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：	ChiCTR2300076685
最近更新日期： Date of Last Refreshed on：	2024-04-03 16:09:09
注册时间： Date of Registration：	2023-10-16 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	塞利尼索联合预激方案治疗维奈克拉耐药的复发难治AML和高危MDS有效性及安全性-多中心、单臂、前瞻性临床研究
Public title：	Efficacy and safety of serenixol combined with the priming regimen in the treatment of recurrent and refractory AML and high risk MDS with vineclavone resistance: a multicenter, single-arm, prospective clinical study
注册题目简写：
English Acronym：
研究课题的正式科学名称：	塞利尼索联合预激方案治疗维奈克拉耐药的复发难治AML和高危MDS有效性及安全性-多中心、单臂、前瞻性临床研究
Scientific title：	Efficacy and safety of serenixol combined with the priming regimen in the treatment of recurrent and refractory AML and high risk MDS with vineclavone resistance: a multicenter, single-arm, prospective clinical study
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：	韩洁	研究负责人：	郭子敬
Applicant：	Jie Han	Study leader：	Zijing Guo
申请注册联系人电话： Applicant telephone：	+86 186 5210 8339	研究负责人电话： Study leader's telephone：	+86 182 0322 3002
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：	hanj6@hspharm.com	研究负责人电子邮件： Study leader's E-mail：	drzaking@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：	河北省石家庄市和平西路215号	研究负责人通讯地址：	河北省石家庄市中山东路389号
Applicant address：	215 Heping Road West, Shijiazhuang, Hebei	Study leader's address：	389 Zhongshan Road East, Shijiazhuang, Hebei
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：	河北医科大学第二医院
Applicant's institution：	The Second Hospital of Hebei Medical University
研究负责人所在单位：	河北省中医院
Affiliation of the Leader：	Hebei Provincial Hospital of Traditional Chinese Medicine

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：	HBZY2023-KY-029-01	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：	河北省中医院医学伦理委员会
Name of the ethic committee：	Medical Ethics Committee of Hebei Provincial Hospital of Traditional Chinese Medicine
伦理委员会批准日期： Date of approved by ethic committee：	2023-08-10 00:00:00
伦理委员会联系人：	胡婧楠
Contact Name of the ethic committee：	Jingnan Hu
伦理委员会联系地址：	河北省石家庄市中山东路389号
Contact Address of the ethic committee：	389 Zhongshan Road East, Shijiazhuang, Hebei
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 311 6909 5606	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：

河北省中医院

Primary sponsor：

Hebei Provincial Hospital of Traditional Chinese Medicine

研究实施负责（组长）单位地址：

河北省石家庄市中山东路389号

Primary sponsor's address：

389 Zhongshan Road East, Shijiazhuang, Hebei

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：	中国	省(直辖市)：	河北	市(区县)：
Country：	China	Province：	Hebei	City：
单位(医院)：	河北省中医院	具体地址：	河北省石家庄市中山东路389号
Institution hospital：	Hebei Provincial Hospital of Traditional Chinese Medicine	Address：	389 Zhongshan Road East, Shijiazhuang, Hebei

经费或物资来源：

无

Source(s) of funding：

None

研究疾病：

骨髓增生异常综合征和急性髓性白血病

Target disease：

Myelodysplastic syndrome & Acute myeloid leukemia

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：

上市后药物

Study phase：

4

研究设计：

单臂

Study design：

Single arm

研究目的：

探索塞利尼索联合预激方案治疗维奈克拉耐药的复发难治AML和高危MDS有效性及安全性。

Objectives of Study：

To explore the efficacy and safety of serenixol combined with the priming regimen in the treatment of recurrent and refractory AML and high risk MDS with vineclavone resistance.

