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：	ChiCTR2500108722
最近更新日期： Date of Last Refreshed on：	2025-09-04 08:40:25
注册时间： Date of Registration：	2025-09-04 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	靶向B7-H3的通用型CAR-T细胞治疗复发/难治性骨与软组织肉瘤的临床研究
Public title：	A clinical study of universal CAR-T cells targeting B7-H3 for the treatment of relapsed/refractory bone and soft tissue sarcomas
注册题目简写：
English Acronym：
研究课题的正式科学名称：	靶向B7-H3的通用型CAR-T细胞治疗复发/难治性骨与软组织肉瘤的临床研究
Scientific title：	A clinical study of universal CAR-T cells targeting B7-H3 for the treatment of relapsed/refractory bone and soft tissue sarcomas
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：	张晓帅	研究负责人：	肖建如
Applicant：	Xiaoshuai Zhang	Study leader：	Jianru Xiao
申请注册联系人电话： Applicant telephone：	+86 185 0179 5376	研究负责人电话： Study leader's telephone：	+86 137 0178 5283
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：	xiaoshuaizhang@alumni.sjtu.edu.cn	研究负责人电子邮件： Study leader's E-mail：	jianruxiao83@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：	上海市黄浦区凤阳路415号	研究负责人通讯地址：	上海市黄浦区凤阳路415号
Applicant address：	415 Fengyang Road, Shanghai 200003, P.R.China	Study leader's address：	415 Fengyang Road, Shanghai 200003, P.R.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：	上海长征医院
Applicant's institution：	Shanghai Changzheng Hospital
研究负责人所在单位：	上海长征医院
Affiliation of the Leader：	Shanghai Changzheng Hospital

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：	2025SL047	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：	上海长征医院医学伦理委员会
Name of the ethic committee：	Medical Ethics Committee, Shanghai Changzheng Hospital
伦理委员会批准日期： Date of approved by ethic committee：	2025-04-14 00:00:00
伦理委员会联系人：	孙吕平
Contact Name of the ethic committee：	Lvping Sun
伦理委员会联系地址：	上海市黄浦区凤阳路415号
Contact Address of the ethic committee：	415 Fengyang Road, Shanghai 200003, P.R.China
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 21 8188 5046	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：

上海长征医院

Primary sponsor：

Shanghai Changzheng Hospital

研究实施负责（组长）单位地址：

上海市黄浦区凤阳路415号

Primary sponsor's address：

415 Fengyang Road, Shanghai 200003, P.R.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)：	上海	市(区县)：
Country：	China	Province：	Shanghai	City：
单位(医院)：	上海长征医院	具体地址：	上海市黄浦区凤阳路415号
Institution hospital：	Shanghai Changzheng Hospital	Address：	415 Fengyang Road, Shanghai 200003, P.R.China

经费或物资来源：

自筹

Source(s) of funding：

self-financing

研究疾病：

骨与软组织肉瘤

Target disease：

Bone and soft tissue sarcomas

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：

治疗新技术临床试验

Study phase：

New Treatment Measure Clinical Study

研究设计：

单臂

Study design：

Single arm

研究目的：

一、主要研究目的评估Anti-B7-H3-UCAR-T治疗复发/难治性骨与软组织肉瘤的临床安全性和耐受性。二、次要研究目的 1、初步评价Anti-B7-H3-UCAR-T治疗复发/难治性骨与软组织肉瘤的临床有效性。 2、初步评价Anti-B7-H3-UCAR-T治疗复发/难治性骨与软组织肉瘤受试者的药代动力学特征。 3、初步评价Anti-B7-H3-UCAR-T治疗复发/难治性骨与软组织肉瘤受试者的药效动力学特征。 4、探究输注Anti-B7-H3-UCAR-T细胞受试者的血清细胞因子特征。 5、探索潜在的可预测Anti-B7-H3-UCAR-T有效性和安全性的生物标志物。

Objectives of Study：

I. Primary Research objectives: 1. Evaluation of the clinical safety and tolerability of Anti-B7-H3-UCAR-T for treating relapsed or refractory bone and soft tissue sarcomas. II. Secondary Research objectives: 1. Preliminary evaluation of the clinical effectiveness of Anti-B7-H3-UCAR-T for treating relapsed or refractory bone and soft tissue sarcomas. 2. Preliminary evaluation of the pharmacokinetic profile of Anti-B7-H3-UCAR-T in subjects with relapsed or refractory bone or soft tissue sarcomas. 3. Preliminary evaluation of the pharmacokinetic profile of Anti-B7-H3-UCAR-T for treating subjects with relapsed or refractory bone or soft tissue sarcomas. 4. Exploration of the serum cytokine profile in subjects infused with Anti-B7-H3-UCAR-T cells. 5. Exploration of potential biomarkers that may predict the efficacy and safety of Anti-B7-H3-UCAR-T.

