ChiCTR2200058738 版本V1.0 版本创建时间2022/04/16 10:14:08 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：

 ChiCTR2200058738 

最近更新日期：

Date of Last Refreshed on：

 2022-04-16 10:14:02 

注册时间：

Date of Registration：

 2022-04-16 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

请结合研究计划书进一步完善测量指标的填写 CAR-T治疗多发性骨髓瘤患者的单臂、非盲的安全性及有效性 临床研究

Public title：

A single-arm, unblinded safety and efficacy of CAR-T therapy in patients with multiple myeloma clinical research

注册题目简写：

English Acronym：

研究课题的正式科学名称：

CAR-T治疗多发性骨髓瘤患者的单臂、非盲的安全性及有效性 临床研究

Scientific title：

A single-arm, unblinded safety and efficacy of CAR-T therapy in patients with multiple myeloma clinical research

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：

黎国伟 

研究负责人：

黎国伟 

Applicant：

Guowei Li 

Study leader：

Guowei Li 

申请注册联系人电话：

Applicant telephone：

 0752－2288958

研究负责人电话：

Study leader's
telephone：

0752－2288958

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：

 hzligw@163.com

研究负责人电子邮件：

Study leader's E-mail：

 hzligw@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：

广东省惠州市鹅岭北路41号

研究负责人通讯地址：

广东省惠州市鹅岭北路41号

Applicant address：

No. 41,Er Ling Bei Road,Huizhou,Guangdong

Study leader's address：

No. 41,Er Ling Bei Road,Huizhou,Guangdong

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：

惠州市中心人民医院

Applicant's institution：

Huizhou Municipal Central Hospital

研究负责人所在单位：

Affiliation of the Leader：

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：

 kyll2021209

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：

惠州市中心人民医院临床科研伦理委员会

Name of the ethic committee：

Medical Ethics Committee of Huizhou Municipal Central Hospital

伦理委员会批准日期：

Date of approved by ethic committee：

 2021-09-06 00:00:00

伦理委员会联系人：

袁霞

Contact Name of the ethic committee：

Yuan Xia

伦理委员会联系地址：

广东省惠州市鹅岭北路41号

Contact Address of the ethic committee：

No. 41,Er Ling Bei Road,Huizhou,Guangdong

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：

惠州市中心人民医院

Primary sponsor：

Huizhou Municipal Central Hospital

研究实施负责（组长）单位地址：

广东省惠州市鹅岭北路41号

Primary sponsor's address：

No. 41,Er Ling Bei Road,Huizhou,Guangdong

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)：

Country：

China

Province：

Guangdong

City：

单位(医院)：

惠州市中心人民医院

具体地址：

广东省惠州市鹅岭北路41号

Institution
hospital：

Huizhou Municipal Central Hospital

Address：

No. 41,Er Ling Bei Road,Huizhou,Guangdong

经费或物资来源：

广州百暨基因科技有限公司

Source(s) of funding：

Guangzhou Bio-gene Technology Co., Ltd

研究疾病：

多发性骨髓瘤  

Target disease：

multiple myeloma

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BCMA CAR-T单剂量输注在多发性骨髓瘤患者中的安全性及有效性  

Objectives of Study：

To evaluate the safety and efficacy of BCMA CAR-T single-dose infusion in patients with multiple myeloma

