Biomarker Verification in Pediatric Chronic Graft-Versus-Host Disease: Applied Biomarkers to Minimize Long Term Effects of Childhood/Adolescent Cancer Treatment (ABLE) / Pediatric Transplantation & Cellular Therapy Consortium (PTCTC)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 350
- 试验地点
- 16
- 主要终点
- Day 100 blood sample collection
研究概览
简要总结
This study will validate a previously developed pediatric prognostic biomarker algorithm aimed at improving prediction of risk for the later development of chronic graft-versus-host disease (cGvHD) in children and young adults undergoing allogeneic hematopoietic stem cell transplant.
By developing an early risk stratification of patients into low-, intermediate-, and high-risk for future cGvHD development (based upon their biomarker profile, before the onset of cGvHD), pre-emptive therapies aimed at preventing the onset of cGvHD can be developed based upon an individual's biological risk profile.
This study will also continue research into diagnostic biomarkers of cGvHD, and begin work into biomarker models that predict clinical response to cGvHD therapies.
详细描述
Chronic graft-versus-host disease (cGvHD) occurs when the new donor immune system "attacks" tissues in the recipient following allogeneic hematopoietic stem cell transplantation (HSCT), leading to chronic inflammation, scarring and fibrosis, impaired immunity (including immune deficiency and immune dysregulation), and altered organ system functioning. Almost any organ or system has the potential to be affected by cGvHD, although eight organ systems are classically involved, including the skin, eyes, mouth, lungs, liver, gastrointestinal tract, genitourinary tract, and the musculoskeletal system.
The investigators will be enrolling allogeneic HSCT recipients before conditioning, following these patients prospectively until 12-months (+/- 1 month) post-transplant for the development of all forms of GvHD (classical acute, late acute and chronic GvHD), collecting blood samples at day +60 (+/- 7 days), day +100 (+/- 14 days), and at the onset of either late acute or chronic GvHD. Two extra blood samples will be collected exclusively from HAPLO transplant recipients, who never developed any late-acute GvHD or chronic GVHD at the 6- and 12-month post-transplant time points. In addition, clinical data will be collected at different time points.
Case report forms of standard transplant related data will be completed and entered into a REDCap database.
Blood samples will be drawn and shipped to the Central Laboratory in Vancouver, BC, Canada, processed, analyzed, and the final biomarker risk algorithm completed. Selected clinicians will be offered to complete a short survey asking about their perception of the feasibility of altering their approach to cGvHD management based upon these results.
If chronic GvHD develops at any time after transplant (day 0 to 1 year), or if any form of GvHD occurs at or after day +100 (whether late acute, chronic GvHD, or overlap syndrome), a blood sample will be drawn before escalating immune suppression, and the onset GvHD case report form will be completed following the protocol. If chronic GvHD is confirmed, an additional CRF will be submitted at 24-months (+/- 3 months) post-transplant to document new chronic GvHD manifestations, severity, and response to therapy.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 0 Years 至 24 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
结局指标
主要结局
Day 100 blood sample collection
时间窗: Day 100 (+/- 14 days) post-transplant
Validation of prognostic and diagnostic power of cGvHD biomarkers and testing of the biomarker assay performance of Day 100 post-transplant blood sample (diagnostic biomarkers). Using this algorithm-based assay the investigators will attempt to develop risk assignment for cGvHD and L-aGvHD at Day 100. Flow Cytometry and ELISA assays will be used for biomarker measurement.
Clinical data collection at 24 months
时间窗: 24 Months (+/- 1 month) post-transplant
Case Report Form to be completed. Clinical data will be used in data analysis.
Day 60 blood sample collection
时间窗: Day 60 (+/- 7 days) post-transplant
Validation of prognostic and diagnostic power of cGvHD biomarkers and testing of the biomarker assay performance of Day 60 post-transplant blood sample. Using this algorithm-based assay the investigators will attempt to develop risk assignment for cGvHD and L-aGvHD at Day 60 and determine whether this time point has a similar (or improved) predictive value to the day +100 (+/-14 days). Flow Cytometry and ELISA assays will be used for biomarker measurement.
Onset CvHD blood sample collection
时间窗: The day of initial diagnosis
Validation of prognostic and diagnostic power of cGvHD biomarkers and testing of the biomarker assay performance of the GvHD onset blood sample. The investigators will attempt to determine whether biomarkers present at the onset of new late-acte GvHD developing after day +100 (diagnostic biomarkers) or are similar to or different than at the onset of chronic GvHD. Flow Cytometry and ELISA assays will be used for biomarker measurement.
Baseline transplant clinical data collection at Day 0
时间窗: Between day 0 (day of transplant) and day +21
Baseline Transplant Data Case Report Form to be completed. Clinical data will be used in data analysis.
Clinical data collection at Day 60
时间窗: Day 60 (+/- 7 days) post-transplant
Day 60 Case Report Form to be completed. Clinical data will be used in data analysis.
Clinical data collection at Day 100
时间窗: Day 100 (+/- 14 days) post-transplant
Case Report Form to be completed. Clinical data will be used in data analysis.
Clinical data collection at 6 months
时间窗: 6 Months (+/- 1 month) post-transplant
Case Report Form to be completed. Clinical data will be used in data analysis.
Clinical data collection at 12 months
时间窗: 12 Months (+/- 1 month) post-transplant
Case Report Form to be completed. Clinical data will be used in data analysis.
Clinical data collection at onset of GvHD
时间窗: At the time of diagnosis
Case Report Form to be completed. Clinical data will be used in data analysis.
次要结局
- Determination of patient's risk profile and prediction of treatment responses(At the end of the study by year 2025)
- Demonstration of identifiable and reproducible differences in diagnostics of cGvHD and L-aGvHD(At the end of the study by year 2025)
研究者
Kirk Schultz
Professor of Pediatrics
University of British Columbia