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A Phase I Clinical Trial of BAT4306F (for injection) on Safety, Tolerability and Pharmacokinetics for Patients with CD20-positive, B-cell non-Hodgkin's lymphoma
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注册号:

Registration number:

ChiCTR1800018900 

最近更新日期:

Date of Last Refreshed on:

2018-10-16 

注册时间:

Date of Registration:

2018-10-16 

注册号状态:

预注册  

Registration Status:

Prospective registration  

注册题目:

一项评价BAT4306F注射液在复发/难治CD20阳性B细胞性非霍奇金淋巴瘤患者中的安全性、耐受性和药代动力学的I期临床研究 

Public title:

A Phase I Clinical Trial of BAT4306F (for injection) on Safety, Tolerability and Pharmacokinetics for Patients with CD20-positive, B-cell non-Hodgkin's lymphoma 

注册题目简写:

 

English Acronym:

 

研究课题的正式科学名称:

一项评价BAT4306F注射液在复发/难治CD20阳性B细胞性非霍奇金淋巴瘤患者中的安全性、耐受性和药代动力学的I期临床研究 

Scientific title:

A Phase I Clinical Trial of BAT4306F (for injection) on Safety, Tolerability and Pharmacokinetics for Patients with CD20-positive, B-cell non-Hodgkin's 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:

郑惠芬 

研究负责人:

朱军 

Applicant:

Zheng Huifen 

Study leader:

Zhu Jun 

申请注册联系人电话:

Applicant telephone:

+86 18620667595 

研究负责人电话:

Study leader's telephone:

+86 13910333346 

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:

hfzheng@bio-thera.com 

研究负责人电子邮件:

Study leader's E-mail:

zhujun@csco.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:

广州市天河区天河北路908号高科大厦B栋608室 

研究负责人通讯地址:

北京市海淀区阜成路52号 

Applicant address:

Room 608, Tower B, Hi-Tech Building, 908 Tian-He Road North, Tian-He District, Guangzhou, Guangdong, China. 

Study leader's address:

52 Fucheng Road, Haidian District, Beijing, 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:

百奥泰生物科技(广州)有限公司 

Applicant's institution:

Bio-thera Solutions,Ltd. 

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:

2018YW34 

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:

北京肿瘤医院医学伦理委员会 

Name of the ethic committee:

The Medical Ethics Committee Of Beijing Cancer Hospital  

伦理委员会批准日期:

Date of approved by ethic committee:

2018-07-06 

伦理委员会联系人:

黄珺 

Contact Name of the ethic committee:

Huang Jun 

伦理委员会联系地址:

北京市海淀区阜成路52号 

Contact Address of the ethic committee:

52 Fucheng Road, Haidian District, Beijing, China 

伦理委员会联系人电话:

Contact phone of the ethic committee:

+86 10-88196391 

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:

北京肿瘤医院 

Primary sponsor:

Beijing Cancer Hospital 

研究实施负责(组长)单位地址:

北京市海淀区阜成路52号 

Primary sponsor's address:

52 Fucheng Road, Haidian District, Beijing, 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):

百奥泰生物科技(广州)有限公司

具体地址:

中国广东省广州市黄埔区科学城开源大道11号科技企业加速器A6栋5楼

Institution
hospital:

Bio-thera Solutions,Ltd.

Address:

Floor 5, Building A6, Science Enterprise Accelerator, 11 Kaiyuan Avenue, Science City, Huangpu District, Guangzhou, Guangdong, China

经费或物资来源:

自筹 

Source(s) of funding:

Self-raised funds 

研究疾病:

复发/难治CD20阳性B细胞性非霍奇金淋巴瘤 

Target disease:

Relapse/Refractory CD20+ B Cell Non-hodgkin's Lymphoma 

研究疾病代码:

 

Target disease code:

 

研究类型:

治疗研究 

Study type:

Treatment study 

研究所处阶段:

I期临床试验 

Study phase:

研究目的:

1)评价BAT4306F注射液剂量递增在CD20阳性B细胞淋巴瘤患者中的安全性、耐受性,以确定最大耐受剂量(MTD)、剂量限制性毒性(DLT)和推荐II期临床研究的使用剂量(RP2D); 2)研究BAT4306F注射液的药代动力学特征; 3)1)研究BAT4306F注射液的免疫原性; 4)2)研究BAT4306F的药效学特征;采用Lugano标准(2014年)、2008?IWCLL疗效评价标准、2014 IWWM-7疗效评价标准,在第7周、第13周、第19周进行相关疾病的疗效评价,评价指标为ORR(包括CR,PR,SD和PD,ORR为出现CR和PR的患者比例)。 To evaluate the efficacy profile of BAT4306F (for injection)。 

