ChiCTR2100053884 版本V1.4 版本创建时间2022/10/30 13:06:45 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：

ChiCTR2100053884 

最近更新日期：

Date of Last Refreshed on：

2022-05-29 15:25:48 

注册时间：

Date of Registration：

2021-12-02 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

抗CEA/CD30 CAR-T （anti CEA/CD30 CAR-T）细胞注射液治疗CEA+局部晚期和/或转移性实体瘤患者的安全性和有效性的探索性临床研究

Public title：

An exploratory clinical study on the safety and efficacy of anti-CEA/CD30 CAR-T (anti-CEA/CD30 CAR-T) cell injection in the treatment of CEA+ patients with locally advanced and/or metastatic solid tumors

注册题目简写：

English Acronym：

研究课题的正式科学名称：

抗CEA/CD30 CAR-T （anti CEA/CD30 CAR-T）细胞注射液治疗CEA+局部晚期和/或转移性实体瘤患者的安全性和有效性的探索性临床研究

Scientific title：

An exploratory clinical study on the safety and efficacy of anti-CEA/CD30 CAR-T (anti-CEA/CD30 CAR-T) cell injection in the treatment of CEA+ patients with locally advanced and/or metastatic solid tumors

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：

钱羽 

研究负责人：

胡胜 

Applicant：

Qian Yu 

Study leader：

Hu Sheng 

申请注册联系人电话：

Applicant telephone：

+86 13545906716

研究负责人电话：

Study leader's telephone：

+86 15377602179

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：

173653835@qq.com

研究负责人电子邮件：

Study leader's E-mail：

ehusmn@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：

湖北省武汉市洪山区卓刀泉南路116号

研究负责人通讯地址：

湖北省武汉市洪山区卓刀泉南路116号

Applicant address：

116 Zhuodaoquan Road South, Hongshan District, Wuhan, Hubei

Study leader's address：

116 Zhuodaoquan Road South, Hongshan District, Wuhan, Hubei

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：

湖北省肿瘤医院

Applicant's institution：

Hubei Cancer 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/Yes

Approved by ethic committee：

Yes

伦理委员会批件文号：

Approved No. of ethic committee：

2021-159-002

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：

湖北省肿瘤医院伦理委员会

Name of the ethic committee：

Ethics Committee of Hubei Cancer Hospital

伦理委员会批准日期：

Date of approved by ethic committee：

2021-09-27 00:00:00

伦理委员会联系人：

施露露

Contact Name of the ethic committee：

Shi Lulu

伦理委员会联系地址：

湖北省武汉市洪山区卓刀泉南路116号

Contact Address of the ethic committee：

116 Zhuodaoquan Road South, Hongshan District, Wuhan, Hubei

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 27 87671663

伦理委员会联系人邮箱：

Contact email of the ethic committee：

hbchlunli@163.com

研究实施负责（组长）单位：

湖北省肿瘤医院

Primary sponsor：

Hubei Cancer Hospital

研究实施负责（组长）单位地址：

湖北省武汉市洪山区卓刀泉南路116号

Primary sponsor's address：

116 Zhuodaoquan Road South, Hongshan District, Wuhan, Hubei

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

湖北

市(区县)：

武汉

Country：

China

Province：

Hubei

City：

Wuhan

单位(医院)：

湖北省肿瘤医院

具体地址：

洪山区卓刀泉南路116号

Institution
hospital：

Hubei Cancer Hospital

Address：

116 Zhuodaoquan Road South, Hongshan District

经费或物资来源：

上海首歌生物科技有限公司

Source(s) of funding：

Shanghai First Song Therapeutics Co., LTD.

