肿瘤细胞治疗研究
英文原题：Safety and Efficacy Study for DC Vaccine in Recurrent or Progressive High-grade Gliomas
⚠ 该试验的登记信息已有 20 个月未更新， 页面上显示的「招募中」可能已经失效。联系研究中心之前，建议先到 ClinicalTrials.gov 核对登记原文的最新状态与联系方式。
这是一项 I 期注册临床试验，评估树突状细胞治疗胶质瘤的安全性、可行性及初步疗效。当前状态：招募中。计划入组 12 例。试验地点：中国 · 北京（共 1 个中心，其中中国 1 个）。登记号：NCT06253234。
不限性别 · ≥ 18 Years 且 ≤ 75 Years
纳入标准：
* 受试者须符合以下全部条件：
1. 年龄18至75岁（含18岁和75岁）。
2. 经组织学或细胞学确诊为WHO III–IV级胶质瘤，且标准治疗后复发或进展。
3. 允许在采样后的准备期接受桥接治疗，但须在首次治疗前至少7天或5个药物半衰期（以较长者为准）停药。
4. 东部肿瘤协作组（ECOG）体能状态评分为0或2。
5. 实验室检查显示造血及器官功能符合要求：
血小板（PLT）≥90×10^9/L；中性粒细胞绝对计数（ANC）≥1.5×10^9/L；血红蛋白（HGB）≥90 g/L；血清丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）≤正常值上限（ULN）的2.5倍；总胆红素（TBIL）≤ULN的2.5倍；白蛋白（ALB）≥3 g/dl；肌酐清除率（CrCl）≥45 mL/min，或血清肌酐≤ULN的1.5倍；国际标准化比值（INR）及活化部分凝血活酶时间（APTT）≤ULN的1.5倍；脂肪酶≤ULN的1.5倍；淀粉酶≤ULN的1.5倍；碱性磷酸酶（ALP）≤ULN的2.5倍。
6. 可通过肿瘤减灭手术或活检获取足量肿瘤及血液样本用于二代测序（NGS）；外周血单个核细胞功能正常。
7. 首次治疗前，任何急性且具有临床意义的治疗相关毒性（脱发除外）已缓解至≤1级。
8. 心功能：血流动力学稳定，左心室射血分数（LVEF）≥50%。
9. 有足够的静脉通路用于采集外周血单个核细胞（PBMC），且无相关禁忌。
10. 未经手术绝育的育龄期受试者须在研究期间采取避孕措施，并且妊娠试验阴性。
11. 预计生存期>3个月。
12. 自愿参加并签署知情同意书。
13. 根据健康状况和实验室评估，研究者认为受试者参加本临床试验的获益风险比合理。
14. 受试者须能够持续依从研究要求，积极参加随访，并在整个试验期间按要求到研究中心定期检查和评估。
排除标准：
* 符合以下任一条件者不得参加：
1. 首次治疗前4周内参加过其他药物试验、接受过合并抗肿瘤治疗（允许的桥接治疗除外）、在外周血单个核细胞采集前14天内接受过输血、促红细胞生成素（EPO）、粒细胞集落刺激因子（G-CSF）或粒细胞-巨噬细胞集落刺激因子（GM-CSF），或首次治疗前28天内接种过活病毒疫苗。
2. 首次治疗前6个月内接受过喜树碱缓释制剂植入手术。
3. 患有活动性自身免疫性疾病、长期使用免疫抑制治疗，或已知对鸡蛋过敏。
4. HIV或梅毒抗体阳性，或存在活动性乙型或丙型肝炎。
5. 首次治疗前30天内接受过全身免疫抑制治疗。
注：经与研究者协商并获得申办方批准后，可考虑短期全身免疫抑制治疗。此类受试者首次治疗前的洗脱期及其时长须与申办方协商确定。
允许使用：用于慢性阻塞性肺疾病（COPD）的吸入性糖皮质激素；用于直立性低血压的盐皮质激素（如氟氢可的松）；以及用于肾上腺功能不全的低剂量糖皮质激素补充治疗（泼尼松或等效药物≤10 mg/日）。
6. 有严重疫苗过敏史；首次治疗前28天内使用过减毒活疫苗；或预计在末次研究药物给药后6个月内需要接种减毒活疫苗。
7. 存在未控制的全身性疾病，包括心血管疾病、器官功能衰竭、糖尿病或控制不佳的高血压。
8. 患有无法控制的精神疾病，或有可能增加风险或干扰研究结果的重要病史。
9. 首次治疗前6个月内发生过血栓事件，除非筛选期间可以停用抗凝治疗。
10. 存在不可逆的电解质紊乱。
11. 首次治疗前1个月内发生严重感染、感染控制不佳，或过去一周内需要接受抗生素治疗（预防性使用除外）。
12. 妊娠或哺乳期。
13. 研究者认为可能导致研究提前终止的情况，例如不依从、需要同时治疗的其他严重疾病、严重实验室检查异常，或影响受试者安全及数据/样本采集的家庭或社会因素。
Inclusion Criteria:
* Participants must meet all the following criteria to be eligible:
