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：	ChiCTR2400094549
最近更新日期： Date of Last Refreshed on：	2024-12-24 16:12:00
注册时间： Date of Registration：	2024-12-24 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	盐酸米托蒽醌脂质体注射液联合苯达莫司汀、依托泊苷、阿糖胞苷用于淋巴瘤患者自体造血干细胞移植预处理的临床研究
Public title：	Clinical study of Mitoxantrone hydrochloride liposome injection combined with bendamustine, etoposide and cytarabine for the preconditioning of autologous hematopoietic stem cell transplantation in patients with lymphoma
注册题目简写：
English Acronym：
研究课题的正式科学名称：	盐酸米托蒽醌脂质体注射液联合苯达莫司汀、依托泊苷、阿糖胞苷用于淋巴瘤患者自体造血干细胞移植预处理的临床研究
Scientific title：	Clinical study of Mitoxantrone hydrochloride liposome injection combined with bendamustine, etoposide and cytarabine for the preconditioning of autologous hematopoietic stem cell transplantation in patients with 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：	欧阳桂芳	研究负责人：	欧阳桂芳
Applicant：	Guifang Ouyang	Study leader：	Guifang Ouyang
申请注册联系人电话： Applicant telephone：	+86 13967810405	研究负责人电话： Study leader's telephone：	+86 574 87085111
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：	nbhematology@163.com	研究负责人电子邮件： Study leader's E-mail：	nbougf@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：	宁波市海曙区柳汀街宁波大学附属第一医院血液科	研究负责人通讯地址：	浙江省宁波市海曙区柳汀街59号
Applicant address：	Department of Hematology, the First Affiliated Hospital of Ningbo University, Liuting Street, Ningbo	Study leader's address：	Liuting street NO.59,haishu district, ningbo city, zhejiang provience
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：	宁波大学附属第一医院
Applicant's institution：	The First Affiliated Hospital of Ningbo University
研究负责人所在单位：	宁波大学附属第一医院
Affiliation of the Leader：	The First Affiliated Hospital of Ningbo 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：	宁波大学附属第一医院伦审2024研第157A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：	宁波大学附属第一医院医学伦理委员会
Name of the ethic committee：	Medical Ethics Committee of the First Affiliated Hospital of Ningbo University
伦理委员会批准日期： Date of approved by ethic committee：	2024-12-12 00:00:00
伦理委员会联系人：	陈少莹
Contact Name of the ethic committee：	Shaoying Chen
伦理委员会联系地址：	浙江省宁波市海曙区柳汀街59号
Contact Address of the ethic committee：	No. 59, Liuting Street, Haishu District, Ningbo City, Zhejiang Province
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 574 87085233	伦理委员会联系人邮箱： Contact email of the ethic committee：	sychenjy@163.com

研究实施负责（组长）单位：

宁波大学附属第一医院

Primary sponsor：

The First Affiliated Hospital of Ningbo University

研究实施负责（组长）单位地址：

浙江省宁波市海曙区柳汀街59号

Primary sponsor's address：

Liuting street NO.59,haishu district, ningbo city, zhejiang provience

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：	中国	省(直辖市)：	浙江	市(区县)：
Country：	China	Province：	Zhejiang	City：
单位(医院)：	宁波大学附属第一医院	具体地址：	浙江省宁波市海曙区柳汀街59号
Institution hospital：	Ningbo First Hospital	Address：	liuting street NO.59,haishu district, ningbo city, zhejiang provience

经费或物资来源：

石药集团中诺药业（石家庄）有限公司

Source(s) of funding：

Shiyao Group Zhongnuo Pharmaceutical (Shijiazhuang) Co., LTD

研究疾病：

非霍奇金淋巴瘤

Target disease：

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：

其它

Study phase：

N/A

研究设计：

单臂

Study design：

Single arm

研究目的：

1. 主要目的：评估盐酸米托蒽醌脂质体注射液联合苯达莫司汀、依托泊苷、阿糖胞苷用于NHL患者自体造血干细胞移植预处理的安全性。 2. 次要目的：评估盐酸米托蒽醌脂质体注射液联合苯达莫司汀、依托泊苷、阿糖胞苷用于NHL患者自体造血干细胞移植预处理的有效性。

Objectives of Study：

1. Main Objective: To evaluate the safety of mitoxantrone hydrochloride liposome injection combined with bendamustine, etoposide and cytarabine for preconditioning autologous hematopoietic stem cell transplantation in NHL patients. 2. Secondary objective: To evaluate the efficacy of mitoxantrone hydrochloride liposome injection combined with bendamustine, etoposide and cytarabine for preconditioning autologous hematopoietic stem cell transplantation in NHL 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：