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.知晓本方案并自愿签署知情同意书；
2.年龄为≥18岁，性别不限；
3.符合世界卫生组织（WHO）2022造血和淋巴细胞组织肿瘤分类标准确诊的伴有原发性AML或骨髓增生异常综合征(MDS)；
4.初治患者不能耐受高强度化疗或不愿意接受高强度化疗的初诊AML患者或MDS；或经过一疗程标准诱导化疗（DA/IA 3+7 或者低强度化疗（维纳克拉+阿扎胞苷等）诱导治疗后出现难治或复发的AML或MDS；复发/难治的定义需符合以下任一条件：（1）复发：定义为“一线治疗达到CRMRD-、CR、CRi”后，外周血重新出现白血病细胞、或骨髓幼稚/原始细胞占骨髓细胞之比率≥5%；（2）难治：经标准方案诱导化疗至少1个疗程后未获“CR、Cri、CRh、MLFS”的原发性难治性疾病；不符合标准治疗条件的受试者，必须已完成研究者评估后选择的诱导缓解的最佳治疗，接受至少1个完整的诱导缓解治疗周期；
5.根据研究者判断，受试者疾病处于快速增殖状态，无法等待中心实验室的试验结果，则可以根据受试者末次干预性治疗结束后进行的当地实验室（为具有监管部门实验室资质认证的本院或外院或第三方检测机构）检测结果评估入组；
6.ECOG评分为0-2分；
7.预期生存时间≥12周；
8.经研究者评估，受试者适合接受试验方案选定的挽救性化疗；
9.受试者必须有适当的器官功能，入组前符合下列所有实验室检查结果：
（1）凝血功能：国际标准化比值（INR）<1.5 × ULN（无正常值参考范围时，则INR <1.8）和活化部分凝血活酶时间（APTT）1.5 × ULN；
（2）电解质：血钾≥3.0 mmol/L；血镁≥0.5 mmol/L；
（3）肝功能：ALT和AST ≤2.5× ULN；血清胆红素≤1.5× ULN；
（4）肾功能：血清肌酐≤1.5× ULN；或根据Cockcroft-Gault公式计算的肌酐清除率（Ccr）>50 mL/min；
10.受试者须愿意提供治疗前已有的有效诊断证据或接受骨髓检查，和在治疗后 接受骨髓检查；
11.非哺乳期女性受试者；对有生育能力的女性受试者：筛选期血妊娠检查必须为妊娠阴性，在签署知情同意书至研究治疗末次用药后6个月内无试管取卵计划且同意采取高效避孕措施。未绝育的男性受试者：在签署知情同意书至研究治疗末次用药后6个月内无捐献精子计划且同意采取高效避孕措施；
12.受试者自愿参加本研究，并由本人或监护人或公正见证人（如适用）签署了书面知情同意书；
13.受试者或其监护人能够与研究者进行良好的沟通，且受试者愿意依照方案规定完成试验。

Inclusion criteria

1. Be aware of this plan and voluntarily sign an informed consent form;
2. Aged >= 18 years old, regardless of gender;
3. Confirmed cases with primary AML or myelodysplastic syndrome (MDS) that meet the World Health Organization (WHO) 2022 classification criteria for hematopoietic and lymphocytic tissue tumors;
4. Newly diagnosed AML patients or MDS who are unable to tolerate or unwilling to undergo high-intensity chemotherapy; Or, after a course of standard induction chemotherapy (DA/IA 3+7 or low-intensity chemotherapy (Venacra+azacitidine, etc.) induction treatment, refractory or recurrent AML or MDS may occur; The definition of recurrence/refractory needs to meet any of the following conditions: (1) Recurrence: defined as the reappearance of leukemia cells in peripheral blood or the proportion of bone marrow immature/primitive cells to bone marrow cells >= 5% after the first-line treatment reaches CRMRD -, CR, CRi; (2) Refractory: Primary refractory diseases that have not achieved "CR, Cri, CRh, MLFS" after at least one course of standard regimen induced chemotherapy; Subjects who do not meet the standard treatment conditions must have completed the optimal treatment for induced remission selected by the researcher after evaluation, and receive at least one complete treatment cycle for induced remission;
5. According to the judgment of the researcher, if the subject's disease is in a rapidly proliferating state and cannot wait for the test results of the central laboratory, the inclusion can be evaluated based on the test results of the local laboratory (which is a local or external hospital or third-party testing institution with regulatory laboratory qualification certification) conducted after the end of the subject's last intervention treatment;
6. The ECOG score is 0-2 points;
7. Expected survival time >= 12 weeks;
8. After evaluation by the researchers, the subjects are suitable for receiving salvage chemotherapy selected by the experimental protocol;
9. The subjects must have appropriate organ function and meet all the following laboratory test results before enrollment:
(1) Coagulation function: International standardized ratio (INR) < 1.5 × ULN (INR < 1.8 when there is no normal reference range) and activated partial thromboplastin time (APTT) 1.5 × ULN;
(2) Electrolyte: Blood potassium >= 3.0 mmol/L; Blood magnesium >= 0.5 mmol/L;
(3) Liver function: ALT and AST <= 2.5 × ULN; Serum bilirubin <= 1.5 × ULN;
(4) Renal function: serum creatinine <= 1.5 × ULN; Alternatively, the creatinine clearance rate (Ccr) calculated according to the Cockcroft Fault formula is greater than 50 mL/min;
10. The subjects must be willing to provide valid diagnostic evidence prior to treatment or undergo bone marrow examination, as well as undergo bone marrow examination after treatment;
11. Non lactating female subjects; For female subjects with fertility: During the screening period, the blood pregnancy test must be negative for pregnancy, and there is no IVF plan within 6 months after signing the informed consent form and the last medication used in the research treatment, and they agree to adopt efficient contraceptive measures. Unsterilized male subjects: Within 6 months after signing the informed consent form and taking the last medication for the study treatment, there was no plan to donate sperm and they agreed to adopt efficient contraceptive measures;
12. The subjects voluntarily participated in this study and were personally;
13. The subjects or their guardians are able to communicate well with the researchers, and the subjects are willing to complete the experiment according to the protocol.

