Biomarkers of Endothelial Dysfunction in Pediatric Patients Receiving High Intensity Chemotherapy/Irradiation
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 80
- 试验地点
- 4
- 主要终点
- SOS proteomic markers
研究概览
简要总结
The goal of this is to learn more about stem cell transplant and complications that some people have after their transplants, in particular sinusoidal obstruction syndrome (SOS), also called veno-occlusive disease of the liver.
详细描述
This is a multicenter, prospective, observational trial. We will measure biomarkers and determine thresholds that will predict increased risk for SOS in pediatric patients receiving HCT or high intensity chemotherapy/irradiation with the future goal of a randomized, interventional, open-label, multicenter trial that will test the preemptive use of defibrotide for prevention of SOS in an enriched high-risk population.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- — 至 25 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≤ 25 years undergoing HCT for any reason who fulfill any ONE (1) of the following criteria:
- •History of hepatic disease as defined by:
- •Viral hepatitis (i.e., hepatitis C virus [HCV])
- •Liver tumor before HCT
- •Hepatic fibrosis or cirrhosis before HCT as proven by liver biopsy
- •High aspartate aminotransferase (AST) (> 2x ULN) before HCT (pre-transplant evaluation)
- •High alanine transaminase (ALT) (> 2x ULN) before HCT
- •High bilirubin (> 1.2x ULN) before HCT
- •HCT high-risk features including:
- •a. Conditioning with high-risk modalities including: i. Busulfan (BU)-containing regimen particularly with oral BU + cyclophosphamide ii. TBI-containing regimen, particularly cyclophosphamide + total-body irradiation (TBI) b. ≥ 2 HCT c. Allo-HCT for leukemia > or = second relapse d. Unrelated donor (URD) HCT e. Human leukocyte antigen (HLA) mismatch HCT (less than 10 of 10 for bone marrow/peripheral blood stem cell [BM/PBSC] or anything less than 6 of 6 for UCB) f. Use of sirolimus + tacrolimus prophylaxis for GVHD
- •High-risk disease states including:
- •Juvenile myelo-monocytic chronic leukemia (JMML)
- •Primary hemophagocytic lymphohistiocytosis (HLH)
- •Adrenoleukodystrophy
- •Osteopetrosis
- •Other high-risk features including:
- •Prior treatment with gemtuzumab ozogamicin
- •Use of hepatotoxic drugs 1 month before HCT and during HCT
- •Iron overload (i.e., thalassemia/sickle cell) with serum ferritin > 1000ng/ml
- •Deficit of ATIII, T-PA (i.e., < 30% normal values), and resistance to activated protein C if clinical indication (these values do not have to be specifically checked if no clinical history)
- •Young age < 2 years but more than 1 month
排除标准
- •Patients who are transplanted but do not fulfill any of the above mentioned criteria.
结局指标
主要结局
SOS proteomic markers
时间窗: Until the end of the study evaluation, day 180
Measure for 3 SOS proteomic markers, L-Ficolin, HA, and ST2, as early predictors of SOS incidence through study completion.
次要结局
未报告次要终点
研究者
Sophie Paczesny
Professor, Department of Pediatrics
Indiana University