Biomarker Verification in Pediatric Chronic GvHD: ABLE 2.0 / PTCTC GVH 1901 Study
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|ClinicalTrials.gov Identifier: NCT04372524|
Recruitment Status : Recruiting
First Posted : May 4, 2020
Last Update Posted : June 22, 2022
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.
|Condition or disease|
|Chronic Graft-versus-Host-Disease Leukemia Allogeneic Hematopoietic Stem Cell Transplantation Blood Cancer Non-Malignant Hematologic and Lymphocytic Disorder|
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.
|Study Type :||Observational|
|Estimated Enrollment :||350 participants|
|Official Title:||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)|
|Actual Study Start Date :||November 15, 2020|
|Estimated Primary Completion Date :||January 2024|
|Estimated Study Completion Date :||January 2025|
Allogeneic HSC Transplant recipients
Five possible patient scenarios are anticipated to occur in those who underwent allogeneic HSCT:
- 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.
- 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.
- 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 24 months [ Time Frame: 24 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.
- Demonstration of identifiable and reproducible differences in diagnostics of cGvHD and L-aGvHD [ Time Frame: 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.
- Determination of patient's risk profile and prediction of treatment responses [ Time Frame: 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.
- 6 Month HAPLO blood sample collection [ Time Frame: 6 Months (+/- 1 month) post-transplant ]Blood sample from haploidentical transplant recipients who did not develop late-acute or chronic GvHD
- 12 Month HAPLO blood sample collection [ Time Frame: 12 Months (+/- 1 month) post-transplant ]Blood sample from haploidentical transplant recipients who did not develop late-acute or chronic
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04372524
|Contact: Elena Ostroumov, PhD||604-875-2000 ext 6648||Elena.Ostroumov@bcchr.ca|
|Contact: Sayeh Abdossamadi, PhDemail@example.com|
|United States, California|
|University of California San Francisco||Recruiting|
|San Francisco, California, United States, 94158|
|Contact: Kevin Magruder 415-476-3834 Kevin.Magruder@ucsf.edu|
|Principal Investigator: Alexis Melton, MD|
|United States, Colorado|
|Children's Hospital Colorado||Not yet recruiting|
|Denver, Colorado, United States, 80045|
|Contact: Kayla Ortiz Kayla.Pacheco@childrenscolorado.org|
|Principal Investigator: Amy Keating, MD|
|United States, Georgia|
|Emory University School of Medicine||Not yet recruiting|
|Atlanta, Georgia, United States, 30322|
|Contact: Judson Russel Judson.Russell@choa.org|
|Principal Investigator: Muna Qayed, MD, MsCR|
|United States, Missouri|
|Washington University School of Medicine||Not yet recruiting|
|Saint Louis, Missouri, United States, 63110|
|Contact: Sheri Kersting, CCRP firstname.lastname@example.org|
|Principal Investigator: Shalini Shenoy, MO, MD|
|United States, New York|
|Roswell Park Comprehensive Care Center||Recruiting|
|Buffalo, New York, United States, 14263|
|Contact: Heather Cameron 716-845-1780 Heather.Cameron@RoswellPark.org|
|Principal Investigator: Nataliya Prokopenko Buxbaum, MD|
|Memorial Sloan Kettering Cancer Center||Recruiting|
|New York, New York, United States, 10174|
|Contact: Chima Elenwune ElenwunC@mskcc.org|
|Principal Investigator: Andrew C Harris, MD|
|United States, North Carolina|
|University of North Carolina||Not yet recruiting|
|Chapel Hill, North Carolina, United States, 27599|
|Contact: Juanita Cuffee email@example.com|
|Principal Investigator: Kimberly A Kasow, DO|
|Atrium Health Levine Cancer Institute||Not yet recruiting|
|Charlotte, North Carolina, United States, 28203|
|Contact: Katie Cline Katie.Cline@atriumhealth.org|
|Principal Investigator: Michael W Kent, MD|
|United States, Ohio|
|Nationwide Children's Hospital||Recruiting|
|Columbus, Ohio, United States, 43205-2664|
|Contact: Lori Jewell Lori.Jewell@nationwidechildrens.org|
|Principal Investigator: Rajinder Bajwa, MD|
|United States, Oregon|
|Oregon Health & Science University Knight Cancer Institute||Recruiting|
|Portland, Oregon, United States, 97239-3098|
|Contact: Kinjal Mistry firstname.lastname@example.org|
|Principal Investigator: Eneida R Nemecek, MD, MS, MBA|
|United States, Tennessee|
|Vanderbilt University Medical Center||Not yet recruiting|
|Nashville, Tennessee, United States, 37232-6311|
|Contact: Lillie Flynn email@example.com|
|Principal Investigator: Carrie L Kitko, MD|
|Alberta Children's Hospital||Recruiting|
|Calgary, Alberta, Canada, T3B 6A8|
|Contact: Debra Rich Debra.Rich@albertahealthservices.ca|
|Principal Investigator: Victor Lewis, MD|
|Canada, British Columbia|
|BC Children's Hospital||Recruiting|
|Vancouver, British Columbia, Canada, V6H 3N1|
|Contact: Alecia Lim Alecia.Lim@cw.bc.ca|
|Principal Investigator: Kirk R. Schultz, MD|
|Sub-Investigator: Jacob Rozmus, MD, PhD|
|Sub-Investigator: Amanda Li, MD, MSc|
|CancerCare Manitoba||Active, not recruiting|
|Winnipeg, Manitoba, Canada, R3E 0V9|
|Montréal, Quebec, Canada, H3T 1C5|
|Contact: David Godin firstname.lastname@example.org|
|Principal Investigator: Henrique Bittencourt, MD, PhD|
|McGill University Health Centre||Recruiting|
|Montréal, Quebec, Canada, H4A 3J1|
|Contact: Samira Mezziani Samira.Mezziani@MUHC.MCGILL.CA|
|Principal Investigator: David Mitchell, MD|
|Principal Investigator:||Kirk R Schultz, MD||University of British Columbia / BC Children's Hospital Research Institute|
|Principal Investigator:||Andrew C Harris, MD||Memorial Sloan Kettering Cancer Center / Pediatric Stem Cell Transplantation and Cellular Therapies|