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

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.

Study Overview

• Status: Recruiting
• Conditions: Leukemia; Allogeneic Hematopoietic Stem Cell Transplantation; Blood Cancer; Chronic Graft-versus-Host-Disease; 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.

• Study Type: Observational
• Enrollment (Estimated): 350

Contacts and Locations

• Study Contact: Name: Elena Ostroumov, PhD; Phone Number: 6648 604-875-2000; Email: elena.ostroumov@bcchr.ca
• Study Contact Backup: Name: Sayeh Abdossamadi, PhD; Phone Number: 604-875-2454; Email: sabdossamadi@bcchr.ca

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3B 6A8
      • Recruiting
      • Alberta Children's Hospital
      • Contact: Debra Rich; Email: Debra.Rich@albertahealthservices.ca
      • Principal Investigator: Victor Lewis, MD
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H 3N1
      • Recruiting
      • BC Children's Hospital
      • Contact: Alecia Lim; Email: Alecia.Lim@cw.bc.ca
      • Principal Investigator: Kirk R. Schultz, MD
      • Sub-Investigator: Jacob Rozmus, MD, PhD
      • Sub-Investigator: Amanda Li, MD, MSc
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • Active, not recruiting
      • CancerCare Manitoba
  • Quebec
    • Montréal, Quebec, Canada, H4A 3J1
      • Recruiting
      • McGill University Health Centre
      • Contact: Samira Mezziani; Email: Samira.Mezziani@MUHC.MCGILL.CA
      • Principal Investigator: David Mitchell, MD
    • Montréal, Quebec, Canada, H3T 1C5
      • Recruiting
      • CHU Sainte-Justine
      • Contact: David Godin; Email: david.godin.hsj@ssss.gouv.qc.ca
      • Principal Investigator: Henrique Bittencourt, MD, PhD
• United States
  • California
    • San Francisco, California, United States, 94158
      • Recruiting
      • University of California San Francisco
      • Contact: Kevin Magruder; Phone Number: 415-476-3834; Email: Kevin.Magruder@ucsf.edu
      • Principal Investigator: Alexis Melton, MD
  • Colorado
    • Denver, Colorado, United States, 80045
      • Recruiting
      • Children's Hospital Colorado
      • Principal Investigator: Amy Keating, MD
      • Contact: Kayla Ortiz; Email: Kayla.Pacheco@childrenscolorado.org
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Not yet recruiting
      • Emory University School of Medicine
      • Contact: Judson Russel; Email: Judson.Russell@choa.org
      • Principal Investigator: Muna Qayed, MD, MsCR
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Not yet recruiting
      • Washington University School of Medicine
      • Contact: Sheri Kersting, CCRP; Email: skersting@wustl.edu
      • Principal Investigator: Shalini Shenoy, MO, MD
  • New York
    • Buffalo, New York, United States, 14263
      • Recruiting
      • Roswell Park Comprehensive Care Center
      • Contact: Heather Cameron; Phone Number: 716-845-1780; Email: Heather.Cameron@RoswellPark.org
      • Principal Investigator: Nataliya Prokopenko Buxbaum, MD
    • New York, New York, United States, 10174
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
      • Contact: Chima Elenwune; Email: ElenwunC@mskcc.org
      • Principal Investigator: Andrew C Harris, MD
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Not yet recruiting
      • University of North Carolina
      • Contact: Juanita Cuffee; Email: juanita_cuffee@med.unc.edu
      • Principal Investigator: Kimberly A Kasow, DO
    • Charlotte, North Carolina, United States, 28203
      • Recruiting
      • Atrium Health Levine Cancer Institute
      • Contact: Katie Cline; Email: Katie.Cline@atriumhealth.org
      • Principal Investigator: Michael W Kent, MD
  • Ohio
    • Columbus, Ohio, United States, 43205-2664
      • Recruiting
      • Nationwide Children's Hospital
      • Contact: Lori Jewell; Email: lori.jewell@nationwidechildrens.org
      • Principal Investigator: Rajinder Bajwa, MD
  • Oregon
    • Portland, Oregon, United States, 97239-3098
      • Recruiting
      • Oregon Health & Science University Knight Cancer Institute
      • Contact: Kinjal Mistry; Email: mistryk@ohsu.edu
      • Principal Investigator: Eneida R Nemecek, MD, MS, MBA
  • Tennessee
    • Nashville, Tennessee, United States, 37232-6311
      • Recruiting
      • Vanderbilt University Medical Center
      • Principal Investigator: Carrie L Kitko, MD
      • Contact: Lillie Flynn; Email: lillian.f.flynn@vumc.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 24 years (Child, Adult)
• 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.

Description

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).

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

1

Cohorts and Interventions

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	At the time of diagnosis

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	At the end of the study by year 2025

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
6 Month HAPLO blood sample collection	Blood sample from haploidentical transplant recipients who did not develop late-acute or chronic GvHD	6 Months (+/- 1 month) post-transplant
12 Month HAPLO blood sample collection	Blood sample from haploidentical transplant recipients who did not develop late-acute or chronic	12 Months (+/- 1 month) post-transplant

Collaborators and Investigators

• Sponsor: University of British Columbia
• Investigators: 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 and helpful links

General 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.
• Cuvelier 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2020
• Primary Completion (Estimated): January 1, 2024
• Study Completion (Estimated): January 1, 2025

Study Registration Dates

• First Submitted: April 24, 2020
• First Submitted That Met QC Criteria: April 29, 2020
• First Posted (Actual): May 4, 2020

Study Record Updates

• Last Update Posted (Actual): December 5, 2023
• Last Update Submitted That Met QC Criteria: December 2, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Adolescent; Pediatric; Hematopoietic Stem Cell Transplant; Biomarkers; Blood; HSCT; cGvHD; L-aGvHD; Chronic Graft-versus-Host-Disease; Late acute Graft-versus-Host Disease
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Bronchial Diseases; Lung Diseases, Obstructive; Bronchitis; Bronchiolitis Obliterans; Bronchiolitis; Organizing Pneumonia; Hematologic Neoplasms; Hematologic Diseases; Graft vs Host Disease; Bronchiolitis Obliterans Syndrome
• Other Study ID Numbers: H19-02032

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No