肿瘤细胞治疗研究
英文原题：Haploidentical Donor Cytokine-Induced Memory-Like Natural Killer Cells (CIML-NK) for Relapsed & Refractory Neuroblastoma
这是一项 II 期注册临床试验，评估 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 20 例。试验地点：美国 · 辛辛那提（共 1 个中心）。登记号：NCT07635056。
不限性别 · ≥ 1 Year 且 ≤ 39 Years
纳入标准： * 入组研究时年龄1-39岁 * 经组织学证实诊断为神经母细胞瘤 * 根据儿童肿瘤协作组（COG）风险分类被归类为高危神经母细胞瘤，包括初诊时被归类为低危或中危、随后重新分类为高危疾病的患者 * 患有复发性或难治性疾病，包括以下至少一项： 1. 一线治疗完成后任何时间出现疾病复发 2. 标准诱导治疗后任何时间出现疾病进展 3. 原发性耐药或难治性疾病，定义为按照高危神经母细胞瘤方案或根据该方案接受至少四个周期的标准多药诱导化疗后，未能达到国际神经母细胞瘤疗效标准（INRC）所定义的完全缓解 * 患者必须在研究入组四周内记录有可评估疾病。可评估疾病必须包括以下至少一项： 1. MRI或CT扫描上可测量的肿瘤（至少一个维度>10 mm），且为MIBG、FDG或68Ga-DOTATATE亲和 2. 一个或多个MIBG、FDG或68Ga-DOTATATE亲和的骨病灶 3. 研究入组时双侧穿刺和活检至少一个样本中，基于常规形态学和/或免疫组织化学检测到的显微镜下骨髓转移。 * Lansky（<16岁）或Karnofsky（>16岁）量表体能状态>50%。因瘫痪而依赖轮椅的患者在评估体能评分时将被视为可走动。 * 研究入组四周内记录的基线心脏和肺功能充分，包括超声心动图左心室射血分数（LVEF）>50%以及室内空气下脉搏血氧饱和度>92%。 * 基线血液学功能充分：外周血绝对中性粒细胞计数（ANC）≥500/µL，研究入组前14天内未接受长效髓系生长因子或7天内未接受短效髓系生长因子，且血小板计数≥50,000/µL，患者需至少7天不依赖输血，除非血细胞减少与上述骨髓转移相关。 * 有可用的单倍体相合相关供者。 排除标准： * 感染性疾病：活动性、未控制的感染，或研究入组前30天内接种过活疫苗。 * 心脏功能：超声心动图LVEF <50%，严重未控制的心律失常，或心肌炎或充血性心力衰竭病史（纽约心脏协会功能分级III或IV级） * 肺功能：活动性间质性肺病（ILD）/肺炎，或需要全身性皮质类固醇治疗的ILD/肺炎病史。 * 肾功能：通过胱抑素C或NM GFR测定的肾小球滤过率（GFR）<50 mL/min/1.73 m2 * 肝功能：总胆红素>5 mg/dL，AST和ALT>正常上限的10倍 * 合并用药：每日接受泼尼松等效剂量>0.5 mg/kg * 在IP输注时30天内接受任何合并研究性治疗。这些研究性治疗包括仍在临床试验或研究环境中处于研究阶段的药物、生物制品或器械。使用此类药物可能会混淆研究结果或带来额外的安全风险 * 已知对IL-2注射剂过敏或超敏反应 * 妊娠或哺乳期妇女
Inclusion Criteria: * Age 1-39 years at the time of study enrollment * With diagnosis of neuroblastoma with histologic verification * Classified as high-risk neuroblastoma as defined by Children's Oncology Group (COG) risk classification, including patients initially classified as low or intermediate risk at diagnosis with subsequent reclassification as high-risk disease * With relapsed or refractory disease, including at least one of the following: 1. Recurrent disease at any time after completion of frontline therapy 2. Progressive disease at any time following standard induction therapy 3. Primary resistant or refractory disease defined by failure to achieve a complete response by International Neuroblastoma Response Criteria (INRC) after at least four cycles of standard, multidrug induction chemotherapy on or according to a high-risk neuroblastoma protocol * Patients must have evaluable disease documented within four weeks of study enrollment. Evaluable disease must include at least one of the following: 1. Measurable tumor (\>10 mm in at least one dimension) on MRI or CT scan that is either MIBG, FDG or 68Ga-DOTATATE avid 2. One or more MIBG, FDG, or 68Ga-DOTATATE avid bone lesion 3. Microscopic marrow metastasis based on routine morphology and/or immunohistochemistry in at least one sample from bilateral aspirates and biopsies at the time of study enrollment. * With performance level of \>50% on Lansky (\<16 years) or Karnofsky (\>16 years) scales. Patients who are wheelchair bound due to paralysis will be considered ambulatory when assessing their performance score. * Adequate baseline cardiac and pulmonary function including a left ventricular ejection fraction (LVEF) \>50% by echocardiogram and pulse oximetry \>92% on room air documented within four weeks of study enrollment. * Adequate baseline hematologic function: peripheral absolute neutrophil count (ANC) ≥500/µL, with no receipt of long-acting myeloid growth factors within 14 days or short-acting myeloid growth factors within 7 days of study entry, and a platelet count ≥50,000/µL, with patients required to be transfusion independent for at least 7 days, unless cytopenias are related to marrow metastasis as defined above. * With available haploidentical related donors. Exclusion Criteria: * Infectious disease: Active, uncontrolled infection or received a live vaccine within 30 days prior to study enrollment. * Cardiac function: LVEF \<50% by echocardiogram, serious uncontrolled cardiac arrhythmias, or history of myocarditis or congestive heart failure (New York Heart Association Functional Classification III or IV) * Pulmonary function: Active interstitial lung disease (ILD)/pneumonitis or history of ILD/pneumonitis requiring systemic corticosteroid treatment. * Renal function: Glomerular Function Rate (GFR) \<50 mL/min/1.73 m2 as measured by cystatin C or NM GFR * Hepatic function: Total bilirubin \>5 mg/dL, AST and ALT \>10 times the upper limit of normal * Concomitant medications: receiving \>0.5 mg/kg prednisone equivalent daily * Receipt of any concomitant investigational treatments within 30 days at the time of the infusion of the IP. These investigational treatments include drugs, biologics, or devices that are still under investigation in clinical trials or research settings. The use of such agents may confound study results or pose additional safety risks * Known allergy or hypersensitivity reaction to IL-2 injections * Pregnant or breastfeeding women
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：Infusional Toxicity · Number of subjects who receive an infusion of cytokine-induced memory-like natural killer cells (CIML-NK cells) without grade 3-4 infusional toxicity events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 divided by the number of patients enrolled. · 30 days
次要终点：Clinical Response or Disease Stability to Study Treatment
该研究性细胞产品是一种细胞因子诱导的记忆样自然杀伤细胞制剂，来源于受试者单倍体相合供者的单采产品。
本研究的目的是证明细胞因子诱导的记忆样自然杀伤细胞（CIML-NK细胞）可以从供体细胞中生成，并在基于dinutuximab的治疗期间安全地输注给复发或难治性神经母细胞瘤患者。
The goal of this study is to demonstrate that cytokine-induced memory-like natural killer cells (CIML-NK cells) can be generated from donor cells and infused safely into patients with relapsed or refractory neuroblastoma during dinutuximab-based therapy.
MEMBER ACCOUNT
登录成功会直接打开下一页。
