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

• ClinicalTrials.gov Identifier: NCT04372524
• Recruitment Status: Recruiting
• First Posted: May 4, 2020
• Last Update Posted: June 22, 2022
• Sponsor: University of British Columbia
• Information provided by (Responsible Party): Kirk Schultz, University of British Columbia

Study Description

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.

Study Design

• 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

Groups and Cohorts

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.

Outcome Measures

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

Eligibility Criteria

• 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).

Contacts and Locations

Contacts

Contact: Elena Ostroumov, PhD; 604-875-2000 ext 6648; Elena.Ostroumov@bcchr.ca

Contact: Sayeh Abdossamadi, PhD; 604-875-2454; sabdossamadi@bcchr.ca

Locations

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

• 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

More Information

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, Savaşan 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.

• 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
• Last Update Posted: June 22, 2022
• Last Verified: June 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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:

Hematologic Neoplasms; Hematologic Diseases; Graft vs Host Disease; Immune System Diseases; Neoplasms by Site; Neoplasms