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

NCT04372524 | Unknown

• 1 other identifier: H19-02032
• Study Type: observational
• Target: 350
• Locations: 2 countries
• Sites: 16

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.

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

Outcome Measures

Primary Outcomes (10)

• 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 Outcomes (2)

• Demonstration of identifiable and reproducible differences in diagnostics of cGvHD and L-aGvHD

  At the end of the study by year 2025

• Determination of patient's risk profile and prediction of treatment responses

  At the end of the study by year 2025

Other Outcomes (2)

• 6 Month HAPLO blood sample collection

  6 Months (+/- 1 month) post-transplant

• 12 Month HAPLO blood sample collection

  12 Months (+/- 1 month) post-transplant

Study Arms (1)

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.

Eligibility Criteria

• Age: 0 Years - 24 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• University of British Columbia: lead

Study Sites (16)

University of California San Francisco

San Francisco, California, 94158, United States

RECRUITING

Children's Hospital Colorado

Denver, Colorado, 80045, United States

RECRUITING

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

NOT YET RECRUITING

Washington University School of Medicine

St Louis, Missouri, 63110, United States

NOT YET RECRUITING

Roswell Park Comprehensive Care Center

Buffalo, New York, 14263, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10174, United States

RECRUITING

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

NOT YET RECRUITING

Atrium Health Levine Cancer Institute

Charlotte, North Carolina, 28203, United States

RECRUITING

Nationwide Children's Hospital

Columbus, Ohio, 43205-2664, United States

RECRUITING

Oregon Health & Science University Knight Cancer Institute

Portland, Oregon, 97239-3098, United States

RECRUITING

Vanderbilt University Medical Center

Nashville, Tennessee, 37232-6311, United States

RECRUITING

Alberta Children's Hospital

Calgary, Alberta, T3B 6A8, Canada

RECRUITING

BC Children's Hospital

Vancouver, British Columbia, V6H 3N1, Canada

RECRUITING

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

ACTIVE NOT RECRUITING

CHU Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada

RECRUITING

McGill University Health Centre

Montreal, Quebec, H4A 3J1, Canada

RECRUITING

Related Publications (2)

• 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.

  PMID: 32047896 BACKGROUND

• 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.

  PMID: 31043425 BACKGROUND

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome; Leukemia; Hematologic Neoplasms

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms by Site

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Elena Ostroumov, PhD

CONTACT

604-875-2000; Elena.Ostroumov@bcchr.ca

Sayeh Abdossamadi, PhD

CONTACT

604-875-2454; sabdossamadi@bcchr.ca

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics

Study Record Dates

• First Submitted: April 24, 2020
• First Posted: May 4, 2020
• Study Start: November 15, 2020
• Primary Completion: January 1, 2024
• Study Completion: January 1, 2025
• Last Updated: December 5, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (11); CA (5)