ChiCTR2500098586 版本V1.0 版本创建时间2025/03/11 10:02:21 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：

 ChiCTR2500098586 

最近更新日期：

Date of Last Refreshed on：

 2025-03-11 10:02:14 

注册时间：

Date of Registration：

 2025-03-11 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

VA联合吉瑞替尼治疗NPM1mut/FLT3/ITDmut/DNMT3Amut初治AML有效性、安全性的临床研究

Public title：

Clinical study on efficacy and safety of VA combined with Gilteritinib for treatment of de novo AML with NPM1mut/FLT3/ITDmut/DNMT3Amut

注册题目简写：

English Acronym：

研究课题的正式科学名称：

VA联合吉瑞替尼治疗NPM1mut/FLT3/ITDmut/DNMT3Amut初治AML有效性、安全性的临床研究

Scientific title：

Clinical study on efficacy and safety of VA combined with Gilteritinib for treatment of de novo AML with NPM1mut/FLT3/ITDmut/DNMT3Amut

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：

孔繁聪 

研究负责人：

孔繁聪 

Applicant：

Fancong Kong 

Study leader：

Fancong Kong 

申请注册联系人电话：

Applicant telephone：

 +86 189 7093 4599

研究负责人电话：

Study leader's
telephone：

+86 189 7093 4599

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：

 360035477@qq.com

研究负责人电子邮件：

Study leader's E-mail：

 360035477@qq.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：

江西省南昌市南昌县东岳大道1519号南昌大学第一附属医院（象湖院区）

研究负责人通讯地址：

南昌市东湖区永外正街17号

Applicant address：

No. 1519 Dongyue Avenue, Nanchang County, Nanchang City, Jiangxi Province, China

Study leader's address：

17# Yongwai Zhengjie, Nanchang City, Jiangxi Province, 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：

南昌大学第一附属医院

Applicant's institution：

The First Affiliated Hospital of Nanchang University

研究负责人所在单位：

南昌大学第一附属医院

Affiliation of the Leader：

The first affiliated hostipal of nanchang 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：

 IIT2024745

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：

南昌大学第一附属医院IIT项目伦理审查委员会

Name of the ethic committee：

Medical Ethics Committee of the First Affiliated Hospital of Nanchang University

伦理委员会批准日期：

Date of approved by ethic committee：

 2024-11-21 00:00:00

伦理委员会联系人：

舒展

Contact Name of the ethic committee：

Shu Zhan

伦理委员会联系地址：

南昌市东湖区永外正街17号

Contact Address of the ethic committee：

17# Yongwai Zhengjie, Nanchang City, Jiangxi Province, China

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 791 88692201

伦理委员会联系人邮箱：

Contact email of the ethic committee：

 493831410@qq.com

研究实施负责（组长）单位：

南昌大学第一附属医院

Primary sponsor：

The first affiliated hostipal of nanchang university

研究实施负责（组长）单位地址：

南昌市东湖区永外正街17号

Primary sponsor's address：

17# Yongwai Zhengjie, Nanchang City, Jiangxi Province, 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)：

江西

市(区县)：

Country：

China

Province：

Jiangxi

City：

单位(医院)：

南昌大学第一附属医院

具体地址：

南昌市东湖区永外正街17号

Institution
hospital：

The first affiliated hostipal of nanchang university

Address：

17# Yongwai Zhengjie, Nanchang City, Jiangxi Province, China

经费或物资来源：

临床研究培育项目

Source(s) of funding：

clinical research cultivation program of the First Affiliated Hospital of Nanchang University

研究疾病：

具有NPM1、FLT3/ITD及DNMT3A三种突变的初治急性髓系白血病  

Target disease：

De novo AML with NPM1, FLT3/ITD and DNMT3A triple mutations

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：

 II期临床试验 

Study phase：

2

研究设计：

单臂 

Study design：

Single arm 

研究目的：

提高NPM1、FLT3/ITD及DNMT3A三突变初治AML患者诱导缓解率，延长生存期，改善预后。  

Objectives of Study：

To improve the induced remission rate and prolong survival of de novo AML patients with NPM1, FLT3/ITD and DNMT3A triple mutations.