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

Patients must meet the following criteria to participate in this study:
(1) Patients have fully understood this study and voluntarily signed the Informed Consent Form (ICF), and they are willing to comply and cooperate with the follow-up.
(2) Age ≥10 years old, gender is not limited;
(3) Patients with histologically confirmed relapsed/refractory bone and soft tissue sarcomas that have failed first-line and/or second-line treatment (disease progression or recurrence or intolerable) or lack of effective therapies;
(4) At least one measurable lesion according to RECIST (V1.1) criteria. The puncture biopsy before and after drug administration as judged by the investigator based on patient condition;
(5) Eastern Cooperative Oncology Group (ECOG) physical status score: 0-2;
(6) Estimated life expectancy is greater than 3 months;
(7) Patients are required to undergo lesion detection before enrollment (immunofluorescence testing of fresh tumor tissue samples obtained by puncture biopsy, or immunohistochemistry/immunofluorescence staining of surgically resected tissue wax-ups within the last 1 year), and the expression of B7-H3 in their tumor cells is required to be more 70%;
(8) Major organ function needs to meet the following criteria prior to treatment (no transfusion of blood, erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF), etc., within 14 days prior to the screening period examination): 
Hematology: 
	Absolute neutrophil count >= 1.0 × 10^9 /L. 
	Platelets >= 75 × 10^9 /L. 
	Hemoglobin >= 80 g/L. 
Renal function: 
	Serum creatinine <= 1.5 × upper limit of normal range (ULN), creatinine clearance (Cockcroft and Gaul) > 30 mL/min, except for acute CrCl decline caused by the disease itself.
Liver function: 
	Total bilirubin <= 1.5 × ULN (patients with liver metastases, bile duct obstruction, or confirmed Gilbert's syndrome: <= 3 × ULN).
	Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 2.5 × ULN (patients with liver metastases: <= 5 × ULN). 
Coagulation function: 
	International normalized ratio (INR) or prothrombin time (PT) <= 1.5 × ULN; 
	Activated partial thromboplastin time (APTT) <= 1.5 × ULN; 
(9) Non-surgically sterilized or female subjects of childbearing age, and male subjects whose partner is a female of childbearing age, are required to use contraception [e.g., intrauterine device (IUD), birth control pills, or condoms] during the study treatment period and for 6 months after the end of the treatment period of the study. Female patients of childbearing potential must have a negative blood pregnancy test result within 7 days prior to study entry; and must not be lactating.

