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Biomarker Verification in Pediatric Chronic GvHD: ABLE 2.0 / PTCTC GVH 1901 Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04372524
Recruitment Status : Recruiting
First Posted : May 4, 2020
Last Update Posted : June 22, 2022
Sponsor:
Information provided by (Responsible Party):
Kirk Schultz, 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.


Condition or disease
Chronic Graft-versus-Host-Disease Leukemia Allogeneic Hematopoietic Stem Cell Transplantation Blood Cancer Non-Malignant Hematologic and Lymphocytic Disorder

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.

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Study Type : Observational
Estimated Enrollment : 350 participants
Observational Model: Cohort
Time Perspective: Cross-Sectional
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


Group/Cohort
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.



Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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 Outcome Measures :
  1. 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.

  2. 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.


Other Outcome Measures:
  1. 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

  2. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 24 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
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.
Criteria

INCLUSION CRITERIA:

  1. Any indication for allogeneic hematopoietic stem cell transplant (malignant or non-malignant)
  2. Age 0 - 24.99 years at the time of transplant (on day 0)
  3. Any conditioning regimen (including myeloablative or reduced-toxicity/reduced-intensity)
  4. Any graft source (bone marrow, peripheral blood, cord blood)
  5. Any graft-versus-host disease prophylaxis strategy, including serotherapy such as ATG or alemtuzumab
  6. Haploidentical transplants, including post-transplant cyclophosphamide and alpha-beta TCR depletion, are allowed

EXCLUSION CRITERIA:

  1. Second or greater allogeneic transplant
  2. Weight 7 kg or less
  3. Pure CD34+ selected haploidentical stem cell transplant (not including CD34 enrichment used in alpha-beta TCR depleted haploidentical transplants, which is allowed)
  4. 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).

Information from the National Library of Medicine

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


Contacts
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Contact: Elena Ostroumov, PhD 604-875-2000 ext 6648 Elena.Ostroumov@bcchr.ca
Contact: Sayeh Abdossamadi, PhD 604-875-2454 sabdossamadi@bcchr.ca

Locations
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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       skersting@wustl.edu   
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       juanita_cuffee@med.unc.edu   
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       mistryk@ohsu.edu   
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       lillian.f.flynn@vumc.org   
Principal Investigator: Carrie L Kitko, MD         
Canada, Alberta
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         
Canada, Manitoba
CancerCare Manitoba Active, not recruiting
Winnipeg, Manitoba, Canada, R3E 0V9
Canada, Quebec
CHU Sainte-Justine Recruiting
Montréal, Quebec, Canada, H3T 1C5
Contact: David Godin       david.godin.hsj@ssss.gouv.qc.ca   
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         
Sponsors and Collaborators
University of British Columbia
Investigators
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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
Publications:
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Responsible Party: Kirk Schultz, Professor of Pediatrics, University of British Columbia
ClinicalTrials.gov Identifier: NCT04372524    
Other Study ID Numbers: H19-02032
First Posted: May 4, 2020    Key Record Dates
Last Update Posted: June 22, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Kirk Schultz, University of British Columbia:
cGvHD
HSCT
L-aGvHD
Biomarkers
Blood
Pediatric
Adolescent
Chronic Graft-versus-Host-Disease
Hematopoietic Stem Cell Transplant
Late acute Graft-versus-Host Disease
Additional relevant MeSH terms:
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Hematologic Neoplasms
Hematologic Diseases
Graft vs Host Disease
Immune System Diseases
Neoplasms by Site
Neoplasms