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.根据WHO2022标准诊断为AML；
2.经基因突变检测同时存在NPM1、FLT3/ITD及DNMT3A突变；
3.初诊患者，入组前未接受过其他诱导治疗（包括化疗、去甲基化药物、其他靶向治疗药物）等（羟基脲除外）；
4.ECOG 评分0-2分；
5.肝功能：总胆红素<=正常上限2倍；谷丙转氨酶<=正常上限3倍；谷草转氨酶<=正常上限3倍；（考虑白血病肝脏浸润时，谷丙转氨酶<=正常上限5倍；谷草转氨酶<=正常上限5倍）；
6.肾功能：内生肌酐清除率>=30ml/min；
7.患者必须有能力理解并愿意参加本研究签署知情同意书；

Inclusion criteria

1.Diagnosed with AML according to WHO2022 criteria;
2.AML patients with concurrent NPM1, FLT3/ITD and DNMT3A mutations;
3.De nove AML, not received other induction therapy (including chemotherapy, demethylation drugs, other targeted drugs) before enrollment (except hydroxyurea);
4.ECOG score 0-2;
5.Liver function: Total bilirubin <= 2 × upper limit of normal level (ULN); Glutamic pyruvic transaminase (ALT) <=3 × ULN; Aspartate transaminase (AST) <=3 × ULN; When considering liver infiltration of leukemia cells, ALT <= 5 × ULN; AST <=5 × ULN.
6.Renal function: Endogenous creatinine clearance rate (Ccr)>=30ml/min;
7.Patients must be able to understand and willing to participate in the study and sign an informed consent form;

排除标准：

1.急性早幼粒细胞白血病；
2.合并中枢神经系统白血病；
3.确诊为髓系肉瘤；
4.接受过治疗的MDS/MPN/CMML患者进展为AML；
5.合并活动性感染，且研究者认为无法控制；
6.HBV-DNA或HCV-RNA阳性；
7.HIV感染；
8.心功能衰竭2级以上；
9.怀孕或哺乳的患者；
10.拒绝入组该研究患者；
11.其他研究者认为不适合入组的患者；

Exclusion criteria：

1.Acute promyelocytic leukemia;
2.With central nervous system leukemia;
3.Myeloid sarcoma;
4.secondary to treated MDS， MPN or CMML;
5.Uncontrollable active infection;
6.Positive for HBV-DNA or HCV-RNA;
7.HIV infection;
8.Heart failure grade 2 or higher;
9.Pregnant or nursing patients;
10.Patients who refused to enroll in the study;
11.Patients deemed unsuitable for enrollment by the investigators;

研究实施时间：

Study execute time：

从 From 2025-01-01 00:00:00至 To 2027-12-31 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2025-03-15 00:00:00 至 To 2026-12-31 00:00:00

干预措施：

Interventions：

组别：

GVA治疗组

样本量：

 32

Group：

GVA group

Sample size：

干预措施：

VA联合吉瑞替尼方案

干预措施代码：

Intervention：

VA combined with Gilteritinib regimen

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 江西 

市(区县)：

  

Country：

China

Province：

Jiangxi

City：

单位(医院)：

 南昌大学第一附属医院 

单位级别：

 三级甲等 

Institution
hospital：

The first affiliated hostipal of nanchang university

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

复合完全缓解率

指标类型：

主要指标

Outcome：

composite complete remission

Type：

Primary indicator

测量时间点：

诱导治疗结束后

测量方法：

骨髓细胞学

Measure time point of outcome：

After induction therapy

Measure method：

Bone marrow cytology

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：

研究结束时；治疗结束后每3个月

测量方法：

Kaplan-Meier生存曲线

Measure time point of outcome：

At the end of study；every three months after the end of treatment

Measure method：

Kaplan-Meier survival curve

指标中文名：

缓解深度

指标类型：

次要指标

Outcome：

remission depth

Type：

Secondary indicator

测量时间点：

下一疗程治疗开始前；治疗结束后每3个月

测量方法：

流式细胞术检测MRD，PCR法检测NPM1和FLT3/ITD定量

Measure time point of outcome：

Before the next course of treatment begins;every three months after the end of treatment

Measure method：

MRD detected by flow cytometry; NPM1 and FLT3/ITD quantified by PCR

指标中文名：

无复发生存期

指标类型：

次要指标

Outcome：

relapse-free survival

Type：

Secondary indicator

测量时间点：

研究结束时；治疗结束后每3个月

测量方法：

Kaplan-Meier生存曲线

Measure time point of outcome：

At the end of study；every three months after the end of treatment

Measure method：

Kaplan-Meier survival curve

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：

骨髓液

组织：

Sample Name：

bone marrow fluid

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：

尚未开始

Not yet recruiting

年龄范围：

Participant age：
最小 Min age 18 岁 years
最大 Max age 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）：

无

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

None

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

不公开/Private

盲法：

无

Blinding：

None

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）：

研究成果发表后，通过邮件向研究者索取原始数据。

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

After the results are published, ask the researchers for raw data by email.

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：

1.数据记录 本研究将采用电子病例报告表（eCRF）进行研究数据的采集与管理。 研究者必须保留所有的研究记录和原始文件，保留的时间应该尽量长，应为相关法规和指南或研究单位规程所要求的最长时间，或者是申办方所规定的时间，以最长者为准。在销毁与研究有关的任何记录之前，研究者都必须先联合申办方。 如果研究者退出了研究（如职位变化、退休等），则记录应移交给相关都认可的指定人员（如另外一位研究者）。对于这样的移交，必须书面通知申办方。（1）eCRF的填写 使用EDC采集临床研究数据。 可在eCRF上电子签名的每一个人都必须满足申办方的培训要求，而且只能使用申办方提供的，其本人专用的用户账号登陆电子数据采集系统。用户账号不得与他人共用，也不得再指定给其他人员。 填写：eCRF中的数据来自于原始病历和实验室检查报告单等原始文件并应与原始文件一致。试验中的任何观察、检查结果均应及时、正确、完整、清晰、规范、真实地填写于eCRF中，不得随意更改。CRF中的所有项目均需填写，不得空项或漏项。修改：如有需要，eCRF作数据更正时，需按照系统提示，填写数据修改的原因。系统逻辑核查程序将对录入到EDC系统中的数据进行临床试验数据的完整性和逻辑性检查，并对问题数据产生错误信息提示，允许研究者或数据录入人员（CRC）对问题数据进行修改或解释，必要时可以多次发出质疑直至问题数据解决。实验室检查：研究者应依据随访时间窗进行各项检查，采集、录入和报告受试者信息和数据，而且实验室检查报告单据作为原始文件之一应齐全，检查结果应及时录入至eCRF中。此外，原始数据还包括：自动化仪器记录或生成的数据的原始打印、照相底片、X光片、心电图记录、受试者日志卡等。此类文件都必须至少表明受试者编号和实施操作的日期。如有可能，对于这些记录的医学评价应该有必要的文件记录，文件由研究者签署姓名和日期。这些原始文件中的信息都应该及时录入eCRF中。（2）CRF的审核 研究者及其指定人员应及时完成eCRF的填写、审核并提交。研究者或数据录入人员（CRC）应及时回复来自监查员、数据管理员以及医学审核人员的质疑。在数据清理完成后，研究者对填写完毕的eCRF签名确认。（3）数据监查和稽查 必须允许申办方的授权代表（如监查员、稽查员等）定期拜访所有研究中心场所，评价数据的质量以及研究是否完整、可靠。他们将现场审核研究记录，将这些记录与原始文件直接比对，与研究者讨论研究的实施情况，确认研究设施是否仍符合要求。监查内容：是否遵循试验方案；所有CRF填写是否正确、完整，且与研究病历和实验室检查报告单等原始文件是否一致，数据有无错误或遗漏等。监查员将按照监查计划，对临床数据库中的试验数据进行完整性、一致性和准确性审查，并与研究人员对问题数据进行讨论，必要时研究人员进行补充或更正。确保eCRF中的数据与原始数据的一致性，该过程也被称为原始数据核查（SDV）。此外，政府部门的检查人员也可能会对研究进行评价，必须允许这些人员查阅eCRF、原始文件和其他研究文件，也必须允许他们检查研究设施。稽查报告必须保密。如果政府部门计划进行检查，研究者必须立即通知申办方，并迅速将检查报告提供给申办方 2.数据管理 （1）建立EDC数据库 数据管理员按照研究方案建立研究数据采集系统及数据库，并在第1例受试者入组前提供上线使用。使用前，所有EDC用户需得到所需的培训并获得登陆系统的相应账号（研究机构人员接受过培训后，才能登陆EDC系统）。（2）数据录入与核查 研究者或临床协调员（CRC）应按照访视流程的要求以及eCRF填写指南将数据输入EDC系统中。提交eCRF后，监查员、数据管理员以及医学人员应对数据进行逐一审核，审核中的问题以质疑的形式要求研究者或CRC回答。清理完毕后，eCRF需研究者签字确认。（3）数据库锁定 临床试验完成后，由研究负责人、申办者、统计专家和数据管理员共同进行统计分析前的审核，其重要内容就是确定每个病例归属的分析数据集、缺失值的判断及离群值的处理等。 经审核认为所建立的数据库正确无误后，对数据库进行锁定。数据库锁定后的数据需妥善保存备查，数据库交统计专家进行统计分析。 在CRA的SDV完结之后，数据管理人员和医学人员将对数据库的全部数据进行最后的质量控制，汇总试验进行中出现的所有方案偏移和方案违背的事件，召开数据核查会。数据库中的数据达到质量要求后，将进行数据库的锁定，数据管理人员将导出数据供统计部门进行数据分析。