Inclusion criteria

1. Patients voluntarily join the study, sign the informed consent form, have good compliance, and cooperate with follow-up;
2. Patients with non-Hodgkin lymphoma or malignant lymphoma confirmed by histology or pathology, aged 18~75 years old (including the upper limit), regardless of gender, are planned to undergo autologous hematopoietic stem cell transplantation;
3. Eastern Cooperative Oncology Group (ECOG) physical condition: score of 0~2 points, expected survival of more than 3 months;
4. Patients judged by the investigator to be suitable for stem cell transplantation: consolidation therapy after first-line induction chemotherapy for aggressive non-Hodgkin lymphoma with poor prognostic factors; It is suitable for salvage therapy for chemotherapy-sensitive non-Hodgkin lymphoma after recurrence; and salvage therapy for chemotherapy-sensitive, relapsed or primary-refractory Hodgkin lymphoma.
5. The function of major organs is normal, and the specific criteria are as follows: bone marrow hematopoietic function is basically normal, blood routine: WBC > = 2.0×10^9/L, ANC ≥ 1.0×10^9/L, PLT > = 50×10^9/L, Hb > = 80 g/L. If the peripheral blood index is abnormal due to lymphoma invasion of bone marrow or spleen, it can be judged by the investigator at the discretion of whether it is suitable for enrollment; Pulmonary function: forced expiratory volume in one second (FEV1) > = 60%, diffusing capacity for carbon monoxide (DLCO) > = 50%; Liver function: total bilirubin, ALT and AST < 2× ULN (upper limit of normal); AST, ALT < = 3 times the upper limit of normal (ULN), total bilirubin (TBIL) < = 1.5× ULN (AST, ALT < = 5 ×ULN are allowed if there is hepatic invasion); Renal function: serum creatinine < = 1.5× ULN, creatinine clearance (CrCl) > = 60 ml/min (calculated according to the Cockcroft-Gault formula). Male subjects: CLcr = [(140-age (years)× body weight (kg))/[72× serum creatinine (mg/dL)]]; Female subjects: CLcr=0.85× CLcr for male subjects; Coagulation function: International normalized ratio (INR) and activated partial thromboplastin time (APTT) <=1.5×ULN; Normal cardiac function: echocardiography or nuclear cardiac function tests, LVEF > = 55%, no uncontrolled tachycardia or tachy-bradycardia, normal or abnormal ECG not clinically significant, normal cardiac enzyme spectrum CK-MB, pro-BNP less than 900 pg/ml.
6. Sufficient autologous hematopoietic stem cells have been judged and collected by the investigator: CD34>=2×106/kg;
7. Female not lactating, non-pregnant, female subjects of reproductive potential with a negative serum pregnancy test within 2 weeks prior to enrollment, and agree not to become pregnant during the period of enrollment and for 36 months thereafter; Male or female subjects of reproductive potential must use a highly effective method of contraception throughout the trial and for 1 year after transplantation.

排除标准：

1. 既往接受过阿霉素或其他蒽环类治疗，总累积剂量阿霉素＞360 mg/m²（其它蒽环类药物换算1 mg阿霉素相当于2 mg表柔比星）。 2. 对任何研究药物或其成分有超敏反应。 3. 心脏功能和疾病符合下述情况之一： a. 长QTc综合征或QTc间期>480 ms； b. 完全性左束支传导阻滞，II度或III度房室传导阻滞； c. 需要药物治疗的严重、未控制的心律失常； d. 美国纽约心脏病学会分级>= III级； e. 心脏射血分数（LVEF）低于50%； f. 在招募前6个月内出现心肌梗死、不稳定心绞痛、严重不稳定室性心律失常病史或其他任何需要治疗的心律失常、临床严重的心包疾病病史，或有急性缺血性或活动性传导系异常的心电图证据。 4. 乙肝、丙肝活动期感染（乙肝病毒表面抗原或核心抗体阳性且乙肝病毒DNA超过1×10³拷贝/mL；丙肝病毒RNA超过1×10³拷贝/mL）。 5. 人类免疫缺陷病毒（HIV）感染（HIV抗体阳性）。 6. 既往或现在同时患有其他恶性肿瘤（以下情况除外：已经接受过以治愈为目的的治疗，且入组前>=5年未发生过已知活动性疾病的恶性肿瘤；接受过充分治疗，没有患病迹象的皮肤基底细胞癌（除黑色素瘤）；接受过充分治疗，没有患病迹象的宫颈原位癌）。 7. 患有原发性或继发性中枢神经系统（CNS）淋巴瘤或具有CNS淋巴瘤病史。 8. 妊娠、哺乳期女性和不愿采取避孕措施的育龄患者。 9. 无法收集数量大于或等于2×10^6/kg的CD34 +造血干细胞的患者。 10. 以往接受过实体器官移植的患者。 11. 治疗前三周内接受过二级及以上的手术者。 12. 移植前15天内存在需要全身抗生素、抗真菌药物、抗病毒治疗的严重活动性感染性疾病。 13. 有药物（非医疗目的使用麻醉药品或精神药品）滥用史或药物（镇静催眠药、镇痛药、麻醉药、兴奋药及拟精神病性药物等）依赖史者。 14. 有严重的神经或精神病史，包括痴呆或癫痫。 15. 精神疾病病史或认知障碍病史。 16. 研究者认为不适合入组的患者。

Exclusion criteria：

1. Prior treatment with doxorubicin or other anthracyclines, with a total cumulative dose of doxorubicin > 360 mg/m² (1 mg of doxorubicin is equivalent to 2 mg of epirubicin for other anthracyclines). 2. Hypersensitivity to any of the study drugs or their components. 3. Cardiac function and disease consistent with one of the following: a. Long QTc syndrome or QTc interval >480 ms; b. Complete left bundle branch block, second- or third-degree atrioventricular block; c. Severe, uncontrolled cardiac arrhythmias requiring medication; d. New York College of Cardiology grade > = Class III; Cardiac ejection fraction (LVEF) less than 50%; f. History of myocardial infarction, unstable angina, severe unstable ventricular arrhythmia or any other arrhythmia requiring treatment, history of clinically severe pericardial disease, or ECG evidence of acute ischemic or active conduction abnormalities within 6 months prior to recruitment. 4. Active hepatitis B and hepatitis C infection (positive for hepatitis B virus surface antigen or core antibody and hepatitis B virus DNA more than 1×10³ copies/mL; HCV RNA > 1×10³ copies/mL). 5. Human immunodeficiency virus (HIV) infection (HIV antibody positive). 6. Previous or present concomitant other malignant tumors (except for the following circumstances: malignant tumors that have received treatment with curative intent and have not had known active disease in the > = 5 years prior to enrollment; Basal cell carcinoma of the skin (except melanoma) that has been adequately treated and has no signs of disease; Carcinoma in situ of the cervix that has been adequately treated and has no signs of disease). 7. Have primary or secondary central nervous system (CNS) lymphoma or have a history of CNS lymphoma. 8. Pregnant, lactating females and patients of childbearing age who are unwilling to use contraception. 9. Patients who are unable to collect CD34+ hematopoietic stem cells in quantities greater than or equal to 2×10^6/kg. 10. Patients who have received solid organ transplantation in the past. 11. Those who have undergone secondary surgery or above within three weeks before treatment. 12. Presence of severe active infectious disease requiring systemic antibiotics, antifungal drugs, antiviral therapy within 15 days prior to transplantation. 13. Those who have a history of drug abuse (use of narcotic drugs or psychotropic substances for non-medical purposes) or drug dependence (sedative-hypnotics, analgesics, narcotics, stimulants and psychotic drugs, etc.). 14. Has a history of severe neurological or psychiatric illness, including dementia or epilepsy. 15. History of psychiatric illness or cognitive impairment. 16. Patients who, in the opinion of the investigator, are not suitable for enrollment.

研究实施时间：

Study execute time：

从 From 2024-11-01 00:00:00至 To 2027-12-31 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2025-01-01 00:00:00 至 To 2026-06-30 00:00:00

干预措施：

Interventions：

组别：	试验组	样本量：	30
Group：	Experimental group	Sample size：	30
干预措施：	苯达莫司汀+阿糖胞苷+依托泊苷+米托蒽醌脂质体	干预措施代码：
Intervention：	Bendamustine + cytarabine + etoposide + mitoxantrone liposomes	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	浙江	市(区县)：
Country：	China	Province：	Zhejiang	City：
单位(医院)：	宁波大学附属第一医院	单位级别：	三级甲等
Institution hospital：	Ningbo First Hospital	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	造血重建标准	指标类型：	次要指标
Outcome：	Hematopoietic reconstruction criteria	Type：	Secondary indicator
测量时间点：	粒细胞植入时间：停用G-CSF后，中性粒细胞绝对计数（ANC）>0.5×109/L连续3 d的第1天；血小板植入时间：当脱离输注血小板时，PLT>20×109/L连续7 d的第1天。	测量方法：	测量尺度
Measure time point of outcome：	Granulocyte implantation time: After G-CSF was stopped, the absolute count of neutrophils (ANC) was	Measure method：	Measurement scale

指标中文名：	预处理相关不良反应评价、移植相关死亡率	指标类型：	主要指标
Outcome：	Evaluation of pretreatment-related adverse reactions and transplant-related mortality	Type：	Primary indicator
测量时间点：	100天	测量方法：	测量尺度
Measure time point of outcome：	Day100	Measure method：	Measurement scale

指标中文名：	疗效评估和随访	指标类型：	次要指标
Outcome：	Efficacy evaluation and follow-up	Type：	Secondary indicator
测量时间点：	总生存（OS）时间：从移植开始到死亡或末次随访时间（时间范围：移植后6个月、12个月、18个月、24个月、30个月、36个月）无进展生存（PFS）时间：从移植开始到疾病进展、复发、死亡或末次随访时间	测量方法：	测量尺度
Measure time point of outcome：	Overall survival (OS) time: from transplant initiation to death or last follow-up (time range: 6 mon	Measure method：	Measurement scale

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：

尚未开始

Not yet recruiting

年龄范围：

Participant age：

最小 Min age	18	岁 years
最大 Max age	75	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）：	无
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	None
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：	CRF;EDC
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	CRF;EDC
数据与安全监察委员会： Data and Safety Monitoring Committee：	有/Yes
注册人： Name of Registration：	2024-12-24 16:11:51