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）年龄≥5岁的中国受试者；
2）根据IMWG诊断标准，诊断为多发性骨髓瘤的患者。
3）根据以下任一标准确定筛选时存在可测量病灶：血清单克隆副蛋白（M-蛋白）水平≥1.0 g/dL 或尿M蛋白水平≥200 mg/24小时；或血清或尿液中无可测量病灶的轻链型多发性骨髓瘤：血清免疫球蛋白游离轻链≥10 mg/dL且血清免疫球蛋白κ/γ游离轻链比异常。研究的特定定义：仅有FLC可测量的多发性骨髓瘤，血清或尿M蛋白水平均未达到可测量标准
4）ECOG体能状态等级≤ 2（见附录2）。
5）筛选期临床实验室数值符合以下标准：血红蛋白≥8.0 g/dL（实验室检查前7天内没有输注过红细胞[RBC]；允许使用重组人红细胞生成素，对于在筛选时符合入选标准的受试者，允许在筛选时首次血液学检查后进行红细胞输注，以维持血红蛋白水平≥8.0 g/dL）；血小板≥75×109/L（实验室检查前7天内必须未接受过输血支持）；淋巴细胞计数：≥0.3×109/L；中性粒细胞绝对计数（ANC）≥1.0×109/L（允许使用过生长因子支持，但在实验室检查前7天内必须未接受过支持治疗）；血清ALT/AST≤3.0×正常上限（ULN）；肌酐清除率≥50 mL/min，血肌酐≤2.5 mg/dL，根据肾脏疾病膳食改良公式计算或24小时尿液采集结果；总胆红素≤2.0×ULN；先天性胆红素血症受试者除外，例如Gilbert综合征（在这种情况下，要求直接胆红素≤1.5×ULN）；校正血清钙≤12.5 mg/dL（≤3.1 mmol/L）或游离离子钙≤6.5 mg/dL（≤1.6 mmol/L）；心脏射血分数≥45%，超声心动图检查确认未见心包积液，未见有临床意义的心电图发现；不存在有临床意义的胸腔积液；在室内时基线血氧饱和度>92%。
6）有生育能力的女性在筛选时和首次接受环磷酰胺和氟达拉滨治疗前的高敏感性血清妊娠试验（β人绒毛膜促性腺激素[β-hCG]）必须为阴性。
7）有生育能力的女性必须遵守下列要求：受试者必须同意采用一种高效的避孕方法，并同意在从签署知情同意书（ICF）至接受本品输注后至少100天内持续使用一种高效的避孕方法。
8）可建立采集所需的静脉通路，无白细胞采集禁忌症。
9）受试者必须签署ICF，表明其理解本研究的目的和程序并且愿意参加研究。须在开始任何一项研究相关但不属于受试者疾病标准治疗的检查或程序前获得知情同意。
10）愿意并能够遵循本方案规定的禁忌和限制事项。

Inclusion criteria

1) Chinese subjects aged ≥5 years;
2) Patients diagnosed with multiple myeloma according to IMWG diagnostic criteria.
3) The presence of measurable lesions during screening was determined according to any of the following criteria: serum m-protein level ≥1.0 g/dL or urinary M-protein level ≥200 mg/24 hours; Light chain multiple myeloma with no measurable lesions in serum or urine: ≥10 mg/dL free light chain immunoglobulin and abnormal free light chain immunoglobulin κ/γ ratio. Study specific definition: In multiple myeloma, where only FLC was measurable, serum or urinary M protein levels did not meet measurable criteria
4) ECOG physical fitness level ≤ 2 (see Appendix 2).
5) The clinical laboratory values during the screening period met the following criteria: hemoglobin ≥8.0 g/dL (no red blood cell infusion [RBC] within 7 days prior to laboratory examination; Recombinant human erythropoietin is permitted, and for subjects who meet the inclusion criteria at screening, red blood cell infusion is permitted after the first hematologic examination at screening to maintain hemoglobin levels ≥8.0 g/dL); Platelet ≥75×109/L (must not have received transfusion support within 7 days prior to laboratory examination); Lymphocyte count: ≥0.3×109/L; Neutrophil absolute count (ANC) ≥1.0×109/L (growth factor support is allowed, but must not have been supported within 7 days prior to laboratory examination); Serum ALT/AST≤3.0× normal upper limit (ULN); Creatinine clearance rate ≥50 mL/min, serum creatinine ≤2.5 mg/dL, calculated according to modified dietary formula for kidney disease or 24 hours urine collection results; Total bilirubin ≤2.0×ULN; Subjects with congenital bilirubinemia, such as Gilbert syndrome, in which direct bilirubin ≤1.5×ULN is required, are excluded; Adjusted serum calcium ≤12.5 mg/dL (≤3.1 mmol/L) or free calcium ≤6.5 mg/dL (≤1.6 mmol/L); Cardiac ejection fraction ≥45%, echocardiography examination confirmed no pericardial effusion, no clinically significant ecg findings; There was no clinically significant pleural effusion; Baseline oxygen saturation >92% indoors.
6) Fertile women must be negative for a highly sensitive serum pregnancy test (β human chorionic gonadotropin [β -HCG]) at screening time and before initial treatment with cyclophosphamide and fludarabine.
7) Fertile women must comply with the following requirements: Subjects must agree to use a highly effective contraceptive method and agree to continue using a highly effective contraceptive method for at least 100 days from signing the informed consent (ICF) to receiving the infusion.
8) The venous access required for collection can be established, without contraindications for white blood cell collection.
9) Subjects must sign an ICF indicating that they understand the purpose and procedures of the study and are willing to participate in the study. Informed consent must be obtained before initiating any study related tests or procedures that are not part of the standard treatment of the subject's disease.
10) Willing and able to follow the taboos and restrictions stipulated in the program.