排除标准：

1. 既往接受过塞列尼索者； 2. 随机前2个月内接受过造血干细胞移植，或者筛选期内在造血干细胞移植后因移植物抗宿主病而接受抗GVHD治疗的急慢性GVHD受试者； 3. 随机前4周或≤5×药物半衰期（若明确药物的半衰期则按5倍半衰期算，否则为4周）之内接受过化疗、靶向治疗、抗肿瘤免疫治疗（免疫检查点抑制剂、CAR-T治疗等）、放疗、重大手术（不包括诊断性手术）治疗的受试者； 4. 随机前4周内接受活疫苗（包括减毒活疫苗）和/或计划入组后接受活疫苗者； 5. 随机前4周内参加过任何干预性临床试验并接受了试验药物或医疗器械干预（参与一项研究的总生存期随访受试者除外）； 6. 诊断为急性早幼粒细胞白血病的受试者； 7. 受试者患有BCR-ABL阳性白血病（慢性粒细胞白血病急变）； 8. 随机前5年内合并除AML外的其他恶性肿瘤，不包括：转移或死亡风险可忽略不计（如预期5年OS > 90%）且经治疗后预期可治愈的肿瘤（如宫颈原位癌、皮肤基底细胞癌或鳞状细胞癌、接受根治性手术治疗的局限性前列腺癌、根治性手术治疗的乳腺导管原位癌等），或任何已治愈（5年内无疾病复发的证据）的其他肿瘤。

Exclusion criteria：

1. Those who have previously received Serenisos; 2. Acute and chronic GVHD subjects who have received hematopoietic stem cell transplantation within the first 2 months of randomization, or who have received anti GVHD treatment for graft versus host disease after hematopoietic stem cell transplantation during the screening period; 3. Before randomization, 4 weeks or <= 5 × Subjects who have received chemotherapy, targeted therapy, anti-tumor immunotherapy (immune checkpoint inhibitors, CAR-T therapy, etc.), radiotherapy, or major surgery (excluding diagnostic surgery) within the half-life of the drug (if the half-life of the drug is specified, it is calculated as 5 times the half-life, otherwise it is 4 weeks); 4. Those who receive live vaccines (including attenuated live vaccines) within the first 4 weeks of randomization and/or plan to receive live vaccines after enrollment; 5. Participated in any intervention clinical trial and received intervention with investigational drugs or medical devices within the first 4 weeks of randomization (excluding participants in a study with overall survival follow-up); 6. Subjects diagnosed with acute promyelocytic leukemia; 7. The subject has BCR-ABL positive leukemia (chronic myeloid leukemia); 8. Malignant tumors other than AML that have merged within the first 5 years of randomization, excluding tumors that have a negligible risk of metastasis or death (if the expected 5-year OS is > 90%) and are expected to be curable after treatment (such as cervical carcinoma in situ, skin basal cell carcinoma or squamous cell carcinoma, localized prostate cancer undergoing radical hand surgery, breast ductal carcinoma in situ undergoing radical surgery, etc.), Or any other tumor that has been cured (with no evidence of disease recurrence within 5 years).

研究实施时间：

Study execute time：

从 From 2023-10-16 00:00:00至 To 2025-10-15 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2023-10-16 00:00:00 至 To 2025-10-15 00:00:00

干预措施：

Interventions：

组别：	治疗组	样本量：	96
Group：	Treatment group	Sample size：	96
干预措施：	塞利尼索、地西他滨、阿糖胞苷、阿克拉霉素、高三尖杉酯碱、去甲氧基柔红霉素、粒细胞集落刺激因子	干预措施代码：
Intervention：	Serenixol, Dexcitabine, Cytarabine, Aclamycin, Homoharringtonine, Demethoxydaunorubicin, Granulocyte colony stimulating factor	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	河北	市(区县)：
Country：	China	Province：	Hebei	City：
单位(医院)：	河北省中医院	单位级别：	三甲
Institution hospital：	Hebei Provincial Hospital of Traditional Chinese Medicine	Level of the institution：	Tertiary A

国家：	中国	省(直辖市)：	河北	市(区县)：
Country：	China	Province：	Hebei	City：
单位(医院)：	河北医科大学第四医院	单位级别：	三甲
Institution hospital：	The Fourth Hospital of Hebei Medical University	Level of the institution：	Tertiary A

国家：	中国	省(直辖市)：	河北	市(区县)：
Country：	China	Province：	Hebei	City：
单位(医院)：	河北医科大学第二医院	单位级别：	三甲
Institution hospital：	The Second Hospital of Hebei Medical University	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	完全缓解率	指标类型：	主要指标
Outcome：	Complete response rate, CR	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	客观缓解率	指标类型：	次要指标
Outcome：	Objective response rate, ORR	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	安全性和耐受性	指标类型：	次要指标
Outcome：	Safety and tolerability	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：	NA	组织：
Sample Name：	NA	Tissue：
人体标本去向	其它	说明
Fate of sample：	0thers	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	100	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:

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	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）：	NA
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	NA
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：	病历记录表
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：	暂未确定/Not yet
注册人： Name of Registration：	2023-10-16 11:44:57