GVHD Clinical Trials and Biomarkers
GVHD 临床试验和生物标志物
基本信息
- 批准号:8331340
- 负责人:
- 金额:$ 18.38万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-09-09 至 2015-08-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAllogeneic Bone Marrow TransplantationAllogenicAntigen-Presenting CellsAreaBiologicalBiological MarkersBloodBone Marrow TransplantationCell physiologyClinical ProtocolsClinical ResearchClinical TrialsClinical Trials DesignComorbidityComplicationDataDevelopmentDiagnosisDiagnosticDiseaseDisease PathwayDoseFunctional disorderGoalsGrowthHematopoietic Stem Cell TransplantationHistone Deacetylase InhibitorHydroxamic AcidsImmunosuppressionInstructionLaboratoriesMalignant - descriptorMalignant NeoplasmsMarrowModalityMolecularOrganPatientsPharmaceutical PreparationsPhase II Clinical TrialsPlasmaPopulationPrevention strategyProcessProphylactic treatmentProteinsProteomeProteomicsPublishingRegimenResearchResistanceRiskSamplingSensitivity and SpecificitySkinSteroidsSymptomsT-LymphocyteTechnologyTestingTherapeuticTranslatingTransplantationUrsidae FamilyVorinostatWorkbaseconditioningdisease diagnosisdisorder preventiongraft vs host diseasehigh riskmortalitynovelolder patientoutcome forecastpatient populationpreventprognosticstandard caretherapeutic targettranslational clinical trial
项目摘要
PROJECT SUMMARY (See instructions):
New treatments are needed for graft-vs-host disease (GVHD), the most serious complication of allogeneic
bone marrow transplantation (BMT). Current pharmacologic agents for GVHD prevention and treatment
primarily target one of the essential effectors for GVHD, donor T cells. Other key effectors for GVHD, and
therefore potential therapeutic targets, are antigen presenting cells (APCs). Extensive experimental data
developed by this PPG support the conduct of translational clinical trials to test agents that act upon this
additional GVHD mechanism. We have demonstrated that APC function can be modulated by histone
deacetylase inhibitors (HDACi) and in preliminary data we published, that the HDACi, suberoylanalide
hydroxamic acid (SAHA), also known as vorinostat, regulates experimental GVHD. In this project will
perform a unique clinical trial of this drug for GVHD prevention. A further advance in GVHD, the
individualization of treatment, is presently hampered because GVHD can not be predicted precisely, the
diagnosis is often hard to establish, and patients whose GVHD is likely to be resistant to standard therapy
can not be identified. One of the first GVHD biomarker panels with predictive and diagnostic power was
identified in work supported by this projecL We have recently identified multiple additional biomarkers
using a large-scale proteomics discovery approach. In this project we will integrate newly discovered
biomarkers with those already validated to create informative and clinically useful panels for allogeneic
BMT patients. The Specific Aims are:
1. To conduct a Phase II trial using the HDACi, vorinostat in addition to standard immunosuppression to
prevent GVHD in related donor reduced intensity transplantation
2. To develop biomarkers specific to GVHD target organs (skin and Gl tract).
3. To validate eight newly discovered candidate proteins as biomarkers for the diagnosis, prognosis and
prediction of systemic acute GVHD.
4. To optimize predictive, diagnostic, and prognostic biomarker panels using validated combinations of
target organ specific and systemic biomarkers and to analyze their value in new clinical trials.
项目总结(见说明):
移植物抗宿主病(GVHD)是同种异体移植最严重的并发症,需要新的治疗方法。
骨髓移植(BMT)。目前用于GVHD预防和治疗的药物
主要靶向GVHD的重要效应物之一,供体T细胞。GVHD的其他关键效应物,以及
因此潜在的治疗靶点是抗原呈递细胞(APC)。大量的实验数据
该PPG开发的药物支持进行转化临床试验,以测试作用于此的药物
GVHD机制。我们已经证明,APC功能可以通过组蛋白调节,
在我们发表的初步数据中,HDACi,辛二酰苯胺
异羟肟酸(SAHA),也称为伏立诺他,调节实验性GVHD。在这个项目中,
对这种药物进行独特的临床试验,以预防GVHD。GVHD的进一步进展,
个体化治疗目前受到阻碍,因为GVHD不能精确预测,
诊断通常很难确定,GVHD患者可能对标准治疗有抵抗力,
无法识别。具有预测和诊断能力的首批GVHD生物标志物组之一是
在该项目支持的工作中发现了L我们最近发现了多种额外的生物标志物
使用大规模蛋白质组学发现方法。在这个项目中,我们将整合新发现的
生物标志物与那些已经验证的生物标志物,以创建信息丰富和临床有用的面板,用于同种异体
骨髓移植患者。具体目标是:
1.为了进行一项使用HDACi、伏立诺他以及标准免疫抑制剂的II期试验,
在相关供体降低强度移植中预防GVHD
2.开发GVHD靶器官(皮肤和胃肠道)特异性生物标志物。
3.为了验证八种新发现的候选蛋白作为诊断,预后和治疗的生物标志物,
预测系统性急性GVHD。
4.使用经验证的以下组合优化预测、诊断和预后生物标志物组:
靶器官特异性和全身性生物标志物,并分析其在新的临床试验中的价值。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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JOHN LEVINE其他文献
JOHN LEVINE的其他文献
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{{ truncateString('JOHN LEVINE', 18)}}的其他基金
Mount Sinai Core Clinical Consortium for the BMT Clinical Trials Network
BMT 临床试验网络西奈山核心临床联盟
- 批准号:
10429967 - 财政年份:2017
- 资助金额:
$ 18.38万 - 项目类别:
Mount Sinai Core Clinical Consortium for the BMT Clinical Trials Network
BMT 临床试验网络西奈山核心临床联盟
- 批准号:
9384886 - 财政年份:2017
- 资助金额:
$ 18.38万 - 项目类别:
Mount Sinai Core Clinical Consortium for the BMT Clinical Trials Network
BMT 临床试验网络西奈山核心临床联盟
- 批准号:
10160945 - 财政年份:2017
- 资助金额:
$ 18.38万 - 项目类别:
Mount Sinai Core Clinical Consortium for the BMT Clinical Trials Network
BMT 临床试验网络西奈山核心临床联盟
- 批准号:
10657592 - 财政年份:2017
- 资助金额:
$ 18.38万 - 项目类别:
Phase II Study of a Novel GVHD Prevention Strategy: Etanercept and Photopheresis
新型 GVHD 预防策略的 II 期研究:依那西普和光采术
- 批准号:
8425067 - 财政年份:2011
- 资助金额:
$ 18.38万 - 项目类别:
Phase II Study of a Novel GVHD Prevention Strategy: Etanercept and Photopheresis
新型 GVHD 预防策略的 II 期研究:依那西普和光采术
- 批准号:
8213524 - 财政年份:2011
- 资助金额:
$ 18.38万 - 项目类别:
Phase II Study of a Novel GVHD Prevention Strategy: Etanercept and Photopheresis
新型 GVHD 预防策略的 II 期研究:依那西普和光采术
- 批准号:
8029313 - 财政年份:2011
- 资助金额:
$ 18.38万 - 项目类别:
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