ChiCTR-TNC-10000782 版本V1.3 版本创建时间2019/04/16 15:50:06 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：

 ChiCTR-TNC-10000782 

最近更新日期：

Date of Last Refreshed on：

 2019-04-16 15:49:07 

注册时间：

Date of Registration：

 2010-02-10 00:00:00 

注册号状态：

补注册

Registration Status：

Retrospective registration

注册题目：

吉西他滨、左旋门冬酰胺酶、异环磷酰胺、地塞米松及足叶乙甙（GLIDE）方案治疗初发III/IV期及复发难治侵袭性NK/T细胞淋巴瘤的临床试验

Public title：

Gemcitabine, L-asparaginase, Isophosphomide, Dexamethasone and Etoposide (GLIDE) In Patients with Newly Diagnosed Stage III/IV and Recurrent or Refractory Aggressive NK/T Cell Lymphoma

注册题目简写：

English Acronym：

研究课题的正式科学名称：

吉西他滨、左旋门冬酰胺酶、异环磷酰胺、地塞米松及足叶乙甙（GLIDE）方案治疗初发III/IV期及复发难治侵袭性NK/T细胞淋巴瘤的临床试验

Scientific title：

Gemcitabine, L-asparaginase, Isophosphomide, Dexamethasone and Etoposide (GLIDE) In Patients with Newly Diagnosed Stage III/IV and Recurrent or Refractory Aggressive NK/T Cell 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：

季杰 

研究负责人：

季杰 

Applicant：

Jie Ji 

Study leader：

Jie Ji 

申请注册联系人电话：

Applicant telephone：

 +86 13086660487

研究负责人电话：

Study leader's
telephone：

+86 13086660487

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：

 seasonj@gmail.com

研究负责人电子邮件：

Study leader's E-mail：

 seasonj@gmail.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：

中国成都市国学巷37号

研究负责人通讯地址：

中国成都市国学巷37号

Applicant address：

37 Guoxuexiang, Chengdu, Sichuan, China

Study leader's address：

37 Guoxuexiang, Chengdu, Sichuan, China

申请注册联系人邮政编码：

Applicant postcode：

 610041

研究负责人邮政编码：

Study leader's postcode：

 610041

申请人所在单位：

四川大学华西医院血液科

Applicant's institution：

Department of Hematology, West China Hospital, SCU

研究负责人所在单位：

四川大学华西医院血液科

Affiliation of the Leader：

Department of Hematology, West China Hospital, SCU

是否获伦理委员会批准：

否

Approved by ethic committee：

No

伦理委员会批件文号：

Approved No. of ethic committee：

伦理委员会批件附件：

Approved file of Ethical Committee：

批准本研究的伦理委员会名称：

Name of the ethic committee：

伦理委员会批准日期：

Date of approved by ethic committee：

 2013-08-26 00:00:00

伦理委员会联系人：

Contact Name of the ethic committee：

伦理委员会联系地址：

Contact Address of the ethic committee：

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：

四川大学华西医院

Primary sponsor：

West China Hospital

研究实施负责（组长）单位地址：

中国成都市国学巷37号

Primary sponsor's address：

37 Guoxuexiang, Chengdu, Sichuan, China

试验主办单位(项目批准或申办者)：

Secondary sponsor：

经费或物资来源：

自筹

Source(s) of funding：

Self funding

研究疾病：

侵袭性NK/T细胞淋巴瘤（结外鼻型NK/T细胞淋巴瘤，侵袭性NK/T细胞白血病）  

Target disease：

aggressive NK/T cell lymphoma (Extranodal NK/T cell lymphoma, nasal type; aggressive NK/T cell 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：

 探索性研究/预试验 

Study phase：

0

研究设计：

单臂 

Study design：

Single arm 

研究目的：

评价GLIDE方案治疗初治的III/IV期和复发难治的侵袭性NK/T细胞淋巴瘤的有效性和安全性  

Objectives of Study：

To evaluate the efficacy and safty of GLIDE regiment for patients with newly diagnosed stage III/IV or recurrent or refractory aggressive NK/T cell lymphoma