排除标准：

符合以下任何一条排除标准的受试者将被排除：（1）有严重的药物过敏史或过敏体质者；（2）存在或怀疑无法控制的或需要治疗的真菌、细菌、病毒或其他感染；（3）终末期肾功能衰竭的受试者；（4）有精神疾病和严重认知功能障碍；（5）入选前1个月内参加过其他临床试验者；（6）曾经接受过靶向任何靶点的CAR-T治疗的患者；（7）曾经接受过任何一种靶向B7-H3治疗的患者；（8）既往患有其他恶性肿瘤，但除以下情况外：已被治愈的或5 年内持续为无病生存状态的局部可治愈的恶性肿瘤；（9）自身免疫性疾病（Autoimmune diseases，ADs）导致或非ADs导致的中枢神经系统疾病者（包括癫痫、精神病、器质性脑病综合症、脑血管意外、脑炎、中枢神经系统血管炎）；（10）在签署ICF前2周内接受过化疗、放疗、生物治疗、内分泌治疗、靶向治疗、免疫治疗等抗肿瘤治疗，或其它未上市的临床研究药物治疗；（11）在首次使用研究药物前4周内进行过大型外科手术或尚未从之前任何有创性操作中完全恢复；（12）在签署ICF前1周内接受过全身使用的糖皮质激素（强的松>10 mg/天或等效剂量的同类药物）或其他免疫抑制剂治疗［除以下情况外：使用局部、眼部、关节腔内、鼻内和吸入型糖皮质激素治疗；短期使用糖皮质激素进行预防治疗（例如预防造影剂过敏）］；（13）入选前2周内有感染，且需要全身（口服或静脉注射）抗感染治疗（无并发症的尿路感染或上呼吸道感染除外）；（14）在首次使用研究药物前4周内使用过灭活疫苗或减毒活疫苗或新型冠状病毒疫苗；（15）有严重的心血管疾病史，如有严重的心脏节律或传导异常（需要临床干预的室性心律失常、Ⅱ-Ⅲ度房室传导阻滞等）、首次给药前6个月内有心肌梗死、不稳定型心绞痛、心力衰竭、纽约心脏病学会（NYHA）分级为Ⅱ级及以上、冠状动脉架桥外科病史；筛选期左室射血分数（Left ventricular ejection fraction，LVEF）< 55%者、男性 QTcF > 450 msec 或女性QTcF > 470 msec 等；（16）既往抗肿瘤治疗的不良反应尚未恢复到CTCAE V5.0等级评价≤1级（脱发等研究者判断无安全风险的毒性除外）；（17）具有临床症状的中枢神经系统转移或脑膜转移，或有其他证据表明患者中枢神经系统转移或脑膜转移灶尚未控制，经研究者判断不适合入选；（18）有胸/腹水或心包积液并伴有临床症状或需要对症处理者；（19）有严重肺部疾病史的患者，如间质性肺疾病和/或肺炎，或肺动脉高压，或既往存在肺功能严重受损；（20）甲状腺功能异常患者，但如果经药物控制后甲状腺功能正常，则允许入选；（21）有自身免疫性疾病史（除外结节性硬化）、免疫缺陷病史，包括人类免疫缺陷病毒（Human immunodeficiency virus，HIV）检测阳性，或患有其他获得性、先天性免疫缺陷疾病，或有器官移植史；（22）活动性乙型肝炎、活动性丙型肝炎病毒感染或活动性梅毒感染： • 活动性乙型肝炎：乙肝表面抗原（Hepatitis B surface antigen，HBsAg）阳性，且HBV-DNA定量滴度高于正常范围上限值则排除；若HBsAg阳性，且外周血HBV-DNA 低于正常范围上限值，同时研究者认为受试者慢性乙肝处于稳定期且不会增加受试者风险，则受试者有资格入选； • 活动性丙型肝炎：抗丙型肝炎病毒（Hepatitis C virus， HCV）抗体阳性且HCV RNA 阳性； • 活动性梅毒感染：梅毒螺旋体抗体（RPR 或 TRUST法检测）阳性或存在需要系统性治疗的梅毒感染；（23）怀孕或打算孕育的女性；（24）经研究者判断认为有严重的危害患者安全、影响患者完成研究的伴随疾病（如不可控的高血压、活动性胃肠道出血等）或存在其他原因而不适合参加本临床研究者。