1. Age from 18 to 75 years (including 18 and 75 years old).
2. Subjects with histologically or cytologically confirmed WHO grade III-IV gliomas experiencing recurrence or progression after standard treatment.
3. Bridging therapy is allowed during the preparatory period after sample collection, with discontinuation at least 7 days or 5 drug half-lives (whichever is longer) before the initial treatment.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 2.
5. Laboratory test results defining satisfactory hematological and organ function:
Platelets (PLT) ≥ 90 × 10\^9/L; Absolute Neutrophil Count (ANC) ≥ 1.5 × 10\^9/L; Haemoglobin (HGB) ≥ 90 g/L; Serum Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 2.5× ULN; Total Bilirubin (TBIL) ≤ 2.5 × ULN; Albumin (ALB) ≥ 3 g/dl; Creatinine clearance rate (CrCl) ≥ 45 mL/minute or Serum Creatinine ≤ 1.5 ×ULN; International Normalized Ratio (INR), Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN; Lipase ≤ 1.5 × ULN; Amylase ≤ 1.5 × ULN; Alkaline Phosphatase (ALP) ≤ 2.5 × ULN.
6. Adequate tumor and blood samples for NGS gene sequencing can be obtained through tumor reduction surgery or biopsy. Peripheral blood mononuclear cell function is normal.
7. Relief of any acute, clinically significant treatment-related toxicities (excluding alopecia) to ≤ Grade 1 before the first treatment.
8. Heart function: Stable hemodynamics, LVEF ≥ 50%.
9. Adequate venous access for PBMC collection, with no contraindications.
10. Non-surgically sterilized reproductive-age subjects must use contraception during the study and have a negative pregnancy test.
11. Expected survival period \> 3 months.
12. Voluntary participation, signed informed consent.
13. Based on health and lab assessments, the investigator sees favorable risk-benefit for the subject in the clinical trial.
14. Subjects must consistently comply, actively participate in follow-up visits, and undergo regular testing and evaluation at the research center throughout the trial.
Exclusion Criteria:
* Subjects meeting any of the following criteria are ineligible:
1. Recent participation in other drug trials, concurrent anti-tumor therapy (excluding allowed bridging therapy) within 4 weeks before initial treatment, had blood transfusions, EPO, G-CSF, or GM-CSF in the 14 days before peripheral blood mononuclear cell collection, or received live virus vaccinations within 28 days before the first treatment.
2. Subjects who had camptothecin sustained-release agent implantation surgery within 6 months before the initial treatment.
3. Active autoimmune diseases, prolonged use of immunosuppressive therapy, or known egg allergy.
4. Positive for HIV or syphilis antibodies, or active hepatitis B or C.
5. Recent systemic immunosuppressive treatment within 30 days before the initial treatment.
Note: Short-term, systemic immunosuppressive treatment may be considered in consultation with the investigator and sponsor approval. The washout period and its duration before the initial treatment will be decided in consultation with the sponsor for these patients.
Allowed: Inhaled glucocorticoids for COPD, salt corticosteroids (e.g., fludrocortisone) for orthostatic hypotension, and low-dose glucocorticoid supplements (≤10 mg/day prednisone or equivalent) for adrenal insufficiency.
6. Exclusion: Severe vaccine allergy history, use of attenuated live vaccines within 28 days before initial treatment, or anticipated need within 6 months after the last dose of the investigational drug.
7. Uncontrolled systemic diseases, including cardiovascular diseases, organ failure, diabetes, and poorly controlled hypertension.