药物成份或治疗方案详述：

这是一项多中心II期前瞻性单臂临床试验 GLIDE化疗方案：吉西他滨800 mg/m2，第1、5天；培门冬酶 2500 u/m2第4、11天或左旋门冬酰胺酶6000 u/m2第4、6、8、10、12，异环磷酰胺1000 mg/m2 第1-3天，依托泊苷100 mg/m2 第1-3天，地塞米松20 mg 第1-4天。如果化疗第5天出现3级以上血液学毒性，第5天吉西他滨用药跳过。如果治疗过程中出现对门冬酰胺酶过敏，在随后的治疗疗程中门冬酰胺酶不再使用。粒细胞集落刺激因子从化疗第5天起至中性粒细胞恢复至2×109/L以上。化疗间隔时间为4周，在新一个周期化疗前，非血液学毒性反应需在2级以下，中心粒细胞计数需达到2×109/L以上，血小板计数需达到75×109/L以上。如果不良反应未恢复到治疗要求，则推迟1周治疗。治疗计划6疗程GLIDE化疗，每2疗程进行一次疗效评估。 疗效评估达到完全缓解（CR）或6疗程结束达到部分缓解（PR）的患者根据其移植医院安排外周血造血干细胞采集。完成总共6疗程，并愿意接受自体移植的患者于四川大学华西医院造血干细胞移植中心接受西达本胺、克拉屈滨、吉西他滨及白消安（ChiCGB）预处理方案后回输自体造血干细胞。移植后支持治疗包括输血、抗感染及集落刺激因子使用按照中心标常规案实施。 化疗期间需收集所有不良事件，移植期间收集非血液学不良事件。不良事件的名称及分级参照CTCAE 3.0 

Description for medicine or protocol of treatment in detail：

This is a multi-center phase II prospective single-arm trial. The dose and schedule of GLIDE chemotherapy was administered as following: gemcitabine 800 mg/m2, day 1,5; peg-asparaginase 2500 u/m2, day 4,11; ifosfamide 1000 mg/m2, day 1-3; etoposide 100mg/m2, day 1-3; dexamethasone 20mg day 1-4. Gemcitabine on day 5 should be skipped if any grade 3 or above hematologic toxicities developed. Peg-asparaginase should be discontinued if patients developed any asparaginase related allergic reaction. Granulocyte colony stimulating factor was started on day 5 till full recovery of absolute neutrophils count (ANC, defined as above 2×109/L). The interval between 2 cycles of chemotherapy is 4 weeks and before initiation of a new cycle of chemotherapy, severity of all non-hematologic adverse events must be less than grade 2, ANC above 2×109/L and platelets count above 80×109/L. If adverse events failed to recover, the following cycle of chemotherapy should be postponed for one week. If there was no recovery 4 weeks before the day of the scheduled following cycle, the protocol treatment was terminated. Totally, 6 cycles of GLIDE chemotherapy were planned for protocol treatment. Response of lymphoma should be evaluated every 2 cycles. Hematopoietic stem cells of patients with best response better than partial response (PR), including PR and complete response (CR) after up to 6 cycles of GLIDE, were collected. When complete response is attained, peripheral hematopoietic stem cells should be collected. Fitted patients will treated with chidamide, cladribine, gemcitabine and busulfan (ChiCGB) conditioning followed by autologous stem cell transplantation (ASCT). Patients who are unable to receive ASCT, continued with GLIDE for up to 6 cycles. Patients who are unable to attain PR after 6 cycles of GLIDE, drop off this trial. Response and Toxicity Evaluation Baseline evaluations were finished 10 days before enrollment, including history, physical examination, complete blood count, serum liver and kidney function, serum lactate dehydrogenase level, marrow smear and biopsy, enhanced computer tomography of neck, thorax, abdomen and pelvis and endoscopic investigation of gastrointestinal tract if such sites involvement were indicated. Response was regularly evaluated after every two cycles of GLIDE chemotherapy using the revised response criteria for malignant lymphoma. Therefore, in this trial, complete response (CR) was defined as the complete disappearance of all objective signs of disease, including enlarged lymph nodes or hepatomegaly and splenomegaly at the restaging. Partial response (PR) was defined as at least a 50% reduction of tumor volume without the occurrence of new lesions at the restaging. Progressive disease was defined as a greater than 25% increase in the sum of tumor lesions or the emergence of one or more new lesion(s) or clinical symptoms that indicate disease progression. No response was defined as any response that did not fall into the other defined categories. The toxicity of treatment was graded using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. 