Objectives of Study:

1. The primary objective of the study is to evaluate the safety and tolerability of BAT4306F in patients with CD20-positive B-cell lymphoma, when the injection dosage escalates, to ultimately determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and recommended dosage for phase II clinical studies ( RP2D); 2. To evaluate the pharmacokinetics (PK) of BAT4306F(for injection); 3. To evaluate the immunogenicity profile of BAT4306F(for injection); 4. To evaluate the efficacy profile of BAT4306F (for injection);Using the Lugano criteria (2014), the 2008 IWCLL efficacy evaluation criteria, and the 2014 IWWM-7 efficacy evaluation criteria were used to evaluate the efficacy of related diseases at week 7, week 13, and week 19. The index of evaluation was ORR (including CR, PR, SD and PD, ORR is the proportion of patients with CR and PR). 

药物成份或治疗方案详述:

 

Description for medicine or protocol of treatment in detail:

 

研究设计:

不同剂量对照 

Study design:

Dose comparison 

纳入标准:

1)同意参加试验,并书面签署知情同意书; 2)年龄18-75周岁,性别不限; 3)病理组织学已证明CD20阳性,既往至少接受1个疗程的标准抗肿瘤方案治疗的复发/难治/进展的非霍奇金淋巴瘤患者; 4)具有至少一个可测量的病灶:CLL患者单克隆B细胞≥5╳109/L。WM患者IgM大于2倍正常值上限。CLL和WM以外的患者,淋巴结病灶任一长径≥1.5cm或结外病灶任一长径>1cm; 5)如果以往放、化疗引起毒副反应,则需要恢复至≤1级或转归至基线值或被判定不可逆(脱发和≤2级神经毒性除外); 6)患者ECOG 评分为0-2分; 7)预期生存期至少为6个月; 8)受试者必须具有有适当的器官功能,入组前符合下列所有实验室检查结果: 骨髓储备基本正常:中性粒细胞(ANC)≥1.0×109/L,血红蛋白(HB)≥70 g/L,血小板(PLT)≥50×109/L。(骨髓侵犯、B-NHL相关自身免疫性血细胞减少的除外,骨髓侵犯根据骨髓活检、骨髓涂片、以及骨髓流式细胞学结果判断。) 肝功能基本正常:ALT≤2.5×ULN,AST≤2.5×ULN,TBIL≤1.5×ULN(肝脏侵犯的除外。有B-NHL相关自身免疫性溶血性贫血的患者,TBIL不受此限); 肾功能基本正常:肌酐≤1.5×ULN,或肌酐清除率≥ 60mL/min; 凝血常规基本正常:INR≤1.5×ULN,APTT不超过正常对照10秒; 9)育龄女性受试者的血清妊娠试验呈阴性; 10)患者若为男性,必须为经手术节育的男性,或在研究期间及研究药物停用后12个月内采用某种高效的避孕方法。若为女性,则必须经节育手术、或处于绝经期或在研究期间以及研究药物停用后12个月内采取某种高效的避孕措施,并且在研究期间以及研究药物停用后12个月内避免哺乳。 

Inclusion criteria

To be eligible for study entry subjects must satisfy all of the following criteria: 1. Must be willing to provide written consent 2. Male or female, 18 years old or older 3. Histopathology test confirmed CD20-positive patients with relapsed/refractory/progressive non-Hodgkin's lymphoma, who have been treated with at least one course of standard anti-tumor regimen; 4. Has at least one measurable lesion: CLL patient monoclonal B cells≥5x 10^9/L. IgM in WM patients is greater than 2 times of the upper limit of normal. In patients other than CLL and WM, any diameter of the lymph node lesion ≥1.5cm or any extranodal lesion >1cm; 5. If the previous radiotherapy and chemotherapy cause toxic side effects, it needs to be restored to at least level 1 or returned to the baseline value or to be judged as irreversible (except for neurotoxicity related to grade 2 alopecia or platinum-containing treatment); 6. The patient's ECOG score was 0-2 points; 7. Expected survival is at least 6 months; 8. Subjects must have appropriate organ function and meet all of the following laboratory findings prior to enrollment: 1) The bone marrow reserve was basically normal: neutrophils (ANC) ≥ 1.0 × 10^9/L, hemoglobin (HB) ≥ 70 g/L, platelets (PLT) ≥ 50×10^9/L (Except for bone marrow invasion, B-NHL-related autoimmune cytopenia. bone marrow invasion will be judged by bone marrow biopsy, bone marrow smear, and bone marrow flow cytology results.) 2) Liver function is basically normal: ALT ≤ 2.5×ULN, AST ≤ 2.5×ULN, TBIL ≤ 1.5×ULN (except for liver invasion. Patients with B-NHL-related autoimmune hemolytic anemia, TBIL is not subject to this limit); 3) Renal function is basically normal: creatinine ≤ 1.5×ULN, or creatinine clearance ≥ 60mL/min; 4) The conventional coagulation examinations is basically normal: INR ≤ 1.5×ULN, APTT does not exceed the normal reference for 10 seconds; 9. Fertile female must be tested negative for serum pregnancy test; 10. If the patient is a male, it must be a male who has undergone surgical birth control, or use of an effective contraceptive method during the study period and within 12 months after the study drug is discontinued. In the case of female, an effective contraceptive procedure must be taken or during menopause or use of an effective contraceptive method during the study period and within 12 months of the study drug discontinuation, and avoid breastfeeding during the study period and within 12 months of the study drug discontinuation. 

排除标准:

如果患者符合以下条件的任何一条,则不能进入本研究: 1)首次给药前3个月内使用过任何研究用单克隆抗体治疗; 2)既往使用过任何抗癌疫苗,或研究给药前3个月内使用过HPV疫苗; 3)首次给药前3个月内使用过抗CD20单抗治疗的; 4)首次给药前3个月内使用过放射免疫疗法; 5)首次给药前2周内接受过输血、促红细胞生成素、粒细胞集落刺激因子或粒细胞-巨噬细胞集落刺激因子的治疗; 6)首次给药前3个月进行过造血干细胞移植或计划在3个月内进行造血干细胞移植的; 7)对人源化或鼠源化单克隆抗体有严重过敏反应的病史。已知对鼠源类产品存在高反应性或过敏; 8)中枢神经系统侵犯或颅脑神经病变的证据或病史; 9)并发有其他恶性肿瘤者(已经治愈的原位宫颈癌,皮肤癌,获得完全缓解>5年的乳腺癌、黑色素瘤除外); 10)其他严重的、无法控制的伴随疾病,包括但不限于:活动性感染、不能控制的糖尿病、不能控制的高血压病等; 11)首次给药前4周内或预计研究期间进行重大手术,或手术伤口未愈合者; 12)患有类风湿关节炎患者,肉芽肿血管炎或显微镜下多血管炎的患者,有中毒性表皮坏死松解症或Stevens-Johnson综合症的患者; 13)有慢性特发性肠道疾病,包括克罗恩病(Crohn’s disease)和溃疡性结肠炎(Ulcerative Colitis)等病史,肠梗阻患者;慢性腹泻患者; 14)可能会导致以下结果的其它既往史、急性或慢性疾病、精神疾病或实验室检测值异常:增加研究参与或研究药物给药的相关风险,或干扰研究结果的解读等; 15)怀孕或哺乳期女性; 16)首次给药前4周内在另一项临床研究中接受过治疗; 17)首次给药前4周内接收高剂量皮质类固醇治疗(氢化泼尼松大于20mg天或相当剂量的其他药物,持续2周及以上)的患者; 18)病毒学检查:HBsAg阳性;HBcAb阳性且 HBV-DNA检测≥检测上限;HCV抗体阳性且HCV-RNA≥检测正常值上限;HIV抗体阳性;梅毒感染阳性。 19)研究者认为不适合入组的患者。 

Exclusion criteria:

Subjects will be excluded from the study if one or more of the following criteria are applicable: 1. Treatment with any monoclonal antibody within 3 months prior to the first dose; 2. Have used any anti-cancer vaccine in the past, or have used the HPV vaccine within 3 months prior to the study; 3. Used anti-CD20 mAb within 3 months prior to the first dose; 4. Radioimmunotherapy was used within 3 months prior to the first dose; 5. Treatment of transfusion, erythropoietin, granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor within 2 weeks prior to the first dose; 6. Hematopoietic stem cell transplantation was performed 3 months before the first administration or hematopoietic stem cell transplantation was planned in 3 months; 7. A history of severe allergic reactions to humanized or murine monoclonal antibodies. (or is high reactivity / allergy to murine-derived products); 8. Evidence or medical history of central nervous system invasion or cranial neuropathy; 9. Concurrent with other malignant tumors (except for in situ cervical cancer, skin cancer, complete remission > 5 years of breast cancer and melanoma); 10. Other serious, uncontrollable concomitant diseases, including but not limited to: active infections, uncontrolled diabetes, uncontrollable hypertension, etc.; 11. Major surgery performed within 4 weeks prior to the first dose or during the expected study period, or if the surgical wound is not healed; 12. Patients with rheumatoid arthritis, granulomatous vasculitis, microscopic polyangiitis, toxic epidermal necrolysis or Stevens-Johnson syndrome; 13. Patients with chronic idiopathic bowel disease (including history of Crohns disease and Ulcerative Colitis), with intestinal obstruction or with chronic diarrhea; 14. Other past history, acute or chronic disease, mental illness, or laboratory test abnormalities that may result in increased risk of involvement in study or study drug administration, or interference in interpretation of research findings; 15. Pregnant or lactating women; 16. Received treatment in another clinical study within 4 weeks prior to the first dose; 17. Patients receiving high-dose corticosteroids (prednisolone greater than 10 mg/day or equivalent dosage of other drugs for 2 weeks or more) within 4 weeks prior to the first dose; 18. Virological examination: HBsAg positive; HBcAb positive and HBV-DNA detection ≥ detection upper limit; HCV antibody positive; HIV antibody positive; syphilis infection positive. 19. Subject is considered by the investigator, for any reason, to be an unsuitable candidate for the study. 

研究实施时间:

Study execute time:

From2018-03-06To  

干预措施:

Interventions:

组别:

500mg

样本量:

6

Group:

500mg

Sample size:

干预措施:

BAT4306F注射液:100mg/4mL,静脉滴注。

干预措施代码:

Intervention:

BAT4306F Injection: 100mg/4ml, BAT4306F 100mg/4mL, IV

Intervention code:

组别:

1000mg

样本量:

6

Group:

1000mg

Sample size:

干预措施:

BAT4306F注射液:100mg/4mL,静脉滴注。

干预措施代码:

Intervention:

BAT4306F Injection 100mg/4ml, BAT4306F 100mg/4mL, IV

Intervention code:

组别:

1500mg

样本量:

6

Group:

1500mg

Sample size:

干预措施:

BAT4306F注射液:100mg/4mL,静脉滴注。

干预措施代码:

Intervention:

BAT4306F Injection 100mg/4ml, BAT4306F 100mg/4mL, IV

Intervention code:

组别:

1500mg

样本量:

6

Group:

1500mg

Sample size:

干预措施:

BAT4306F注射液:100mg/4mL,静脉滴注。

干预措施代码:

Intervention:

BAT4306F Injection 100mg/4ml, BAT4306F 100mg/4mL, IV

Intervention code:

研究实施地点:

Countries of recruitment and research settings:

国家:

中国 

省(直辖市):

北京 

市(区县):

北京 

Country:

China 

Province:

Beijing 

City:

Beijing 

单位(医院):

北京肿瘤医院 

单位级别:

三甲医院 

Institution
hospital:

Beijing Cancer Hospital  

Level of the institution:

Tertiary A Hospital 

国家:

中国 

省(直辖市):

天津 

市(区县):

天津 

Country:

China 

Province:

Tianjin 

City:

Tianjin 

单位(医院):

中国医学科学院血液病医院 

单位级别:

三甲医院 

Institution
hospital:

Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College  

Level of the institution:

Tertiary A Hospital 

测量指标:

Outcomes:

指标中文名:

最大耐受剂量

指标类型:

主要指标 

Outcome:

MTD

Type:

Primary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

剂量限制性毒性

指标类型:

主要指标 

Outcome:

DLT

Type:

Primary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

药代动力学

指标类型:

主要指标 

Outcome:

PK

Type:

Primary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

免疫原性

指标类型:

次要指标 

Outcome:

ADA

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

药效学特征

指标类型:

次要指标 

Outcome:

PD

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

ORR

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:

采集人体标本:

Collecting sample(s)
from participants:

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 years
最大 Max age 75 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):

无随机

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

NA

盲法:

N/A

Blinding:

N/A

原始数据公开时间:

The time of sharing IPD:

Within six months after the trial complete

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):

CSR 2020年12月

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

CSR 2012-12

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:

电子采集和管理系统

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

Electronic Data Capture, EDC

数据管理委员会:

Data Managemen Committee:

暂未确定/Not yet

注册人:

Name of Registration:

 2018-10-16
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