05-04 11:00:04