A Phase II Study of Cytokine Induced Memory-like (CIML) Natural Killer (NK) Cell Adoptive Therapy after Haploidentical Donor Hematopoietic Cell Transplantation.
单倍相合供体造血细胞移植后细胞因子诱导记忆样 (CIML) 自然杀伤 (NK) 细胞过继治疗的 II 期研究。
基本信息
- 批准号:10165782
- 负责人:
- 金额:$ 16.96万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-07-27 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:Acute Myelocytic LeukemiaAdoptive Cell TransfersAdultAgeAllogenicBone Marrow TransplantationCell TherapyCellular immunotherapyClinicalClinical TrialsClinical Trials NetworkCorrelative StudyCyclophosphamideDiseaseDoseElderlyEnvironmentEvaluable DiseaseExhibitsGoalsHaptensHematocrit procedureHematopoietic NeoplasmsHematopoietic Stem Cell TransplantationHomologous TransplantationIL18 geneImmuneImmunologyImmunotherapyIn VitroIncidenceInstitutionInterleukin-12Interleukin-15LongevityMediatingMemoryMulticenter TrialsMusNatural Killer CellsOutcomePatientsPhasePhase II Clinical TrialsPopulationPrognosisPropertyProphylactic treatmentRefractoryRelapseReportingSafetyStem cell transplantTimeToxic effectTransplantationUnited StatesUniversitiesVertebral columnVirus DiseasesWashingtonXenograft Modelacute myeloid leukemia cellclinical centerconditioningcytokinedonor stem celleffective therapyexperimental studyfirst-in-humangraft vs host diseasegraft vs leukemia effecthematopoietic cell transplantationhigh riskhigh risk populationhuman studyin vivoleukemiamortalitymouse modelnovelolder patientphase 2 studyphase II trialpost-transplantpreservationprogramsrelapse riskresponsetreatment comparisontrial design
项目摘要
Abstract
The Bone Marrow Transplant (BMT)/Leukemia Program at Washington University ranks among the
largest in the United States, performing over 400 transplants annually, including over 200 allogeneic
transplants. The program has been affiliated with the BMT Clinical Trials Network (CTN) since its inception,
initially as part of the Case Western Consortium, and more recently as a Core Center since 2011. During this
time, our institution has made significant contributions to CTN through clinical trials accrual and trial design
input. As part of this application for renewal as a Core Clinical Center, we propose a phase II clinical trial
incorporating the use of a novel cellular therapy into a haploidentical transplant platform for elderly patients
with relapsed refractory AML. The basis for this proposal is the demonstration that NK cells stimulated ex vivo
with a cocktail of cytokines (IL12, IL15, IL18), exhibit an enhanced memory–like response to subsequent AML
cell exposure both in vitro and in vivo in a mouse xenograft model. These observations led to a phase I dose-
finding clinical trial to establish safety of haploidentical cytokine-induced memory-like (CIML) NK cells as
therapy for elderly adults with relapsed AML, which has been concluded, and an ongoing phase II trial to define
efficacy, with favorable preliminary results. On this basis, we propose to incorporate this CIML NK cell
approach into a backbone of haploidentical donor stem cell transplantation with reduced intensity conditioning
and post-transplant cyclophosphamide for elderly adults with relapsed AML. Our hypothesis is that this
strategy will lower the incidence of relapse in this high risk population while preserving the tolerability of the
reduced intensity conditioning approach. Completion of this study would require accrual of 30 patients,
anticipated over a 2-year period in the context of a multi-center trial.
