肿瘤细胞治疗研究
英文原题：Donor-Derived Ex-Vivo Expanded Natural Killer Cell Infusions in Children and Young Adults With High Risk Acute Myeloid Leukemia Receiving Myeloablative HLA-Haploidentical Hematopoietic Cell Transplant
Donor-Derived Ex-Vivo Expanded Natural Killer Cell Infusions in Children and Young Adults With High Risk Acute Myeloid Leukemia Receiving Myeloablative HLA-Haploidentical Hematopoietic Cell Transplant
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
⚠ 该试验的登记信息已有 17 个月未更新， 页面上显示的「邀请入组」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 II 期注册临床试验，评估供者来源 NK 细胞治疗急性髓系白血病的安全性、可行性及初步疗效。当前状态：邀请入组。计划入组 30 例。试验地点：美国 · 凤凰城、洛杉矶、奥罗拉、奥兰多（共 13 个中心）。登记号：NCT04836390。
不限性别 · ≥ 0 Years 且 ≤ 25 Years
纳入标准： * 入组时年龄≤25岁； * 符合以下任一高危AML定义： * AML首次完全缓解（CR1；骨髓形态学和流式细胞术检测原始细胞<5%），且至少具有以下一项高危特征：与高危疾病相关的突变（见附录A）；附录A未明确列出的其他高危特征，经与方案主席/团队讨论并批准后也可考虑；或诱导化疗Ⅰ结束时微小残留病（MRD）阳性（流式细胞术原始细胞≥0.1%）； * AML达到第二次或以后完全缓解（≥CR2；骨髓形态学和流式细胞术原始细胞<5%）； * 从上一疗程化疗中恢复，定义为中性粒细胞绝对计数≥500/mm³； * 继发于特定生殖系骨髓衰竭疾病的AML可能符合条件（范可尼贫血除外），但入组前须获方案主席批准； * 体能状态≥70%（<16岁用Lansky评分，≥16岁用Karnofsky评分）； * 主要器官系统功能充分： * 肾脏：按Cockcroft-Gault公式、Schwartz公式或核医学GFR检查测得肌酐清除率（CrCl）≥60 mL/min/1.73 m²（见表3）； * 肝脏：总胆红素<2 mg/dL（Gilbert综合征所致者除外），ALT和AST<正常值上限（ULN）的5倍； * 心脏：静息左心室射血分数≥50%或短轴缩短率≥27%（MUGA或超声心动图）； * 肺部：血红蛋白校正后的DLCO、FEV1和FVC均≥预计值的50%；<7岁或不能完成肺功能检查者，室内空气脉搏血氧饱和度>92%，且静息时不吸氧； * 患者、患者父母、监护人或法定代理人能够提供书面知情同意。 排除标准： * 存在活动性髓外疾病； * 经适当治疗后病毒、细菌或真菌感染仍未缓解/持续存在且病情严重； * 有生育能力女性妊娠试验阳性； * 无法遵守药物治疗或随访要求； * 既往接受过异体移植； * 患有范可尼贫血或唐氏综合征。
Inclusion Criteria: * Age ≤ 25 years at time of enrollment * High-risk AML, as defined by one of the following: * AML in CR1 (defined as \<5% blasts in BM by morphology and flow cytometry) having at least one of these high-risk features: * Mutations associated with high risk disease (Appendix A). Other high-risk features not explicitly stated in Appendix A can be considered after discussion/approval with the protocol chair/team * MRD-positive at the end of Induction I chemotherapy (defined as flow cytometry ≥ 0.1% blasts) * AML in ≥CR2 (defined by \<5% blasts in BM by morphology and flow cytometry) * Recovery from prior cycle of chemotherapy as defined by an absolute neutrophil count ≥ 500/mm3 * AML secondary to select germline marrow failure disorders (with exception of Fanconi Anemia) may be eligible but require approval from Protocol Chairs prior to enrollment. * Performance status ≥70% (Lansky for \<16 years; Karnofsky for ≥16 years) * Adequate major organ system function as demonstrated by: * Renal: Creatinine clearance (CrCl) ≥60 mL/min/1.73m2 by Cockcroft-Gault formula, Schwartz formula, or nuclear GFR study (Table 3) * Hepatic: Total bilirubin \<2 mg/dL (unless due to Gilbert syndrome) and ALT and AST \< 5x ULN * Cardiac: LVEF at rest ≥50% or SF ≥27% (by MUGA or ECHO) * Pulmonary: DLCO, FEV1, and FVC ≥ 50% of predicted corrected for hemoglobin. For patients \<7 years of age or those unable to perform PFTs: O2 Sat \>92% on room air by pulse oximetry and on no supplemental O2 at rest * The patient, patient's parent, guardian, or legal representative can provide written informed consent Exclusion Criteria: * Active extramedullary disease * Unresolved/ongoing and serious viral, bacterial, or fungal infection despite appropriate treatment * Positive pregnancy test in a female of child-bearing potential (FCBP) * Inability to comply with medical therapy or follow-up * Prior allogeneic transplant * Patients with Fanconi Anemia and Down syndrome
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：1-year RFS · The proportion and corresponding 95% exact binomial CI of patients who are relapse-free at 1-year from day of transplant (Day 0) · 1 year
次要终点：Number of functional donor-derived NK cells generated from the device；GVHD incidence；KIR ligand-ligand mismatch；Incidence of mixed donor chimerism；Cumulative incidence of neutrophil engraftment；Cumulative incidence of platelet engraftment
所有受试者均接受NK细胞输注。
这是一项Ⅱ期探索性研究，旨在确定对接受清髓性HLA半相合造血细胞移植的高危急性髓系白血病（AML）儿童和青年，输注3次固定剂量（每次1×10⁸/kg）体外扩增的人类白细胞抗原（HLA）半相合供者自然杀伤（NK）细胞（haploNK）的疗效。受试者接受以白消安和环磷酰胺为基础的清髓性预处理方案，并在移植后接受环磷酰胺预防移植物抗宿主病（GVHD）。研究者还将评估在多中心开展该试验的可行性。 研究假设，在这一治疗背景下输注haploNK可促进免疫重建，减少复发和感染并发症，且不会增加GVHD；与近期未输注NK细胞的半相合造血细胞移植历史队列相比，可改善患者生存。
This is a Phase II pilot study to determine the efficacy of three fixed dose (1 x 108/kg) infusions of ex-vivo expanded human leukocyte antigen (HLA)-haploidentical donor natural killer (NK) cells (haploNK) in children and young adults with high risk acute myeloid leukemia (AML) undergoing HLA-haploidentical hematopoietic cell transplant (haploHCT) with a busulfan and cyclophosphamide-based myeloablative conditioning regimen and post-transplant cyclophosphamide (PTCy) for graft versus host disease (GVHD) prophylaxis. The investigators will also demonstrate the feasibility of performing this trial in a multi-center study. The investigators hypothesize that the infusion of haploNK in this setting will facilitate immune reconstitution and decrease relapse rates and infectious complications without increasing GVHD, resulting in improved survival as compared to recent historical cohorts of haploHCT without NK cell infusion.
MEMBER ACCOUNT
登录成功会直接打开下一页。
