肿瘤细胞治疗研究
英文原题：Safety and Efficacy of Systemic Allogenic NK Cells in R/R Neuroblastoma
Safety and Efficacy of Systemic Allogenic NK Cells in R/R Neuroblastoma
⚠ 该试验的登记信息已有 18 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，评估异体 NK 细胞治疗神经母细胞瘤的安全性、可行性及初步疗效。当前状态：招募中。计划入组 10 例。试验地点：其他 · 德黑兰（共 1 个中心）。登记号：NCT06674265。
不限性别 · ≥ 2 Years 且 ≤ 16 Years
纳入标准： 1. 高危神经母细胞瘤，按儿童肿瘤协作组（COG）标准对标准诱导治疗耐药：符合INRG标准，已接受至少4个周期的多药诱导化疗，且对常规治疗无应答。 2. 自体外周血造血干细胞移植或强化治疗后有神经母细胞瘤复发或进展证据。 3. 预期生存期至少6个月。 4. 病理确诊神经母细胞瘤，和/或骨髓证实存在肿瘤细胞并伴尿儿茶酚胺升高。 5. 影像学存在可测量残留病灶，按Curie评分、MIBG或PET标准评估：其一，MRI或CT至少一个方向可测量病灶≥10 mm，且¹²³I-MIBG显像摄取阳性；或其二，¹⁸F-FDG PET-CT或PET-MRI显示摄取增高。 排除标准： 1. 骨髓功能不足：血小板计数>50,000/μL且不依赖输注（前1周未输注血小板）；ANC最高限值为500/μL；血红蛋白>10 g/dL。 2. 肝功能不足：血浆胆红素>ULN的1.5倍；SGPT（ALT）至少为ULN的3倍（ULN按45 U/L计）。 3. 肾功能不足：肌酐清除率或同位素估算GFR<70 mL/min/1.73 m²；或血浆肌酐>按年龄/性别确定的ULN的1.5倍。 4. 中枢神经系统功能不足：存在癫痫发作时不得入组；若癫痫不能通过抗惊厥药物良好控制，也不得入组。 5. 心血管功能不足：超声心动图短轴缩短率<27%，或超声心动图/门控核素显像测得射血分数<50%。 6. 肺功能不足：静息时呼吸困难、运动不耐受、长期需要氧疗，或临床需要进行脉搏血氧检测时室内空气下血氧饱和度<94%；存在胸腔或心包积液。 7. 有急症，无法耐受新的治疗。 8. 儿茶酚胺升高（>ULN的2倍），或仅有骨髓受累（骨髓为唯一可评估疾病且缺少病理报告确认）。 9. 入组前至少7天持续接受全身性类固醇（泼尼松等效剂量0.5 mg/kg/日）。 10. 入组前至少7天接受CYP3A4诱导剂或抑制剂。 11. 除神经母细胞瘤外还确诊其他恶性肿瘤。 12. 腹泻>2级（每天4–6次排便）。 13. 未在上述标准中列明、但会干扰研究或增加NK细胞治疗强度要求的重大疾病。 14. 同时参加其他临床试验。 15. 主要器官功能严重受损，包括肾、心、肝、神经、肺或胃肠道毒性>美国国家癌症研究所CTCAE 5.0版2级。 16. 无法遵守方案要求；或未取得患者监护人确认并签署的知情同意书。 17. 有HIV感染证据或HIV血清学阳性。
Inclusion Criteria:
1. High-risk neuroblastoma that is resistant to standard induction therapy based on COG (Children's Oncology Group) criteria (according to INRG criteria and having received at least 4 cycles of multi-drug induction chemotherapy, and not responding to conventional treatments).
2. Evidence of relapse or progression of neuroblastoma after autologous peripheral blood stem cell transplantation or aggressive therapy.
3. A minimum life expectancy of 6 months.
4. Patients must have a pathological diagnosis of neuroblastoma and/or confirmation of tumor cells in the bone marrow with increased urinary catecholamines.
