肿瘤细胞治疗研究
英文原题：NKX101, Intravenous Allogeneic CAR NK Cells, in Adults With AML or MDS
⚠ 该试验的登记信息已有 21 个月未更新， 页面上显示的「进行中（不再招募）」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，评估细胞治疗用于急性髓系白血病、骨髓增生异常综合征的安全性、可行性及初步疗效。当前状态：进行中（不再招募）。计划入组 61 例。试验地点：美国 · 丹佛、杰克逊维尔、亚特兰大、芝加哥（共 8 个中心）。登记号：NCT04623944。
不限性别 · ≥ 18 Years
纳入标准： * 一般条件：ECOG体能状态评分≤2。 * 疾病相关条件： * AML患者：既往接受过治疗的复发/难治性AML，包括微小残留病（MRD）阳性；既往抗白血病治疗不超过3线。对于可靶向的FLT3或IDH1/2突变患者，须至少接受过1种相应靶向治疗，既往治疗线数可达4线。白细胞计数≤25×10^9/L。接受氟达拉滨/环磷酰胺（±地西他滨）淋巴细胞清除后给予NKX101的队列，疾病须局限于骨髓（外周血原始细胞≤5%，且无髓外病变）。在方案所列的氟达拉滨/环磷酰胺（±地西他滨）或氟达拉滨/阿糖胞苷淋巴清除队列中，可纳入具有特定高危基因突变的其他患者；须按当地检测方法依据ELN 2022评估，并在入组前与申办方讨论。上述特定队列还可纳入造血细胞移植（HCT）后复发的患者。 * MDS患者：中危、高危或极高危MDS；既往治疗后复发/难治；既往接受至少1线且不超过3线标准MDS治疗。接受氟达拉滨/环磷酰胺（±地西他滨）淋巴清除的队列，可纳入具有特定高危疾病的其他患者，须按当地检测方法评估高危基因突变。接受氟达拉滨/环磷酰胺（±地西他滨）淋巴清除并给予NKX101的队列，也可纳入HCT后复发患者。 * 器官功能充分。 * 血小板计数≥30,000/μL（允许输注血小板）。 * 其他：已签署知情同意书；同意采用有效屏障避孕措施。 排除标准： * 疾病相关：急性早幼粒细胞白血病伴t(15;17)(q22;q12)或PML-RARA异常，或由慢性粒单核细胞白血病（CMML）演变的AML；有白血病性脑膜炎证据或已知活动性CNS疾病；外周血白细胞≥20,000/μL，或有其他快速进展疾病，导致受试者无法完成至少1个治疗周期；在NKX101首次给药前方案规定的时间窗内使用任何抗AML/MDS化疗药或靶向小分子药物；既往治疗造成的非血液学毒性尚未恢复至≤1级；16周内接受过任何造血细胞移植。 * 存在方案禁止的其他合并症或合并用药。 * 妊娠或哺乳期女性。
Inclusion Criteria:
* General:
* ECOG performance status ≤2
* Disease related:
* For AML subjects:
* Previously treated relapsed/refractory AML, including subjects with MRD+ disease
* Received at most 3 lines of previous anti-leukemia therapy
* For subjects with targetable fms-like tyrosine kinase 3 (FLT3)-mutated or isocitrate dehydrogenase (IDH)1/2 mutated disease, subjects must have received at least 1 prior respective targeted therapy and may receive up to 4 lines of prior therapy
* White blood cell count of ≤25 × 10\^9/L
* For groups receiving NKX101 after lymphodepletion with fludarabine/cyclophosphamide +/- decitabine: Disease localized to the bone marrow, as evidenced by ≤ 5% peripheral blasts and no evidence of extramedullary disease
* For groups receiving NKX101 after lymphodepletion with fludarabine/ cyclophosphamide +/- decitabine, group receiving NKX101 after lymphodepletion with fludarabine/ara-C: Additional subjects with specifically high-risk genetic mutations may be enrolled. High risk genetic mutation per ELN 2022 should be evaluated as per local assay and discussed with the Sponsor prior to study entry
* For groups receiving NKX101 after lymphodepletion with fludarabine/cyclophosphamide +/- decitabine, group receiving NKX101 after lymphodepletion with fludarabine/ara-C: Additional subjects who have relapsed following HCT may be enrolled.
* For MDS subjects:
* Intermediate-, high-, or very high-risk MDS
* Previously treated relapsed/refractory MDS
* Received at least 1 and at most 3 lines of previous standard anti-MDS therapy
* For groups receiving NKX101 after lymphodepletion with fludarabine/ cyclophosphamide +/- decitabine: Additional subjects with specifically high-risk disease may be enrolled. High-risk genetic mutation should be evaluated as per local assay
* For group receiving lymphodepletion with fludarabine/cyclophosphamide +/- decitabine and NKX101: Additional subjects who have relapsed following HCT may be enrolled.
* Adequate Organ Function
* Platelet count ≥30,000/uL (platelet transfusions acceptable)
* Other:
* Signed informed consent
* Agree to use an effective barrier method of birth control
Exclusion Criteria:
* Disease related:
* Acute promyelocytic leukemia with t(15;17) (q22;q12); or abnormal promyelocytic leukemia/retinoic acid receptor alpha (APML-RARA) and AML arising from chronic myelomonocytic leukemia (CMML)
* Evidence of leukemic meningitis or known active central nervous system disease
* Peripheral leukocytosis with ≥ 20,000 blasts/μL or other evidence of rapidly progressive disease that would preclude subject from completing at least 1 cycle of treatment
* Use of any anti-AML/MDS chemotherapeutic or targeted small molecule drug within protocol specified window prior to the first dose of NKX101
* Presence of residual non-hematologic toxicity from prior therapies that has not resolved to ≤ Grade 1
* Any hematopoietic cell transplantation within 16 weeks
* Other comorbid conditions and concomitant medications prohibited as per study protocol
* Other:
* Pregnant or lactating female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：Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] · Incidence, nature, and severity of treatment related adverse events will be evaluated. An adverse event is any unfavorable and unintended sign including clinically significant abnormal laboratory findings, symptom or disease. · 30 days after last dose of NKX101；Response rate to NKX101 (for Part 2) · Responses will be assessed per modified ELN criteria and will include complete and partial remission with and without varying degrees of hematologic recovery · 28 days from first dose of NKX101
次要终点：Assessment of NKX101 half-life；NKX101 duration of persistence；Evaluation of host immune response against NKX101；Response rate to NKX101
第1部分所有受试者均接受氟达拉滨/环磷酰胺淋巴细胞清除，随后每周给予NKX101，共3剂或2剂（分别对应方案A或B）。第2部分受试者接受氟达拉滨/环磷酰胺或氟达拉滨/阿糖胞苷（Ara-C）淋巴细胞清除；如开放可选组，则接受氟达拉滨/环磷酰胺联合地西他滨淋巴细胞清除，随后每周给予NKX101，共3剂。第2部分使用无关供者来源的现货型NKX101。
这是一项单臂、开放标签、多中心Ⅰ期研究，旨在评估试验性疗法NKX101（靶向NKG2D配体的异基因CAR-NK细胞）用于复发/难治性急性髓系白血病（AML）或中、高、极高危复发/难治性骨髓增生异常综合征（MDS）患者的安全性和耐受性。
This is a single-arm, open-label, multi-center, Phase 1 study to determine safety and tolerability of an experimental therapy called NKX101 (allogeneic CAR NK cells targeting NKG2D ligands) in patients with relapsed/refractory AML or intermediate, high and very high risk relapsed/refractory MDS.
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