Biomarker Verification in Pediatric Chronic GvHD: ABLE 2.0 / PTCTC GVH 1901 Study
- Conditions
- Chronic Graft-versus-Host-DiseaseAllogeneic Hematopoietic Stem Cell TransplantationLeukemiaBlood CancerNon-Malignant Hematologic and Lymphocytic Disorder
- Registration Number
- NCT04372524
- Lead Sponsor
- University of British Columbia
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 350
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Day 100 blood sample collection 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.
Day 60 blood sample collection 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 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.
Clinical data collection at 24 months 24 Months (+/- 1 month) post-transplant Case Report Form to be completed. Clinical data will be used in data analysis.
Clinical data collection at Day 60 Day 60 (+/- 7 days) post-transplant Day 60 Case Report Form to be completed. Clinical data will be used in data analysis.
Baseline transplant clinical data collection at Day 0 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 100 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 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 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 At the time of diagnosis Case Report Form to be completed. Clinical data will be used in data analysis.
- Secondary Outcome Measures
Name Time Method Determination of patient's risk profile and prediction of treatment responses At the end of the study by year 2025 Utilizing cGvHD specific biomarkers, clinicians will be able to predict patient's treatment responses and chose the more accurate and effective treatment options.
Demonstration of identifiable and reproducible differences in diagnostics of cGvHD and L-aGvHD At the end of the study by year 2025 Metrics to measure this outcome will employ the difference in biomarkers (in combination with clinical manifestation) that can be used to discriminate between cGvHD and L-aGvHD and aid clinicians in establishing a more accurate diagnosis. Laboratory procedure and statistical data analysis will be used to achieve this.
Trial Locations
- Locations (16)
BC Children's Hospital
🇨🇦Vancouver, British Columbia, Canada
McGill University Health Centre
🇨🇦Montréal, Quebec, Canada
CancerCare Manitoba
🇨🇦Winnipeg, Manitoba, Canada
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
Children's Hospital Colorado
🇺🇸Denver, Colorado, United States
Emory University School of Medicine
🇺🇸Atlanta, Georgia, United States
University of North Carolina
🇺🇸Chapel Hill, North Carolina, United States
Roswell Park Comprehensive Care Center
🇺🇸Buffalo, New York, United States
Atrium Health Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
CHU Sainte-Justine
🇨🇦Montréal, Quebec, Canada
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Alberta Children's Hospital
🇨🇦Calgary, Alberta, Canada
Oregon Health & Science University Knight Cancer Institute
🇺🇸Portland, Oregon, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States