Target disease：

CEA+ Advanced Metastatic Solid Tumor

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：

1.主要目的： （1）评估anti CEA/CD30 CAR-T细胞治疗CEA+局部晚期和/或转移性实体瘤患者的安全性和耐受性。 （2）确定anti CEA/CD30 CAR-T细胞治疗的剂量限制性毒性（DLT），最大耐受剂量（MTD）。 2.次要目的： （1）初步评价anti CEA/CD30 CAR-T细胞治疗CEA+局部晚期和/或转移性实体瘤患者的疗效。 （2）评估anti CEA/CD30 CAR-T细胞的代谢动力学特征。  

Objectives of Study：

1. Main purpose: (1) To evaluate the safety and tolerability of anti-CEA/CD30 CAR-T cells in patients with CEA+ locally advanced and/or metastatic solid tumors. (2) To determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of anti-CEA/CD30 CAR-T cell therapy. 2. Secondary purpose: (1) Preliminary evaluation of the efficacy of anti-CEA/CD30 CAR-T cells in the treatment of CEA+ patients with locally advanced and/or metastatic solid tumors. (2) To evaluate the metabolic kinetics of anti-CEA/CD30 CAR-T cells.

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.理解并签署知情同意书，自愿参加临床研究 ；
2.年龄 18-70岁，性别不限 ；
3.要求有肿瘤组织中胞浆和/或膜性高CEA表达的局部晚期和/或转移性实体肿瘤的受试者（无可供检测的存档肿瘤组织的参与者必须有可活检的病灶）；
4.参与者处于肿瘤复发或者肿瘤持续/难治状态，之前接受过至少2线以上的系统性标准治疗（SOC）后疾病进展，对SOC不耐受，或对SOC不适应；难以接受标准（治疗意图）手术、放疗，目前尚无有效的治疗方法。无手术指征/术后复发的晚期/转移性胰腺癌，1线标准治疗失败或拒绝标准治疗的胰腺癌患者，均可以入组本试验；
治疗失败的定义：
（1） 治疗过程中疾病进展或治疗结束后肿瘤复发转移，或者出现不可耐受的毒性；
（2）进展期疾病的每一线的治疗包括用药时间≥1个周期或者更长时间的一种或多种化疗药物；允许前期进行辅助/新辅助治疗，如果辅助/新辅助治疗期间或者完成后≤24周内出现了肿瘤复发转移，则认为前期的辅助/新辅助治疗时一个针对进展期疾病的一线全身化疗；
5.根据RECIST v1.1，至少有一个可测量病灶；
6.预期生存期≥12周；
7.患者的东部肿瘤协作组（ECOG）体力状态评分必须是0-2分；
8.除脱发（任何级别）和2级周围神经病外，任何先前放疗、化疗或外科手术导致的所有机型毒性作用必须解决到≤1级或恢复到基线；
9.有足够的血液学功能，且筛选血液评估前7天未接受过细胞生长因子长效集落刺激因子G-CSF/PEG-CSF）需要间隔2周，重组红细胞生成素除外：
（1）嗜中性粒细胞绝对值 ≥ 1.0×10^9/L；
（2）血红蛋白 ≥ 80 g/L（在 14天内无红细胞输注的情况下）；
（3）血小板 ≥ 75×10^9/L；
（4）绝对淋巴细胞 (ALC) ≥ 0.5×10^9/L；
10.有足够的肝功能：血清总胆红素 ≤ 1.5×正常值上限（ULN）（排除吉尔伯特综合征），天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）≤ 2.5×ULN；如果有肝转移，允许其AST、ALT ≤ 5×ULN）；
11.有足够的肾功能：肌酐 ＜ 1.5×ULN且内生肌酐清除率 ≥ 60 mL/Min（采用Cockcroft Gault公式）；
12.没有证据显示受试者在静息时呼吸困难，并且在呼吸室内空气时的脉搏血样测定值 ＞ 90%；
13.具备足够的静脉通路（进行单采），且无其他血细胞分离禁忌症；
14.育龄期妇女血清妊娠试验必须为阴性。所有受试者必须同意自签署知情同意书开始至研究药物末次给药后6个月内同时采取有效的避孕方法。

