肿瘤细胞治疗研究
英文原题：Prophylactic TCRaB+ and CD19+ Depleted Donor Lymphocyte Infusion After Allogeneic Stem Cell Transplant in High-Risk Patients With Hematologic Malignancies
Prophylactic TCRaB+ and CD19+ Depleted Donor Lymphocyte Infusion After Allogeneic Stem Cell Transplant in High-Risk Patients With Hematologic Malignancies
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。
这是一项分期未标注的、非随机的注册临床试验，评估异体细胞治疗用于血液系统恶性肿瘤的疗效与安全性。研究设计：非随机、4 个分组。当前状态：招募中。计划入组 38 例。试验地点：美国 · 麦迪逊（共 1 个中心）。登记号：NCT07285668。
不限性别 · ≥ 18 Years 且 ≤ 80 Years
纳入标准： • 患有高危髓系或淋巴系恶性肿瘤并符合allo-SCT条件，包括以下疾病。可在确诊时或计划预处理前的任何时间判定：难治性AML或ALL；复发AML或ALL；按细胞遗传学和突变判定为欧洲白血病网（ELN）高危的AML；流式细胞术显示MRD阳性或移植前未达完全缓解（CR）的活动性疾病；初诊或移植前治疗期间原始细胞≥5%的MDS；按修订版国际预后评分系统（IPSS-R）或分子版IPSS（IPSS-M）判定的高危/极高危MDS；慢性期且至少3种治疗失败、加速期或急变期CML；按DIPSS-plus或MIPSS70+判定的高危原发性骨髓纤维化（PMF），或加速期/急变期PMF；移植时缓解不足部分缓解的复发/难治性恶性淋巴瘤或霍奇金病；最近治疗方案后无缓解或疾病稳定的高危慢性淋巴细胞白血病；以及主要研究者根据机构标准认为有临床移植必要的其他高危血液系统恶性肿瘤。 • allo-SCT供者须为亲属，HLA-A、B、C及DRB1位点经分子分型相合、不相合或半相合。 • ECOG评分0–2。 • 能理解并愿意签署书面知情同意书。 • 愿意遵守所有研究程序并在整个研究期间配合。 • 可能导致本人或伴侣妊娠的性关系参与者须从入组至研究治疗结束后4周采用可接受的避孕方法。 排除标准： • 移植前检查提示器官功能不佳：肌酐≥2.0 mg/dL；SGOT/SGPT≥ULN的5倍（是否进行肝活检由临床医生决定）；胆红素≥ULN的3倍（Gilbert综合征除外）；血红蛋白校正DLCO<50%；LVEF或短轴缩短率<40%。仅在主要研究者同意后方可对上述器官功能标准作例外处理，且须在受试者研究记录中明确记录。 • 未控制的并发疾病。 • 可能妨碍遵守研究要求的精神疾病或社会状况。
Inclusion Criteria: * Patients with high-risk myeloid or lymphoid malignancies determined to be eligible to undergo allo-SCT including but not limited to the conditions listed below. These criteria apply at the disease diagnosis or any time prior to the cyto-reductive therapy given before the planned conditioning: * Refractory acute myelogenous (AML) or lymphoid leukemia (ALL) * Relapsed AML or ALL * AML in European LeukemiaNet (ELN) high risk per cytogenetic and mutation * Any patients with minimal residual disease (MRD+) disease by flow cytometry or with active disease (not in complete remission (CR)) prior to allo-SCT * Myelodysplastic syndromes (MDS) with 5% or more blasts at initial diagnosis, or anytime during their treatment prior to allo-SCT. * Myelodysplastic syndrome (MDS) high risk or very high risk per Revised International Prognostic Scoring System (IPSS-R) or Molecular International Prognostic Scoring System (IPSS-M) * Chronic myelogenous leukemia (CML) in chronic phase failed 3 or more treatments, in accelerated or blast phase * High risk primary myelofibrosis (PMF) per Dynamic International Prognostic Scoring System (DIPSS)-plus or Mutation-enhanced International Prognostic Scoring System for Transplant-age Patients (MIPSS70+) * PMF in accelerated or blast phase * Recurrent or refractory malignant lymphoma or Hodgkin's disease with less than a partial response at transplant * High risk chronic lymphocytic leukemia defined as no response or stable disease to the most recent treatment regimen * Other high risk hematologic malignancies for which allo-SCT is deemed clinically necessary per PI and based on institutional standards * The donor for the allo-SCT must be: * Related AND * Matched OR