Exclusion criteria：

Patients meeting any of the following exclusion criteria will be excluded: (1) Patients with a history of severe drug allergies or sensitivities. (2) Patients with the presence or suspicion of fungal, bacterial, viral, or other infections that are uncontrollable or require treatment. (3) Patients with end-stage renal failure. (4) Patients who have mental illness and severe cognitive impairment. (5) Patients who have participated in another clinical trial within 1 month prior to enrollment. (6) Patients who have previously received CAR-T therapy targeting any target. (7) Patients who have received any kind of treatment targeting B7-H3. (8) Patients with another malignancy are excluded, except for those with a locally curable malignancy that has been cured or has persisted in a disease-free state for five years. (9) People with autoimmune diseases (ADs) or non-ADs that cause central nervous system disorders, including epilepsy, psychosis, organic encephalopathy syndromes, cerebrovascular accidents, encephalitis, and central nervous system vasculitis. (10) Patients received antitumor therapy, such as chemotherapy, radiotherapy, biotherapy, endocrine therapy, targeted therapy, immunotherapy, or other investigational drug therapy not listed, within two weeks prior to signing the informed consent form. (11) Patients who have undergone major surgery or have not fully recovered from any previous invasive operation within four weeks prior to receiving the first dose of the study drug. (12) Patients were treated with systemic corticosteroids (prednisone at a dose greater than 10 mg/day, or an equivalent dose of another corticosteroid) or other immunosuppressive therapy within one week prior to signing the Informed Consent Form (ICF), except for topical, ocular, intra-articular, intranasal, or inhaled corticosteroid therapy, or short-term prophylactic corticosteroid use (e.g., to prevent contrast media allergy). (13) Patients had an infection within two weeks prior to enrollment that required systemic (oral or intravenous) anti-infective therapy, except for uncomplicated urinary or respiratory tract infections. (14) Patients has received an inactivated or live-attenuated vaccine, or a novel coronavirus vaccine, within four weeks prior to receiving the first dose of the study drug. (15) Patients with a history of severe cardiovascular disease, such as severe cardiac rhythm or conduction abnormalities (e.g., ventricular arrhythmias requiring clinical intervention or second- or third-degree atrioventricular block), myocardial infarction, unstable angina pectoris, or heart failure classified as NYHA class II or higher within the six months prior to the first dose of the study medication. Patients with a left ventricular ejection fraction (LVEF) of less than 55% and a QTcF of greater than 450 milliseconds in men or greater than 470 milliseconds in women during the screening period. (16) Adverse effects of prior antitumor therapy that have not recovered to a CTCAE V5.0 grade rating of <= 1 (except for toxicities such as alopecia, etc., which are judged by the investigator to pose no safety risk). (17) Patients with clinically symptomatic central nervous system metastases or meningeal metastases, or other evidence that the patient's central nervous system metastases or meningeal metastases have not yet been controlled and are judged by the investigator to be unsuitable for enrollment. (18) Those with pleural/abdominal fluid or pericardial effusion with clinical symptoms or requiring symptomatic management. (19) Patients with a history of severe lung disease, such as interstitial lung disease and/or pneumonia, or pulmonary hypertension, or a history of severely impaired lung function. (20) Patients with abnormal thyroid function, but allowed to be enrolled if thyroid function is normal after pharmacologic control. (21) Patients with a history of an autoimmune disease (except tuberous sclerosis), an immunodeficiency disease (including a positive results of HIV test), or other acquired or congenital immunodeficiency diseases; or a history of organ transplantation. (22) Active hepatitis B, active hepatitis C virus infection, or active syphilis infection: -Active hepatitis B: Patients who are positive for the Hepatitis B surface antigen (HBsAg) and have a quantitative hepatitis B virus (HBV) DNA titer that is higher than the upper limit of the normal range. Alternatively, patients are eligible for enrollment if they are HBsAg positive and their peripheral blood HBV-DNA is below the upper limit of the normal range and the investigator believes that their chronic hepatitis B is stable and does not increase their risk. (23) Females who are pregnant or intend to become pregnant. (24) Individuals who, according to the investigator, have a serious underlying medical condition (e.g., uncontrolled hypertension, active gastrointestinal bleeding, etc.) that endangers the patient's safety, hinders the patient's ability to complete the study, or for whom there is another reason that makes them unsuitable for participation in this clinical study.

研究实施时间：

Study execute time：

从 From 2025-10-31 00:00:00至 To 2028-10-31 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2025-11-01 00:00:00 至 To 2028-09-01 00:00:00

干预措施：

Interventions：

组别：	A组	样本量：	6
Group：	Group A	Sample size：	6
干预措施：	按照1E6/kgBW的剂量对受试者进行静脉输注Anti-B7-H3-UCAR-T细胞。	干预措施代码：
Intervention：	Subjects were infused intravenously with Anti-B7-H3-UCAR-T cells at a dose of 1E6/kgBW.	Intervention code：

组别：	B组	样本量：	6
Group：	Group B	Sample size：	6
干预措施：	按照5E6/kgBW的剂量对受试者进行静脉输注Anti-B7-H3-UCAR-T细胞。	干预措施代码：
Intervention：	Subjects were infused intravenously with Anti-B7-H3-UCAR-T cells at a dose of 5E6/kgBW.	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	上海	市(区县)：
Country：	China	Province：	Shanghai	City：
单位(医院)：	上海长征医院	单位级别：	三甲
Institution hospital：	Shanghai Changzheng Hospital	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	安全性	指标类型：	主要指标
Outcome：	Safety	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：	objective response rate, 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：	疾病控制率	指标类型：	次要指标
Outcome：	DCR	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	缓解持续时间	指标类型：	次要指标
Outcome：	disease control rate, DOR	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	无进展生存期	指标类型：	次要指标
Outcome：	progression-free survival, PFS	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：	Overall survival, OS	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：	肿瘤组织	组织：
Sample Name：	Tumor tissue	Tissue：
人体标本去向	使用后保存	说明
Fate of sample：	Preservation after use	Note：

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	10	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）：

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：
Blinding：

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：	无
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	None
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：	2025-09-04 08:39:54