Inclusion criteria

1. Understand and sign the informed consent form and voluntarily participate in clinical research;
2. Aged 18-70 years, gender is not limited;
3. Subjects with locally advanced and/or metastatic solid tumors with cytoplasmic and/or membranous high CEA expression in tumor tissue are required (participants without detectable archived tumor tissue must have biopsiable lesions) ;
4. The subjects is in a tumor recurrence or tumor persistent/refractory state, and has received at least 2 or more lines of systemic standard therapy (SOC) before with disease progression, is intolerant to SOC, or is not adapted to SOC; It is difficult to accept standard (treatment intent) surgery and radiotherapy, and there is currently no effective treatment. Advanced/metastatic pancreatic cancer with no indication for surgery/postoperative recurrence, pancreatic cancer patients who failed the first-line standard treatment or refused standard treatment, can be enrolled in this trial;
Definition of Treatment Failure:
(1) Disease progression during treatment or tumor recurrence and metastasis after treatment, or intolerable toxicity;
(2) Each line of treatment for advanced disease includes one or more chemotherapy drugs for >=1 cycle or longer; early adjuvant/neoadjuvant therapy is allowed. If tumor recurrence and metastasis occur during adjuvant/neoadjuvant therapy or within <=24 weeks after completion of adjuvant/neoadjuvant therapy, the adjuvant/neoadjuvant therapy is considered as a first-line systemic chemotherapy for advanced disease;
5. At least one measurable lesion according to RECIST v1.1;
6. Expected survival period >= 12 weeks;
7. The patient's Eastern Cooperative Oncology Group (ECOG) performance status score must be 0-2;
8. All types of toxic effects from any prior radiotherapy, chemotherapy, or surgery, except alopecia (any grade) and grade 2 peripheral neuropathy, must resolve to <= grade 1 or return to baseline;
9. Have sufficient hematological function, and have not received cell growth factor long-acting colony-stimulating factor (G-CSF/PEG-CSF) 7 days before the screening blood assessment, requiring an interval of 2 weeks, except for recombinant erythropoietin:
(1) The absolute value of neutrophils is >= 1.0x10^9/L;
(2) Hemoglobin >= 80 g/L (without red blood cell transfusion within 14 days);
(3) Platelets >= 75x10^9/L;
(4) Absolute lymphocytes (ALC) >= 0.5x10^9/L;
10. Sufficient liver function: serum total bilirubin <= 1.5 x upper limit of normal (ULN) (excluding Gilbert syndrome), aspartate aminotransferase (AST), alanine aminotransferase (ALT) <= 2.5xULN; if there is liver metastasis, AST, ALT <= 5xULN are allowed);
11. Sufficient renal function: creatinine < 1.5xULN and endogenous creatinine clearance >= 60 mL/Min (using Cockcroft Gault formula);
12. There is no evidence that the subject has difficulty breathing at rest, and the measured value of the pulse blood sample when breathing room air is > 90%;
13. Have sufficient venous access (for apheresis), and no other contraindications for blood cell separation;
14. The serum pregnancy test for women of childbearing age must be negative. All subjects must agree to take effective contraceptive methods at the same time from signing the informed consent to 6 months after the last dose of the study drug.