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

1. Data Recording In this study, electronic Case Report Forms (eCRFs) will be used for the collection and management of research data. Researchers must retain all research records and original documents for as long as possible, following the requirements of relevant regulations, guidelines, institutional protocols, or the sponsor's specified duration, whichever is longer. Before destroying any records related to the study, researchers must consult with the sponsor. If a researcher withdraws from the study (e.g., due to job changes, retirement, etc.), the records should be transferred to a designated person recognized by the relevant authorities, such as another researcher. Written notification must be provided to the sponsor regarding such transfer. (1) eCRF Completion Clinical research data will be collected using an Electronic Data Capture (EDC) system. Every person who can electronically sign the eCRF must meet the training requirements set by the sponsor and can only log in to the electronic data capture system using their own dedicated user account provided by the sponsor. User accounts should not be shared with others or assigned to other personnel. Completion: Data in the eCRF should be derived from original medical records, laboratory reports, and other source documents, and should match the information in the original documents. Any observations or examination results in the study should be promptly, accurately, completely, clearly, consistently, and truthfully recorded in the eCRF without arbitrary changes. All items in the CRF must be completed, with no empty or missing fields. Modifications: If necessary, when making corrections to the eCRF, the reasons for the data modifications should be filled in according to system prompts. The system's logic checks will verify the integrity and consistency of the clinical trial data entered into the EDC system and provide error messages for problematic data. Researchers or data entry personnel (CRC) can modify or explain the data in question, and challenge it as many times as necessary until the data in question is resolved. Laboratory examination: The investigator shall conduct various examinations according to the follow-up time window, collect, input and report the subject information and data, and the laboratory examination report documents shall be complete as one of the original documents, and the examination results shall be recorded into the eCRF in time. In addition, raw data includes: original prints of data recorded or generated by automated instruments, photographic plates, X-rays, electrocardiogram records, subject log cards, etc. Such documents must indicate at least the subject number and the date the procedure was performed. If possible, the medical evaluation of these records should be accompanied by the necessary documentation, signed and dated by the investigator. The information in these original files should be entered into the eCRF in a timely manner. (2) CRF audit The investigator and his designee shall complete, review and submit the eCRF in a timely manner. The investigator or data entry officer (CRC) should respond promptly to queries from monitors, data managers, and medical reviewers. After the data cleaning was completed, the researcher confirmed the completed eCRF signature. (3) Data monitoring and auditing Authorized representatives of the sponsor (such as monitors, inspectors, etc.) must be allowed to visit all research center sites on a regular basis to evaluate the quality of the data and the completeness and reliability of the studies. They will review the study records on-site, compare them directly to the original documents, discuss the conduct of the study with the investigator, and confirm whether the research facility is still in compliance. Content of inspection: whether the test plan is followed; Whether all CRFS were filled in correctly and completely, and whether they were consistent with original documents such as study medical records and laboratory examination reports, and whether there were any errors or omissions in the data. According to the monitoring plan, the monitor will review the trial data in the clinical database for completeness, consistency and accuracy, and discuss the problem data with the researcher, and the researcher will supplement or correct it if necessary. To ensure that the data in the eCRF is consistent with the original data, this process is also known as the original data verification (SDV). In addition, research may also be evaluated by government inspectors, who must be allowed access to eCRF, original documents and other research documents and must be allowed to inspect research facilities. Audit reports must be kept confidential. If a government department plans to conduct an inspection, the investigator must immediately notify the sponsor and promptly provide the inspection report to the sponsor. 2. Data management (1) Establish EDC database The data manager established the research data acquisition system and database according to the study plan, and provided it for online use before the first subject was enrolled. Before use, all EDC users need to get the required training and obtain the corresponding login account (research institute personnel have been trained before they can log in to the EDC system). (2) Data entry and verification The investigator or clinical Coordinator (CRC) should enter data into the EDC system in accordance with the requirements of the visit procedure and the eCRF filling guidelines. After the eCRF is submitted, the auditor, data manager, and medical staff should review the data on a case-by-case basis and ask the investigator or CRC to answer the questions in the form of a challenge. After cleaning, the eCRF needs to be signed by the investigator. (3) The database is locked After the completion of the clinical trial, the head of the study, the sponsor, the statistical expert and the data manager jointly conducted the review before statistical analysis, the important content of which was to determine the analytical data set belonging to each case, the judgment of missing values and the treatment of outliers. After audit, it is found that the established database is correct, and the database is locked. After the database is locked, the data should be properly stored for future reference, and the database should be submitted to statistical experts for statistical analysis. After the completion of the SDV of CRA, the data manager and medical staff will conduct the final quality control of all the data in the database, summarize all the events of protocol deviation and protocol violation during the trial, and hold a data verification meeting. After the data in the database meets the quality requirements, the database will be locked, and the data manager will export the data for the statistical department to analyze.

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2025-03-11 10:02:14