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：	ChiCTR2000033483
最近更新日期： Date of Last Refreshed on：	2020-06-02 18:33:09
注册时间： Date of Registration：	2020-06-02 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	来那度胺联合 CD20 单抗-CHOP 治疗初治双表达弥漫大 B 细胞淋巴瘤的开放性、多中心Ⅱ期临床研究
Public title：	Lenalidomide combined with Anti-CD20 monoclonal antibodies-CHOP in untreated Diffuse Large B-Cell Lymphoma patients with MYC and BCL2 co-expression: a open-lable, multicenter, phase II study
注册题目简写：
English Acronym：
研究课题的正式科学名称：	来那度胺联合 CD20 单抗-CHOP 治疗初治双表达弥漫大 B 细胞淋巴瘤的开放性、多中心Ⅱ期临床研究
Scientific title：	Lenalidomide combined with Anti-CD20 monoclonal antibodies-CHOP in untreated Diffuse Large B-Cell Lymphoma patients with MYC and BCL2 co-expression: a open-lable, multicenter, phase II 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：	王婷婷	研究负责人：	李志铭
Applicant：	Tingting Wang	Study leader：	Zhiming Li
申请注册联系人电话： Applicant telephone：	+86 18588897706	研究负责人电话： Study leader's telephone：	+86 18826437876
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：	1170952215@qq.com	研究负责人电子邮件： Study leader's E-mail：	sunp@sysucc.org.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：	广东省广州市番禺区大石街永信大楼201	研究负责人通讯地址：	广东省广州市越秀区东风东路651号
Applicant address：	Room 201, Yongxin Building, Dashi Street, Panyu District, Guangzhou, Guangdong, China	Study leader's address：	651 Dongfeng Road East, Yuexiu District, Guangzhou, Guangdong, 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：	中山大学肿瘤防治中心
Applicant's institution：	Cancer Prevention and Treatment Center, Sun Yat-Sen University
研究负责人所在单位：	中山大学肿瘤防治中心
Affiliation of the Leader：	Cancer Center of Sun Yat-Sen 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：	B2020-052-01	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：	中山大学肿瘤防治中心伦理委员会
Name of the ethic committee：	Ethics Committee of Cancer Prevention and Treatment Center, Sun Yat-Sen University
伦理委员会批准日期： Date of approved by ethic committee：	2020-05-27 00:00:00
伦理委员会联系人：	彭望清
Contact Name of the ethic committee：	Wangqing Peng
伦理委员会联系地址：	广东省广州市越秀区东风东路651号
Contact Address of the ethic committee：	651 Dongfeng Road East, Yuexiu District, Guangzhou, Guangdong, China
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：

中山大学肿瘤防治中心

Primary sponsor：

Cancer Prevention and Treatment Center, Sun Yat-Sen University

研究实施负责（组长）单位地址：

广东省广州市越秀区东风东路651号

Primary sponsor's address：

651 Dongfeng Road East, Yuexiu District, Guangzhou, Guangdong, 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)：	广东	市(区县)：	广州
Country：	China	Province：	Guangdong	City：	Guangzhou
单位(医院)：	中山大学肿瘤防治中心	具体地址：	越秀区东风东路651号
Institution hospital：	Cancer Prevention and Treatment Center, Sun Yat-Sen University	Address：	651 Dongfeng Road East, Yuexiu District

经费或物资来源：

研究者自筹

Source(s) of funding：

Self-raised funds

研究疾病：

弥漫大 B 细胞淋巴瘤

Target disease：

DLBCL

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：

探索来那度胺联合利妥昔单抗、长春新碱、阿霉素、环磷酰胺、泼尼松（R2-CHOP）治疗初治DEL-DLBCL 的有效性和安全性。

Objectives of Study：

To assess the efficacy and safety of lenalidomide combined with rituximab, vincristine, doxorubicin, cyclophosphamide and prednisone (r2-chop) in the initial treatment of DEL-DLBCL.

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. The double expression diffuse large B cell lymphoma was confirmed by histopathology. The positive rate of Bcl-2 and c-myc was more than 50% and 40% respectively;
2. Male or female patients: 18-80 years old;
3. Patients with ECoG physical condition score: 0-2 points;
4. Patients with IPI score >= 3;
5. Patients who have not received any anti-tumor treatment such as radiotherapy, chemotherapy, targeted therapy or stem cell transplantation;
6. There must be at least one patient with an evaluable or measurable lesion in accordance with Lugano 2014 standard [evaluable lesion: 18F fluorodeoxyglucose / positron emission tomography (18FDG / PET) examination showed an increased uptake of lymph nodes or extranodal areas (higher than liver) and pet and / or computed The features of tomography (CT) were in accordance with lymphoma; measurable lesions: nodal lesions > 15mm in length or extranodal lesions > 10 mm in length, accompanied by increased 18FDG uptake]. There was no measurable lesion and the uptake of 18FDG was increased.
7. The function of main organs is good, that is to say, the following requirements shall be met one week before admission: blood routine WBC >= 3.5 x 10^9 / L, neu >= 1.5 x 10^9 / L, Hb >= 80g / L, PLT >= 100 x 10^9 / L; the function of heart and liver is normal (total bilirubin <= 1.5 times of normal value, ALT and AST <= 2.5 times of normal value), renal function is normal (serum creatinine <= 1.5 times of normal value), and there is no coagulation function abnormality.
8. Patients with LVEF >= 50% measured by echocardiography.
9. Patients (including steroid drugs) without other anti-tumor concomitant treatment.
10. Pregnant women of childbearing age must carry out pregnancy test (serum or urine) within 14 days before entering the group, and the result is negative, and they are willing to use reliable methods of contraception during the test.
11. Patients without other serious diseases in conflict with the program.
12. The subjects volunteered to join the study, signed the informed consent, had good compliance and cooperated with the follow-up.

排除标准：

1. 其他类型 DLBCL：慢性炎症相关的 DLBCL、淋巴瘤样肉芽肿、原发纵隔大 B 细胞淋巴瘤、ALK 阳性大 B 细胞淋巴瘤、原发渗出性淋巴瘤、Burkitt 淋巴瘤、高级别 B 细胞淋巴瘤（包括高级别 B 细胞淋巴瘤，NOS 及伴有 MYC 和 BCL2 和/或 BCL6重排的高级别 B 细胞淋巴瘤）、B 细胞淋巴瘤不能分类（具有介于 DLBCL 和经典型霍奇金淋巴瘤中间特点）、原发性中枢神经系统（CNS）DLBCL，EBV（+）DLBCL。
2. 转化型 DLBCL（如滤泡性淋巴瘤、慢性淋巴细胞白血病/小 B 淋巴细胞淋巴瘤转化的 DLBCL），DLBCL 继发性中枢神经系统受侵。
3. 过去 5 年内有皮肤鳞状细胞癌、皮肤基底细胞癌、宫颈原位癌以外的其他恶性肿瘤病史。
4. 过去 2 个月内进行过大的外科手术（不包括诊断性外科手术）。
5. 曾经接受过 NHL 治疗：包括化疗、免疫治疗、放疗、单克隆抗体治疗、外科治疗（诊断性手术和活检除外）。
6. 既往接受过细胞毒药物或单抗 CD20 抗体治疗其他疾病（如类风湿关节炎）。
7. 既往接受过沙利度胺、来那度胺等药物治疗。
8. 入组前 3 个月内使用了任何单克隆抗体、参加过其它临床试验且使用了其它试验相关药物者、入组前 1 个月内曾接种（减毒）活病毒疫苗者。
9. 入组前 2 周内使用过造血细胞因子。
10. 疑似活动性或潜伏性结核患者。
11. 在入组前 4 周内已知有活动性细菌、病毒、真菌、分支杆菌、寄生虫感染或其他感染（不包括甲床皮肤真菌感染）或需要静脉抗生素治疗或住院的任何重大全身感染事件者（肿瘤性发热除外）。
12. 其他严重的可能限制受试者参加此试验的疾病，例如：不能控制的糖尿病；严重心功能不全（NYHA 分级 II 级以上）；近 6 个月内出现急性冠脉综合征；近 6月内冠脉血运重建如支架植入术、冠脉搭桥手术、以及其他心脏和大血管相关手术；严重心律失常包括频发室早、室性心动过速、快速房颤/房扑、严重心动过缓。未控制的高血压：大于 150/100mmHg）。胃溃疡（研究者判定有穿孔风险的胃溃疡）；活动性自身免疫性疾病；严重高血压；严重呼吸系统疾病（如阻塞性肺病和支气管痉挛史）等。
13. 任何一个 CHOP 中所包括的任何药物有禁忌，包括既往接受的蒽环类抗生素；糖尿病患者不能耐受本方案中泼尼松治疗者。
14. 受试者有酗酒史或药物滥用史。
15. 过敏体质、或已知对本试验（包括 CHOP 方案）中所包含的任何药物有效成分、辅料或者鼠源制品、异种蛋白过敏者。
16. 有严重精神疾病者。
17. 在试验和/或随访阶段无法依从的患者。
18. 研究者认为不适合入组者。