抽象的
华盛顿大学的骨髓移植 (BMT)/白血病项目名列前茅
美国最大的移植中心,每年进行 400 多例移植手术,其中包括 200 多例同种异体移植
该计划自成立以来一直隶属于 BMT 临床试验网络 (CTN),
最初是 Case Western 联盟的一部分,最近自 2011 年起成为核心中心。
当时,我们机构通过临床试验应计和试验设计为CTN做出了重大贡献
作为核心临床中心更新申请的一部分,我们建议进行 II 期临床试验。
将新型细胞疗法的使用纳入老年患者的半相合移植平台中
该提案的基础是证明 NK 细胞可以进行离体刺激。
与细胞因子混合物(IL12、IL15、IL18)结合,对随后的 AML 表现出增强的记忆样反应
在小鼠异种移植模型中体外和体内的细胞暴露这些观察导致了第一阶段剂量-。
寻找临床试验来确定半相合细胞因子诱导的记忆样 (CIML) NK 细胞的安全性
针对患有复发性 AML 的老年人的治疗已结束,并且正在进行一项 II 期试验来定义
在此基础上,我们建议将这种 CIML NK 细胞纳入其中。
降低强度调节的半相合供体干细胞移植的骨干方法
和移植后环磷酰胺治疗患有复发性 AML 的老年人。
该策略将降低这一高危人群的复发率,同时保持对药物的耐受性
完成这项研究需要招募 30 名患者,
预计在多中心试验的背景下将持续两年的时间。
项目成果
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PETER WESTERVELT其他文献
PETER WESTERVELT的其他文献
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{{ truncateString('PETER WESTERVELT', 18)}}的其他基金
A Phase II Study of Cytokine Induced Memory-like (CIML) Natural Killer (NK) Cell Adoptive Therapy after Haploidentical Donor Hematopoietic Cell Transplantation.
单倍相合供体造血细胞移植后细胞因子诱导记忆样 (CIML) 自然杀伤 (NK) 细胞过继治疗的 II 期研究。
- 批准号:
10430084 - 财政年份:2017
- 资助金额:
$ 16.96万 - 项目类别:
A Phase II Study of Cytokine Induced Memory-like (CIML) Natural Killer (NK) Cell Adoptive Therapy after Haploidentical Donor Hematopoietic Cell Transplantation.
单倍相合供体造血细胞移植后细胞因子诱导记忆样 (CIML) 自然杀伤 (NK) 细胞过继治疗的 II 期研究。
- 批准号:
9385676 - 财政年份:2017
- 资助金额:
$ 16.96万 - 项目类别:
A Phase II Study of Cytokine Induced Memory-like (CIML) Natural Killer (NK) Cell Adoptive Therapy after Haploidentical Donor Hematopoietic Cell Transplantation.
单倍相合供体造血细胞移植后细胞因子诱导记忆样 (CIML) 自然杀伤 (NK) 细胞过继治疗的 II 期研究。
- 批准号:
9535449 - 财政年份:2017
- 资助金额:
$ 16.96万 - 项目类别:
Sargrastim and Plerixafor vs. Filgrastim for Allogeneic Stem Cell Mobilization
沙格司亭和普乐沙福对比非格司亭用于同种异体干细胞动员
- 批准号:
8316237 - 财政年份:2011
- 资助金额:
$ 16.96万 - 项目类别:
Sargrastim and Plerixafor vs. Filgrastim for Allogeneic Stem Cell Mobilization
沙格司亭和普乐沙福对比非格司亭用于同种异体干细胞动员
- 批准号:
8495404 - 财政年份:2011
- 资助金额:
$ 16.96万 - 项目类别:
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A Phase II Study of Cytokine Induced Memory-like (CIML) Natural Killer (NK) Cell Adoptive Therapy after Haploidentical Donor Hematopoietic Cell Transplantation.
单倍相合供体造血细胞移植后细胞因子诱导记忆样 (CIML) 自然杀伤 (NK) 细胞过继治疗的 II 期研究。
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$ 16.96万 - 项目类别:
A Phase II Study of Cytokine Induced Memory-like (CIML) Natural Killer (NK) Cell Adoptive Therapy after Haploidentical Donor Hematopoietic Cell Transplantation.
单倍相合供体造血细胞移植后细胞因子诱导记忆样 (CIML) 自然杀伤 (NK) 细胞过继治疗的 II 期研究。
- 批准号:
10430084 - 财政年份:2017
- 资助金额:
$ 16.96万 - 项目类别:
A Phase II Study of Cytokine Induced Memory-like (CIML) Natural Killer (NK) Cell Adoptive Therapy after Haploidentical Donor Hematopoietic Cell Transplantation.
单倍相合供体造血细胞移植后细胞因子诱导记忆样 (CIML) 自然杀伤 (NK) 细胞过继治疗的 II 期研究。
- 批准号:
9535449 - 财政年份:2017
- 资助金额:
$ 16.96万 - 项目类别: