Chronic Graft-versus-Host-DiseaseNCT04372524
Biomarker Verification in Pediatric Chronic GvHD: ABLE 2.0 / PTCTC GVH 1901 Study
An observational study of Chronic Graft-versus-Host-Disease and Leukemia, run by University of British Columbia at 16 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 0 to 24 years
- Conditions the study is for
- Chronic Graft-versus-Host-Disease, Leukemia, Allogeneic Hematopoietic Stem Cell Transplantation
- How many people
- 350 participants
- Where
- 16 sitesin 2 countries
- Study dates
- 15 Nov 2020to Jan 2025
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 to 24 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Pediatric and adult (under age of 25 y.o.) patients undergoing allogeneic HSCT (hematopoietic stem cell transplantation) before the start of the conditioning regimen.
Who may be able to join
- Any indication for allogeneic hematopoietic stem cell transplant (malignant or non-malignant)
- Age 0 - 24.99 years at the time of transplant (on day 0)
- Any conditioning regimen (including myeloablative or reduced-toxicity/reduced-intensity)
- Any graft source (bone marrow, peripheral blood, cord blood)
- Any graft-versus-host disease prophylaxis strategy, including serotherapy such as ATG or alemtuzumab
- Haploidentical transplants, including post-transplant cyclophosphamide and alpha-beta TCR depletion, are allowed
Who cannot join
- Second or greater allogeneic transplant
- Weight 7 kg or less
- Pure CD34+ selected haploidentical stem cell transplant (not including CD34 enrichment used in alpha-beta TCR depleted haploidentical transplants, which is allowed)
- Inability of a center to follow a patient for the development of late-acute and chronic GVHD until 1-year post-transplant (referral sites who transplant patients from outside institutions should not enroll participants if sending back to the referring site early, such that long-term follow up, blood, and data collection cannot be assured).
Trial locations and contacts
16 sites in 2 countries.
16 sites in 2 countries
United States11 sites, 11 recruiting
- Not yet recruiting
Emory University School of Medicine
Atlanta, Georgia, 30322
Judson Russel, Judson.Russell@choa.org
Muna Qayed, MD, MsCR
- Recruiting
Roswell Park Comprehensive Care Center
Buffalo, New York, 14263
Heather Cameron, 716-845-1780, Heather.Cameron@RoswellPark.org
Nataliya Prokopenko Buxbaum, MD
- Not yet recruiting
University of North Carolina
Chapel Hill, North Carolina, 27599
Juanita Cuffee, juanita_cuffee@med.unc.edu
Kimberly A Kasow, DO
- Recruiting
Atrium Health Levine Cancer Institute
Charlotte, North Carolina, 28203
Katie Cline, Katie.Cline@atriumhealth.org
Michael W Kent, MD
- Recruiting
Nationwide Children's Hospital
Columbus, Ohio, 43205-2664
Lori Jewell, Lori.Jewell@nationwidechildrens.org
Rajinder Bajwa, MD
- Recruiting
Children's Hospital Colorado
Denver, Colorado, 80045
Kayla Ortiz, Kayla.Pacheco@childrenscolorado.org
Amy Keating, MD
- Recruiting
Vanderbilt University Medical Center
Nashville, Tennessee, 37232-6311
Lillie Flynn, lillian.f.flynn@vumc.org
Carrie L Kitko, MD
- Recruiting
Memorial Sloan Kettering Cancer Center
New York, New York, 10174
Chima Elenwune, ElenwunC@mskcc.org
Andrew C Harris, MD
- Recruiting
Oregon Health & Science University Knight Cancer Institute
Portland, Oregon, 97239-3098
Kinjal Mistry, mistryk@ohsu.edu
Eneida R Nemecek, MD, MS, MBA
- Recruiting
University of California San Francisco
San Francisco, California, 94158
Kevin Magruder, 415-476-3834, Kevin.Magruder@ucsf.edu
Alexis Melton, MD
- Not yet recruiting
Washington University School of Medicine
St Louis, Missouri, 63110
Sheri Kersting, CCRP, skersting@wustl.edu
Shalini Shenoy, MO, MD
Canada5 sites, 4 recruiting
- Recruiting
Alberta Children's Hospital
Calgary, Alberta, T3B 6A8
Debra Rich, Debra.Rich@albertahealthservices.ca
Victor Lewis, MD
- Recruiting
CHU Sainte-Justine
Montreal, Quebec, H3T 1C5
David Godin, david.godin.hsj@ssss.gouv.qc.ca
Henrique Bittencourt, MD, PhD
- Recruiting
McGill University Health Centre
Montreal, Quebec, H4A 3J1
Samira Mezziani, Samira.Mezziani@MUHC.MCGILL.CA
David Mitchell, MD
- Recruiting
BC Children's Hospital
Vancouver, British Columbia, V6H 3N1
Alecia Lim, Alecia.Lim@cw.bc.ca
Kirk R. Schultz, MD
- Active, not recruiting
CancerCare Manitoba
Winnipeg, Manitoba, R3E 0V9
About this study
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)
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.
Read the 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.
- Conditions
- Chronic Graft-versus-Host-Disease, Leukemia, Allogeneic Hematopoietic Stem Cell Transplantation, Blood Cancer, Non-Malignant Hematologic and Lymphocytic Disorder
- Keywords
- cGvHD, HSCT, L-aGvHD, Biomarkers, Blood, Pediatric, Adolescent, Chronic Graft-versus-Host-Disease, Hematopoietic Stem Cell Transplant, Late acute Graft-versus-Host Disease
- Medical subject headings
- Bronchiolitis Obliterans Syndrome, Leukemia, Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Allogeneic HSC Transplant recipients | Five possible patient scenarios are anticipated to occur in those who underwent allogeneic HSCT: * Early event (e.g. death, non-engraftment) occurring before day 100. * No late-acute or chronic GvHD ever develops at any time point in the first year post-transplant (regardless of whether or not classical acute GvHD develops in the first 100 days after transplant). * Early-onset chronic GvHD (including overlap syndrome) occurred before day 60. * Early-onset chronic GvHD (including overlap syndrome) occurred between day 60 and day 100. * Chronic GvHD after Day 100, Late-acute GvHD (de-novo or recurrent) after day 100, or cases of overlap syndrome occurred after day 100. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Day 60 blood sample collection
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.
Measured: Day 60 (+/- 7 days) post-transplant
Day 100 blood sample collection
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.
Measured: Day 100 (+/- 14 days) post-transplant
Onset CvHD blood sample collection
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.
Measured: The day of initial diagnosis
Baseline transplant clinical data collection at Day 0
Baseline Transplant Data Case Report Form to be completed. Clinical data will be used in data analysis.
Measured: Between day 0 (day of transplant) and day +21
Clinical data collection at Day 60
Day 60 Case Report Form to be completed. Clinical data will be used in data analysis.
Measured: Day 60 (+/- 7 days) post-transplant
Clinical data collection at Day 100
Case Report Form to be completed. Clinical data will be used in data analysis.
Measured: Day 100 (+/- 14 days) post-transplant
Clinical data collection at 6 months
Case Report Form to be completed. Clinical data will be used in data analysis.
Measured: 6 Months (+/- 1 month) post-transplant
Clinical data collection at 12 months
Case Report Form to be completed. Clinical data will be used in data analysis.
Measured: 12 Months (+/- 1 month) post-transplant
Clinical data collection at 24 months
Case Report Form to be completed. Clinical data will be used in data analysis.
Measured: 24 Months (+/- 1 month) post-transplant
Clinical data collection at onset of GvHD
Case Report Form to be completed. Clinical data will be used in data analysis.
Measured: At the time of diagnosis
Secondary outcomes (2)
Demonstration of identifiable and reproducible differences in diagnostics of cGvHD and L-aGvHD
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.
Measured: At the end of the study by year 2025
Determination of patient's risk profile and prediction of treatment responses
Utilizing cGvHD specific biomarkers, clinicians will be able to predict patient's treatment responses and chose the more accurate and effective treatment options.
Measured: At the end of the study by year 2025
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2020
- Study start15 Nov 2020
- Primary completionJan 2024 (estimated)
- Study completionJan 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Chronic Graft-versus-Host-DiseaseStudies of the same condition, open and under way.
- More trials run by University of British ColumbiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 350 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of British Columbia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kirk Schultz, University of British Columbia
- Investigators
- Kirk R Schultz, MD, Principal investigator, University of British Columbia / BC Children's Hospital Research InstituteAndrew C Harris, MD, Principal investigator, Memorial Sloan Kettering Cancer Center / Pediatric Stem Cell Transplantation and Cellular Therapies
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04372524
- Sponsor's protocol ID
- H19-02032
- Status last verified
- Dec 2023
- First submitted
- 24 Apr 2020
- Last updated
- 5 Dec 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Schultz KR, Kariminia A, Ng B, Abdossamadi S, Lauener M, Nemecek ER, Wahlstrom JT, Kitko CL, Lewis VA, Schechter T, Jacobsohn DA, Harris AC, Pulsipher MA, Bittencourt H, Choi SW, Caywood EH, Kasow KA, Bhatia M, Oshrine BR, Flower A, Chaudhury S, Coulter D, Chewning JH, Joyce M, Savasan S, Pawlowska AB, Megason GC, Mitchell D, Cheerva AC, Lawitschka A, Azadpour S, Ostroumov E, Subrt P, Halevy A, Mostafavi S, Cuvelier GDE. Immune profile differences between chronic GVHD and late acute GVHD: results of the ABLE/PBMTC 1202 studies. Blood. 2020 Apr 9;135(15):1287-1298. doi: 10.1182/blood.2019003186.
PubMed 32047896Cuvelier GDE, Nemecek ER, Wahlstrom JT, Kitko CL, Lewis VA, Schechter T, Jacobsohn DA, Harris AC, Pulsipher MA, Bittencourt H, Choi SW, Caywood EH, Kasow KA, Bhatia M, Oshrine BR, Flower A, Chaudhury S, Coulter D, Chewning JH, Joyce M, Savasan S, Pawlowska AB, Megason GC, Mitchell D, Cheerva AC, Lawitschka A, West LJ, Pan B, Al Hamarneh YN, Halevy A, Schultz KR. Benefits and challenges with diagnosing chronic and late acute GVHD in children using the NIH consensus criteria. Blood. 2019 Jul 18;134(3):304-316. doi: 10.1182/blood.2019000216. Epub 2019 May 1.
PubMed 31043425