Exclusion criteria：

1. Other types of DLBCL: chronic inflammation related DLBCL, lymphoma like granuloma, primary mediastinal large B-cell lymphoma, ALK positive large B-cell lymphoma, primary exudative lymphoma, Burkitt lymphoma, advanced B-cell lymphoma (including advanced B-cell lymphoma, NOS and advanced B-cell lymphoma with myc and BCL2 and / or BCL6 rearrangement), B Cell lymphoma can not be classified (between DLBCL and classical Hodgkin's lymphoma), primary central nervous system (CNS) DLBCL, EBV (+ DLBCL);
2. Transformed DLBCL (such as follicular lymphoma, chronic lymphoblastic leukemia / small B-cell lymphoma) with secondary central nervous system invasion.
3. In the past 5 years, patients with skin squamous cell carcinoma, skin basal cell carcinoma, cervical carcinoma in situ and other malignant tumor history;
4. Patients who have undergone major surgery in the past 2 months (excluding diagnostic surgery);
5. Patients who have received NHL treatment: including chemotherapy, immunotherapy, radiotherapy, monoclonal antibody treatment, surgical treatment (excluding diagnostic surgery and biopsy);
6. Patients who have previously received cytotoxic drugs or mAb CD20 antibody to treat other diseases (such as rheumatoid arthritis);
7. Patients who have previously received thalidomide, lenalidomide and other drugs;
8. Patients who have used any monoclonal antibody, participated in other clinical trials and used other test related drugs in the first three months of enrollment, and who have been vaccinated (attenuated) live virus vaccine in the first one month of enrollment;
9. Patients who had used hematopoietic cytokines within 2 weeks before admission;
10. Patients suspected of active or latent tuberculosis;
11. Patients with active bacteria, virus, fungus, Mycobacterium, parasite infection or other infection (excluding fungal infection of nail bed skin) or any major systemic infection event requiring intravenous antibiotic treatment or hospitalization (excluding tumor fever) are known within 4 weeks before enrollment;
12. Patients with other serious diseases that may limit their participation in the trial, such as: uncontrolled diabetes mellitus; severe cardiac insufficiency (NYHA grade II or above); acute coronary syndrome within the past 6 months; and In June, coronary artery revascularization, such as stent implantation, coronary artery bypass grafting, and other heart and large blood vessel related operations; severe arrhythmias include frequent ventricular premature, ventricular tachycardia, rapid atrial fibrillation / atrial flutter, and severe bradycardia. Uncontrolled hypertension: more than 150 / 100mmhg). Gastric ulcer (gastric ulcer at risk of perforation determined by researchers); active autoimmune disease; severe hypertension; severe respiratory diseases (such as history of obstructive pulmonary disease and bronchospasm), etc.;
13. Patients with contraindications to any drug included in any chop, including anthracycline antibiotics previously received; diabetics who could not tolerate prednisone treatment in this protocol;
14. Subjects had a history of alcohol or drug abuse;
15. Patients who are allergic to constitution, or known to be allergic to any active ingredients, excipients or mouse derived products or heteroprotein contained in this trial (including the chop protocol);
16. Patients with serious mental illness;
17. Patients who are unable to comply during the trial and / or follow-up phase;
18. The researchers think it is not suitable for the patients in the group.

研究实施时间：

Study execute time：

从 From 2021-01-01 00:00:00至 To 2023-12-31 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2020-06-10 00:00:00 至 To 2020-12-31 00:00:00

干预措施：

Interventions：

组别：	试验组	样本量：	80
Group：	experimental group	Sample size：	80
干预措施：	来那度胺联合利妥昔单抗、长春新碱、阿霉素、环磷酰胺、泼尼松	干预措施代码：
Intervention：	R2-CHOP	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	广东	市(区县)：	广州
Country：	China	Province：	Guangdong	City：	Guangzhou
单位(医院)：	中山大学肿瘤防治中心	单位级别：	三级甲等
Institution hospital：	Cancer Prevention and Treatment Center, Sun Yat-Sen 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：	CRR	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：	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：	总生存期	指标类型：	次要指标
Outcome：	OS	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	总生存期	指标类型：	次要指标
Outcome：	PFS	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：	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：

标本中文名：	尿液	组织：
Sample Name：	Urine	Tissue：
人体标本去向	使用后销毁	说明
Fate of sample：	Destruction after use	Note：

标本中文名：	粪便	组织：
Sample Name：	feces	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	18	岁 years
最大 Max age	80	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）：

未使用

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

Not used

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：	N/A
Blinding：	N/A

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）：	原始数据不公开
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	Raw data is not made public
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：	暂未确定/Not yet
注册人： Name of Registration：	2020-06-02 14:55:47