5. Measurable residual disease based on imaging findings using Curie scoring or MIBG or PET imaging criteria (1: measurable tumor of at least 10 mm in one dimension on MRI or CT scan with positive uptake on I-123 MIBG scan ("MIBG avid") oOR 2): increased FDG uptake on 18F-FDG PET-CT or PET-MRI ("PET avid")).
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Exclusion Criteria:
1. Insufficient bone marrow function: Platelet count \> 50,000/µL, independent of transfusion (no platelet transfusion within one week). Absolute neutrophil count (ANC) maximum of 500 per microliter. Hemoglobin \> 10 grams per deciliter.
2. Insufficient liver function: Plasma bilirubin level more than 1.5 times the upper limit of normal (ULN). SGPT (ALT) at least three times the upper limit of normal (a level of 45 units per liter is considered the upper limit of normal).
3. Insufficient kidney function: Creatinine clearance or estimated radioisotope GFR \< 70 ml/min/1.73m². Plasma creatinine level more than 1.5 times the upper limit of normal based on age/gender.
4. Insufficient central nervous system function if seizures are present, entry into the study is not possible and if seizures are not well controlled with anticonvulsant drugs.
3- Insufficient cardiovascular function Shortening fraction \< 27% by ECHO OR Ejection fraction \< 50% by ECHO or gated radionuclide study.
4- Insufficient pulmonary function evidence of dyspnea at rest. Exercise intolerance. Chronic need for oxygen and room air pulse oximetry \< 94% if pulse oximetry evaluation is clinically indicated. Presence of current pleural or pericardial effusion.
5- Inability to tolerate new treatment due to emergency conditions. 6- Elevated catecholamines (more than twice the ULN) or sole involvement of bone marrow (bone marrow positive for NB as the only evaluable disease without confirmatory pathology report).
7- Receiving 0.5 mg/kg/day of systemic steroids (equivalent to prednisone) for at least 7 days before enrollment.
8- Receiving CYP3A4 inducers or inhibitors at least 7 days before study enrollment.
9- Diagnosis of any other malignancy alongside the diagnosis of neuroblastoma. 10- Diarrhea \> Grade 2 (4 to 6 stools per day). 11- Significant illness not covered by exclusion criteria but interfering with the study process or increasing the intensity of treatment with NK cells.
12- Participation in another clinical trial. 13- Severe impairment of major organ functions, such as renal, cardiac, hepatic, neurological, pulmonary, or gastrointestinal toxicity above Grade 2 according to the National Cancer Institute's Common Terminology Criteria for Adverse Events version 5.0 (CTC v5.0).
14- Inability to comply with protocol requirements. 15- Lack of confirmed and signed consent by the patient's guardians. 16- Evidence of HIV disease (Human Immunodeficiency Virus) or positive serology for HIV.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：NK Cell Infusion Safety · The safety of the treatment is assessed using the Common Terminology Criteria for Adverse Events (CTCAE) checklist. · After each injection to next injection and 2 weeks after last injection
次要终点：Response rate comparison between control and intervention groups
复发/难治性神经母细胞瘤患者在化疗疗程间歇期接受3–5次异体NK细胞全身注射。
不输注细胞，仅接受常规治疗。
本临床试验旨在评估异体自然杀伤（NK）细胞全身注射治疗复发/难治性高危神经母细胞瘤患者的安全性和疗效。研究将NK细胞治疗组与仅接受常规治疗的对照组比较，以判断该治疗是否安全、有效。
The goal of this clinical trial is to assess safety and efficacy of systemic injection of allogenic NK cells in patients with refractory/recurrent high-risk neuroblastoma. Is the injection of allogenic nk cells safe in patients with R/R high-risk neuroblastoma? Is the injection of allogenic nk cells effective in patients with R/R high-risk neuroblastoma? We will compare the NK cell administration group with a control group that receives conventional treatment to determine whether the intervention is safe and effective
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