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

NCT ID: NCT04372524

Last Updated: 2023-12-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

350 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-11-15

Study Completion Date

2025-01-31

Brief Summary

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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.

Detailed Description

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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

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

Keywords

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cGvHD HSCT L-aGvHD Biomarkers Blood Pediatric Adolescent Chronic Graft-versus-Host-Disease Hematopoietic Stem Cell Transplant Late acute Graft-versus-Host Disease

Study Design

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Observational Model Type

COHORT

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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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.

No interventions assigned to this group

Eligibility Criteria

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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).
Minimum Eligible Age

0 Years

Maximum Eligible Age

24 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of British Columbia

OTHER

Sponsor Role lead

Responsible Party

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Kirk Schultz

Professor of Pediatrics

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Kirk R Schultz, MD

Role: PRINCIPAL_INVESTIGATOR

University of British Columbia / BC Children's Hospital Research Institute

Andrew C Harris, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center / Pediatric Stem Cell Transplantation and Cellular Therapies

Locations

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University of California San Francisco

San Francisco, California, United States

Site Status RECRUITING

Children's Hospital Colorado

Denver, Colorado, United States

Site Status RECRUITING

Emory University School of Medicine

Atlanta, Georgia, United States

Site Status NOT_YET_RECRUITING

Washington University School of Medicine

St Louis, Missouri, United States

Site Status NOT_YET_RECRUITING

Roswell Park Comprehensive Care Center

Buffalo, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status RECRUITING

University of North Carolina

Chapel Hill, North Carolina, United States

Site Status NOT_YET_RECRUITING

Atrium Health Levine Cancer Institute

Charlotte, North Carolina, United States

Site Status RECRUITING

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status RECRUITING

Oregon Health & Science University Knight Cancer Institute

Portland, Oregon, United States

Site Status RECRUITING

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status RECRUITING

Alberta Children's Hospital

Calgary, Alberta, Canada

Site Status RECRUITING

BC Children's Hospital

Vancouver, British Columbia, Canada

Site Status RECRUITING

CancerCare Manitoba

Winnipeg, Manitoba, Canada

Site Status ACTIVE_NOT_RECRUITING

CHU Sainte-Justine

Montreal, Quebec, Canada

Site Status RECRUITING

McGill University Health Centre

Montreal, Quebec, Canada

Site Status RECRUITING

Countries

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United States Canada

Central Contacts

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Elena Ostroumov, PhD

Role: CONTACT

Phone: 604-875-2000

Email: [email protected]

Sayeh Abdossamadi, PhD

Role: CONTACT

Phone: 604-875-2454

Email: [email protected]

Facility Contacts

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Kevin Magruder

Role: primary

Kayla Ortiz

Role: primary

Judson Russel

Role: primary

Sheri Kersting, CCRP

Role: primary

Heather Cameron

Role: primary

Chima Elenwune

Role: primary

Juanita Cuffee

Role: primary

Katie Cline

Role: primary

Lori Jewell

Role: primary

Kinjal Mistry

Role: primary

Lillie Flynn

Role: primary

Debra Rich

Role: primary

Alecia Lim

Role: primary

David Godin

Role: primary

Samira Mezziani

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 32047896 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31043425 (View on PubMed)

Other Identifiers

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H19-02032

Identifier Type: -

Identifier Source: org_study_id