排除标准：

1.既往使用过任何CAR-T细胞产品或其他基因修饰的T细胞疗法者；
2.既往有过异体干细胞或实体器官移植史或正在等待器官移植的患者；
3.急性或不受控制的活动性感染，包括但不限于活动性结核；
4.乙型（乙肝病毒表面抗原阳性和/或乙型肝炎核心抗体阳性且乙肝DNA＞10^3拷贝/mL）和丙型肝炎（丙肝抗体检测阳性）；梅毒、人类免疫缺陷病（HIV）感染（HIV阳性）；
5.低钠和 /或低钾血症患者，血钠 ＜ 125 mmol/L和/或血钾 ＜ 3.5 mmol/L（参加研究前可补钠和/或钾，使血钠和/或血钾恢复到此水平以上除外）；
6.关键部位（如脊柱旁、气管旁）有2厘米病灶的受试者，预计可能治疗过程中，肿瘤肿胀导致严重并发症；
7.影像学检查结果，肝脏被肿瘤取代比例 ≥ 50%，或门脉主干癌栓（占据血管管径 ≥ 50%），或癌栓侵犯肠系膜静脉/下腔静脉；
8.目前存在有临床意义的胸水和腹水，定义为：需要非药物干预（例如穿刺术）或增加药物干预以维持症状控制的胸水和腹水；
9.单采前14天内接受过持续全身性类固醇药物（泼尼松 ＞ 5mg/天或相当剂量的其他激素）或者其他免疫抑制剂的患者，但近期或者目前使用吸入性类固醇除外；
10.单采前2周或者5个半衰期内接受全身性化疗，或者既往抗肿瘤治疗的毒性反应尚未恢复（＞ CTCAE 5.0版1级），但脱发和色素沉着除外；
11. 单采和清淋预处理前，既往接受过抗体治疗，且在4周内；
12.在单采和清淋预处理前，既往接受过任何抑制性/刺激性免疫检查点分子治疗（抗PD-1/PD-L1单克隆抗体、OX40激动剂、4-1BB激动剂）），且在3个半衰期内；
13.在单采前28天内使用过免疫刺激或免疫抑制治疗（如干扰素-α、干扰素-β、IL-2、依那西普、英夫利昔单抗、他克莫司、环孢素或麦考酚酸）；
14.在单采前和输注前72小时内使用短效靶向治疗（如络氨酸激酶抑制剂）；
15.在单采前的最后28天内进行放射治疗，但有限局部姑息放疗除外；
16.既往或现在同时患有其他恶性肿瘤（皮肤基底细胞癌、乳腺/宫颈原位癌和其他在过去五年内没有治疗也得到有效控制的恶性肿瘤除外）；
17.既往有种属神经系统（CNS）原发或转移肿瘤包括脑膜转移的病史或临床证据的受试者，除非既往接受过治疗脑转移，目前无症状，且在筛查前最后14天不需要类固醇或酶诱导抗癫痫药治疗；
18.现有其他任何中枢神经系统疾病的患者（如癫痫发作、脑血管缺血/出血、痴呆等）；
19.有不受控制的高血压，不稳定型心绞痛，纽约心脏协会呈III级或更高级别的充血性心力衰竭，心脏射血分数低于50%，或ECG检查有显著异常，需要治疗的严重心率失常以及在开始研究治疗前6个月内有心肌梗死病史；
20.单采前（入组时）存在严重呼吸系统疾病者，如间质性肺病、 活动性肺结核等研究者认为不适宜入组；
21.根据研究者判断，任何严重的或不能控制的系统性疾病，系统性合并症、其他严重并发疾病（如嗜血细胞综合征等）、肿瘤特殊情况可能使患者不适合进入本研究或影响方案依从性，或对研究药物安全性、毒性、有效性的正确评估产生显著干扰；
22.单采前4周内进行过外科大手术（大手术定义参照《医疗技术临床应用管理办法》中规定的3级和4级手术）；或尚未从之前的任何有创性操作中完全恢复；
23.给药前1个月内参加过其他干预性临床试验者；
24.已经妊娠、试验期间准备妊娠、或正在哺乳的女性；
25.在研究期间，育龄女性及有生育能力男性不愿或无法采用可靠的避孕方式；
26.参与该研究计划和执行的人员 。