8. Unmanageable mental illness or significant medical history that may increase risks or interfere with results.
9. Thrombotic events within the first 6 months before initial treatment, unless anticoagulation can be discontinued during the screening period.
10. Irreversible electrolyte imbalances.
11. Severe infection in the first month before initial treatment, poorly controlled infection, or requiring antibiotic treatment within the past week (excluding prophylactic use).
12. Pregnant or lactating subjects.
13. Factors judged by the investigator that may necessitate premature study termination, such as non-compliance, other severe diseases requiring concurrent treatment, severe laboratory abnormalities, or family/social factors affecting subject safety or data/sample collection.以上为辅助阅读译文。是否适合入组须由主治医生判断，最终以登记平台与研究者确认为准。
主要终点：AE and SAE · Evaluating the incidence rates of Adverse Events and Serious Adverse Events · Throughout the whole clinical trial, around 2 years.；DLT · Dose-limiting toxicity.Referencing the results of the exploratory clinical study of ZSNeo-DC1.1 injection, clinical trial outcomes of similar drugs, and the NCI CTCAE 5.0 toxicity assessment criteria to determine DLT. The observation period for DLT is set during the activation of the subject's anti-tumor immune response, from the first day of treatment until 21 days after the third injection. · 2 months
次要终点：Assessment of ORR (Objective Response Rate)；Assessment of DCR (Disease Control Rate)；Assessment of CBR (Clinical Benefit Rate)；Assessment of PFS (Progression Free Survival)；OS (Overall survival)
这是一项单中心、开放标签、多次给药的I期临床试验，旨在评估个体化树突状细胞注射剂ZSNeo-DC1.1用于标准治疗后复发或进展的WHO III–IV级胶质瘤受试者时的安全性、耐受性和初步疗效。受试者为复发后接受过手术切除的成年胶质母细胞瘤（GBM）患者。再次手术完成后，受试者将按计划接受自体树突状细胞（DC）疫苗治疗。该自体DC细胞未经基因修饰，将负载多种肿瘤新抗原肽后通过瘤内注射给药。注射3次后，研究者将评估受试者的耐受性和依从性。DLT观察期从首次注射开始，至第三次注射后21天结束，与抗肿瘤免疫反应激活期相对应。 预计入组约15例受试者。每次注射固定剂量为1×10^7个细胞，并采用A或B两种免疫接种方案。 试验分为两个阶段： 剂量确认阶段： 入组6例标准治疗后复发或进展的胶质瘤受试者。每位受试者接受6次ZSNeo-DC1.1皮下注射。采用标准“3+3”设计，在固定剂量下确认剂量并探索免疫接种方案A和B。 剂量扩展阶段： 至少入组6例标准治疗后复发或进展的胶质瘤受试者。每位受试者接受6次ZSNeo-DC1.1皮下注射，进一步研究该注射剂的安全性和初步疗效。
This is a single-center, open-label, multi-dose phase I clinical trial evaluating the safety, tolerability, and preliminary efficacy of ZSNeo-DC1.1, a personalized dendritic cell injection, in subjects with recurrent or progressive WHO grade III-IV gliomas post-standard treatment. The subjects are adult GBM patients who have undergone surgical resection for recurrence. After the completion of reoperation, subjects will receive autologous DC vaccine treatments as scheduled. The autologous genetic-modification-free DC cells will be loaded with multiple tumor neoantigen peptides and administered (i.h) to subjects. After 3 injections, the investigator will review subject's tolerance and compliance. The DLT observation period spans from the initial injection to 21 days after the third injection, aligning with the activation of anti-tumor immune response. About 15 subjects will be enrolled. The study utilizes a fixed dose of 1×10\^7 cells per injection and employs two immunization schedules A or B. The trial is conducted in two stages: Dose Confirmation Stage: Enrollment of six subjects with recurrent or progressive gliomas following standard treatment. Each subject receives six subcutaneous injections of ZSNeo-DC1.1. Utilization of a standard "3+3" design for fixed dose confirmation and exploration of immunization schedules A and B. Dose Expansion Stage: Enrollment of at least six subjects with recurrent or progressive gliomas post-standard treatment. Administration of six subcutaneous injections of ZSNeo-DC1.1 to each subject, further investigating the safety and preliminary efficacy of ZSNeo-DC1.1 injection.
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