纳入标准：

1、经病理组织学及免疫组织化学确诊的I/II期鼻型NK/T淋巴瘤患者。2、ECOG评分0-2分，无化疗禁忌症。3、预计生存期3个月以上。4、患者自愿参加并签署知情同意书。

Inclusion criteria

1. Diagnosis of aggressive NK/T cell lymphoma by histology and immunochemistry based on WHO 2008. Stage I and II lymphoma will not be permitted to enter study;
2. Eastern Cooperative Oncology Group (ECOG) status 0-2;
3. All patients have to sign an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study;
4. Estimated survival time > 3 months.

排除标准：

1、妊娠妇女或正在哺乳期妇女；2、任何无法控制的临床问题（如严重的精神、神经、心血管、呼吸、活动性感染等系统疾病）；3、已知对任何研究用药过敏的患者；

Exclusion criteria：

1. Pregnent or breast-feeding women;
2. Active systemic infection requiring treatment and patients with known diagnosis of HIV or active hepatitis B;
3. Serious medical or psychiatric illness likely to interfere with participation in this clinical study.

研究实施时间：

Study execute time：

从 From 2011-01-01 00:00:00至 To 2014-12-31 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2010-01-01 00:00:00 至 To 2012-12-31 00:00:00

干预措施：

Interventions：

组别：

治疗组

样本量：

 10

Group：

Treatment group

Sample size：

干预措施：

吉西他滨 800mg/m^2 D1,8，左旋门冬酰胺酶 6000mg/m^2 D8,10,12,14,16,18,20，异环磷酰胺1g/m^2 D1-3，地塞米松40mg D1-4,D9-12（肠道淋巴瘤第一疗程给与强的松100mg D1-5），足叶乙甙 100mg/m^2 D1-3。总疗程6-8疗程。

干预措施代码：

Intervention：

Gemcitabine 800mg/m^2 Day1, 8; L-ASP 6000mg/m^2 Day 8, 10, 12, 14, 16, 18, 20; isophosphomide 1g/m^2 Day 1-3; Dexamethasone 40mg Day 1-4, Day 9-12 (prednisone 100mg Day 1-5 for first cyle of gastrointestianl lymphoma); etopside 100mg//m^2 Day 1-3. 6 to 8 cycles in total

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 四川 

市(区县)：

  

Country：

China

Province：

Sichuan

City：

单位(医院)：

 四川大学华西医院 

单位级别：

 三级甲等 

Institution
hospital：

West China Hospital, SCU

Level of the institution：

Tertiary A hospital

测量指标：

Outcomes：

指标中文名：

2年无病生存率

指标类型：

主要指标

Outcome：

2-years disease free survival

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

完全缓解率

指标类型：

次要指标

Outcome：

complete response rate

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

有效率

指标类型：

次要指标

Outcome：

overall response rate

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

2年总生存率

指标类型：

次要指标

Outcome：

2-year overall survival

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

III、IV级不良反应

指标类型：

次要指标

Outcome：

grade III and IV adverse event

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：

征募研究对象情况：

Recruiting status：

结束

/Completed

年龄范围：

Participant age：
最小 Min age 15 岁 years
最大 Max age 65 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）：

NA

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

NA

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）：

Not stated

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

Not stated

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：

Department of Hematology, West China Hospital, SCU

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

Department of Hematology, West China Hospital, SCU

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：

  2015-06-05 21:00:26