mismatched OR haploidentical at HLA-A, -B, -C, and -DRB1 by molecular methods * ECOG performance score of 0-2 * Ability to understand and willingness to sign written informed consent document * Willing to comply with all study procedures and be available for the duration of the study * Individuals in sexual relationships that could result in pregnancy or impregnation of their partner must use an acceptable method of contraception§ from enrollment until 4 weeks after completing study treatment. Exclusion Criteria: • Poor organ function as follows (According to the pre-transplant workups results): * Creatinine ≥ 2.0 mg/dL * SGOT and SGPT ≥ 5 x ULN. Liver biopsy per clinician discretion. * Bilirubin ≥ 3 x ULN (unless Gilbert's syndrome) * DLCO \< 50% corrected for hemoglobin * Left ventricular ejection fraction or shortening fraction \< 40% NOTE: Exceptions to the above organ function exclusion criteria are allowable only with assent of the PI since the risks and benefits must be addressed for patients with potentially incurable hematologic malignancies. Such exceptions will be clearly documented in the subject's research record and will not be considered a deviation. * Patients with uncontrolled intercurrent illness * Patients with psychiatric illness/social situations that would limit compliance with study requirements
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 Adverse Events (AEs) from DLI to day 28 post-DLI · To assess safety of prophylactic TCRαβ+/CD19+ depleted donor lymphocyte infusion (αβT/B dep-DLI) after allogeneic stem cell transplant (allo-SCT) in high-risk patients with hematologic malignancies, incidence of AEs will be reported. · up to day 28 post-DLI (approximately day 63 on study)；Maximum Tolerated Dose or Maximum Administered Dose · MTD/MAD defined as the highest dose level at which less than 2 of 6 participants experience a DLT. · up to day 28 post-DLI (approximately day 63 on study)
次要终点：Incidence of grade II-IV acute Graft-versus-Host Disease (aGVHD) after αβT/B dep-DLI；Cumulative incidence of severe grade III-IV aGVHD after αβT/B dep-DLI；Chronic Graft-versus-Host Disease (GVHD) incidence after αβT/B dep-DLI；Efficacy assessed by 1 year Progression Free Survival (PFS)；Efficacy Assessed by Non-Relapse Mortality；Efficacy Assessed by Overall Survival；Efficacy Assessed by Incidence of Cytomegalovirus (CMV) Reactivation；Efficacy Assessed by Incidence of Fungal Infection
1×10⁶ CD3-CD56+细胞/kg。
2×10⁶ CD3-CD56+细胞/kg。
5×10⁶ CD3-CD56+细胞/kg。
0.5×10⁶ CD3-CD56+细胞/kg；仅在1级剂量无法耐受时使用。
以上邮箱 / 电话是登记库里的申办方联系方式，通常不直达某家医院。中国中心的联系方式请以医院或登记平台最新公示为准。
本研究旨在评估高危血液系统恶性肿瘤患者接受异基因干细胞移植（allo-SCT）后，预防性输注TCRαβ+/CD19+去除的供者淋巴细胞（αβT/B dep-DLI）的安全性并确定最大耐受剂量（MTD）。
This study is being done to assess the safety and determine the maximum tolerable dose (MTD) of TCRαβ+/CD19+-depleted Donor Lymphocyte Infusion (αβT/B dep-DLI) after allogeneic stem cell transplant (allo-SCT) in highrisk patients with hematologic malignancies.
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