排除标准：

1）曾经接受过靶向任何靶点的CAR-T治疗。
2）曾经接受过任何一种靶向BCMA的治疗。
3）被诊断为或治疗过除多发性骨髓瘤之外的其他侵袭性恶性肿瘤，但以下情况除外：接受过根治性治疗的恶性肿瘤，且在入组前≥3年内无已知活动性疾病；或经充分治疗的非黑色素瘤皮肤癌，现无疾病证据。
4）既往接受过如下抗肿瘤治疗（在单采成分血前）：在14天内或至少5个半衰期内（以更短时间为准）接受过靶向疗法、表观遗传治疗或试验性药物治疗，或使用过侵入性的试验性医疗器械。在21天内使用单克隆抗体治疗多发性骨髓瘤。在14天内接受细胞毒性治疗。在14天内接受蛋白酶体抑制剂治疗。在7天内接受免疫调节剂治疗。在14天内接受放疗。但如果射野覆盖≤5％的骨髓储备，则无论放疗结束日期是哪天，受试者都有资格参加研究。
5）除了脱发或周围神经病变外，既往抗肿瘤治疗的毒性必须好转至基线水平或≤1级
6）出现下列心脏疾病：纽约心脏协会（NYHA）III期或IV期充血性心脏衰竭 ；入组前≤6个月发作过心肌梗死或接受过冠状动脉旁路搭桥（CABG）；有临床意义的室性心律失常，或不明原因晕厥病史，非血管迷走神经性或不是由于脱水所致；严重非缺血性心肌病病史；经超声心动图或多门电路探测（MUGA）扫描评估（在单采成分血前≤8周内进行），心脏功能受损（LVEF＜45％）
7）在单采成分血前2周内接受过剂量大于5 mg/天泼尼松（或等效剂量的其他皮质类固醇）的全身性皮质类固醇治疗
8）已知活动性中枢神经系统（CNS）受累或表现出多发性骨髓瘤脑膜受累的临床体征
9）筛选时患有浆细胞白血病（按照标准分类，浆细胞＞2.0×109/L）、华氏巨球蛋白血症、POEMS综合征（多发性神经病变、脏器肿大、内分泌病变、单克隆蛋白病和皮肤改变）或原发性AL淀粉样变性。
10）人类免疫缺陷病毒（HIV）血清反应阳性。
11）在单采成分血前4周内接种过减毒活疫苗。
12）活动性乙型或丙型肝炎病毒感染者。
13）严重的基础病症，例如：有证据证明存在严重的活动性病毒、细菌感染或未控制的全身性真菌感染；活动性自身免疫性疾病或3年内的自身免疫性疾病史；有明显临床证据表明痴呆或精神状态改变。
14）不利于受试者在研究中心接受或耐受计划治疗、理解知情同意书的任何问题，或者任何研究者认为参加研究不符合受试者最佳利益（例如损害健康）的状况，或者任何可能会阻止、限制或混淆研究方案规定评估的状况。
15）参加本研究期间或接受研究治疗后100天内怀孕、哺乳或计划怀孕的女性受试者。
16）参加本研究期间或接受研究治疗后100天内有生育计划的男性受试者。

