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)
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Chronic Graft-versus-Host-Disease
- Sponsor
- University of British Columbia
- Enrollment
- 350
- Locations
- 16
- Primary Endpoint
- Day 100 blood sample collection
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
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.
Detailed Description
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. Study participants will have between 2 and 4 blood samples drawn over the course of 1-year post-transplant, depending upon their event and GvHD status.
Investigators
Kirk Schultz
Professor of Pediatrics
University of British Columbia
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
Day 100 blood sample collection
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: At the time of diagnosis
Case Report Form to be completed. Clinical data will be used in data analysis.
Secondary Outcomes
- 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)