Exclusion criteria：

1. Those who have previously used any CAR-T cell product or other genetically modified T cell therapy;
2. Patients who have a history of allogeneic stem cell or solid organ transplantation or are waiting for organ transplantation;
3. Acute or uncontrolled active infection, including but not limited to active tuberculosis;
4. Hepatitis B (positive for hepatitis B virus surface antigen and/or positive for hepatitis B core antibody and hepatitis B DNA>10^3 copies/mL) and hepatitis C (positive for hepatitis C antibody test); syphilis, human immunodeficiency (HIV) infection (HIV positive);
5. Patients with hyponatremia and/or hypokalemia, serum sodium < 125 mmol/L and/or serum potassium < 3.5 mmol/L (except for sodium and/or potassium supplementation before participating in the study to restore serum sodium and/or potassium to above this level);
6. Patients with 2 cm lesions in key parts (such as paraspinal, paratracheal), it is expected that during the course of treatment, tumor swelling may lead to serious complications;
7. Imaging examination results, the proportion of liver is replaced by tumor >= 50%, or the tumor thrombus of the main portal vein (occupying >= 50% of the vessel diameter), or the tumor thrombus invades the mesenteric vein/inferior vena cava;
8. There is currently clinically significant pleural effusion and ascites, defined as: pleural effusion and ascites requiring non-drug intervention (such as paracentesis) or increased drug intervention to maintain symptom control;
9. Patients who have received continuous systemic steroids (prednisone > 5mg/day or equivalent doses of other hormones) or other immunosuppressants within 14 days before apheresis, except for recent or current use of inhaled steroids;
10. Received systemic chemotherapy within 2 weeks or 5 half-lives before apheresis, or the toxicity of previous anti-tumor therapy has not recovered (> CTCAE version 5.0 grade 1), except for alopecia and pigmentation;
11. Before apheresis and lymphore pretreatment, received antibody therapy in the past, and within 4 weeks;
12. Previously received any inhibitory/stimulatory immune checkpoint molecular therapy (anti-PD-1/PD-L1 monoclonal antibody, OX40 agonist, 4-1BB agonist) prior to apheresis and lymphadenectomy , and within 3 half-lives;
13. Use of immunostimulatory or immunosuppressive therapy within 28 days before apheresis (such as interferon-alpha, interferon-beta, IL-2, etanercept, infliximab, tacrolimus, cyclosporine, or mycophenolic acid);
14. Use short-acting targeted therapy (such as tyrosine kinase inhibitors) within 72 hours before apheresis and infusion;
15. Radiation therapy within the last 28 days before apheresis, except for limited local palliative radiation therapy;
16. Past or present with other malignant tumors (except skin basal cell carcinoma, breast/cervical carcinoma in situ and other malignant tumors that have been effectively controlled without treatment within the past five years);
17. Patients with previous history or clinical evidence of primary or metastatic tumors of the species nervous system (CNS) including meningeal metastasis, unless previously treated for brain metastases, currently asymptomatic, and not requiring steroid or enzyme-inducing antiepileptic drug therapy in the last 14 days prior to screening;
18. Patients with any other existing central nervous system diseases (such as epilepsy, cerebrovascular ischemia/bleeding, dementia, etc.);
19. Uncontrolled hypertension, unstable angina, congestive heart failure of New York Heart Association class III or higher, cardiac ejection fraction less than 50%, or significant abnormality in ECG examination, severe arrhythmia requiring treatment, and a history of myocardial infarction within 6 months prior to initiation of study treatment;
20. Those with severe respiratory diseases before apheresis (at the time of enrollment), such as interstitial lung disease, active pulmonary tuberculosis, etc., are considered inappropriate by the researchers;
21. According to the judgment of the investigator, any serious or uncontrollable systemic disease, systemic comorbidities, other serious concurrent diseases (such as hemophagocytic syndrome, etc.) and special tumor conditions may make patients unsuitable for entering this study or affect protocol compliance, or significantly interfere with the correct assessment of the safety, toxicity and efficacy of the study drug;
22. Major surgical operations have been performed within 4 weeks before apheresis (the definition of major surgery refers to the Class 3 and Class 4 surgeries specified in the Administrative Measures for Clinical Application of Medical Technology); or have not fully recovered from any previous invasive operations;
23. Those who have participated in other interventional clinical trials within 1 month before administration;
24. Patients who are already pregnant, plan to become pregnant during the test, or are breastfeeding;
25. During the study period, women of childbearing age and men with childbearing potential were unwilling or unable to use reliable contraceptive methods;
26. People involved in the planning and execution of the research.

研究实施时间：

Study execute time：

从 From 2022-01-01 00:00:00至 To 2025-01-01 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2022-01-01 00:00:00 至 To 2025-01-01 00:00:00  

干预措施：

Interventions：

组别：

治疗组

样本量：

12

Group：

Treatment group

Sample size：

干预措施：

输注anti CEA/CD30 CAR T细胞

干预措施代码：

Intervention：

Infusion of anti-CEA/CD30 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)：

 湖北 

市(区县)：

 武汉 

Country：

China 

Province：

Hubei 

City：

Wuhan 

单位(医院)：

湖北省肿瘤医院 

单位级别：

三级甲等 

Institution
hospital：

Hubei Cancer 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：

Objective Remission Rate (ORR)

Type：

Primary 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：

Disease Control Rate (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：

疗效持续时间

指标类型：

次要指标

Outcome：

Duration of Response (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：

指标中文名：

安全性指标

指标类型：

次要指标

Outcome：

Safety

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：

全血

组织：

Sample Name：

Whole 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：

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 岁 years
最大 Max age 70 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

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：

  2021-12-02 04:55:55