Exclusion criteria：

1) Previous CAR-T therapy targeting any target.
2) Have received any treatment targeting BCMA.
3) Have been diagnosed with or treated for invasive malignancies other than multiple myeloma, except for those who have received radical therapy and have no known active disease for ≥3 years prior to enrollment; Or adequately treated non-melanoma skin cancer with no evidence of disease.
Prior antitumor therapy (prior to monopheresis) : targeted therapy, epigenetic therapy, or experimental drug therapy, or use of an invasive experimental medical device, within 14 days or for at least 5 half-lives, whichever is less. Multiple myeloma was treated with monoclonal antibodies within 21 days. Cytotoxicity therapy was performed within 14 days. They were treated with a proteasome inhibitor within 14 days. Immunomodulators were administered within 7 days. Radiation was given within 14 days. But if the radiation field covered no more than 5% of bone marrow reserve, subjects were eligible for the study regardless of the end date of radiation therapy.
5) With the exception of alopecia or peripheral neuropathy, toxicity from previous antitumor therapy must improve to baseline or ≤ grade 1
6) Present with the following heart conditions: NYHA Stage III or IV congestive heart failure; Had myocardial infarction or received coronary artery bypass graft (CABG) ≤6 months before enrollment; A history of clinically significant ventricular arrhythmias, or unexplained syncope, non-vasovagal or not due to dehydration; A history of severe non-ischemic cardiomyopathy; Assessment of impaired cardiac function by echocardiography or multiplex circuit detection (MUGA) scan (≤8 weeks before monotherapy) (LVEF < 45%)
7) Received systemic corticosteroid therapy at a dose greater than 5 mg/ day of prednisone (or an equivalent dose of another corticosteroid) within 2 weeks prior to monotherapy
8) Active central nervous system (CNS) involvement is known or shows clinical signs of meningeal involvement in multiple myeloma
9) Had plasma cell leukemia (plasma cell > 2.0×109/L according to the standard classification), Fahrenheit macroglobulinemia, POEMS syndrome (polyneuropathy, organ enlargement, endocrine lesions, monoclonal proteinopathy, and skin changes) or primary AL amyloidosis at screening.
10) Human immunodeficiency virus (HIV) seropositivity.
11) Received live attenuated vaccine within 4 weeks prior to monopectic blood collection.
12) Infected with active hepatitis B or C virus.
13) Serious underlying medical conditions, such as evidence of severe active viral or bacterial infection or uncontrolled systemic fungal infection; Active autoimmune disease or a history of autoimmune disease within 3 years; There is clear clinical evidence of dementia or altered mental state.
14) Any issues that are not conducive to the subject's acceptance or tolerance of planned treatment at the study center, understanding of informed consent, or any condition that the investigator considers is not in the subject's best interest (e.g. harmful to health) to participate in the study, or any condition that may prevent, limit, or confuse the evaluation prescribed in the study protocol.
15) Female subjects who are pregnant, breast-feeding, or planning to become pregnant during the study period or within 100 days after the study treatment.
16) Male subjects who planned to have children during the study period or within 100 days of study treatment.

研究实施时间：

Study execute time：

从 From 2021-09-30 00:00:00至 To 2025-09-30 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2022-05-30 00:00:00 至 To 2025-05-30 00:00:00

干预措施：

Interventions：

组别：

治疗组

样本量：

 10

Group：

Treatment

Sample size：

干预措施：

输注 CAR T细胞

干预措施代码：

Intervention：

Inject CAR T cells

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)：

  

Country：

China

Province：

Guangdong

City：

单位(医院)：

 惠州市中心人民医院 

单位级别：

 三甲 

Institution
hospital：

Huizhou Municipal Central Hospital

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

客观缓解率

指标类型：

主要指标

Outcome：

overall response rate

Type：

Primary 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 5 岁 years
最大 Max age 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）：

本研究为单臂试验，无随机方法。

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

There is no random methods for single-arm study.

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）：

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：

数据管理员将在EDC系统建立eCRF

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

The data administrator will set up the eCRF on the EDC system

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2022-04-16 10:14:02