Clinical trial NCT04372524: Biomarker Verification in Pediatric Chronic GvHD: ABLE 2.0 / PTCTC GVH 1901 Study
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)
Study type: OBSERVATIONAL
Overall status: RECRUITING
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
Lead sponsor: University of British Columbia
Sponsor class: OTHER
First posted: 2020-05-04
Enrollment: 350
Sex: ALL
Minimum age (years): 0
Maximum age (years): 24
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
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.

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.

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.

Eligibility 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).

Primary outcomes:
measure: Day 60 blood sample collection
timeFrame: Day 60 (+/- 7 days) post-transplant
measure: Day 100 blood sample collection
timeFrame: Day 100 (+/- 14 days) post-transplant
measure: Onset CvHD blood sample collection
timeFrame: The day of initial diagnosis
measure: Baseline transplant clinical data collection at Day 0
timeFrame: Between day 0 (day of transplant) and day +21
measure: Clinical data collection at Day 60
timeFrame: Day 60 (+/- 7 days) post-transplant
measure: Clinical data collection at Day 100
timeFrame: Day 100 (+/- 14 days) post-transplant
measure: Clinical data collection at 6 months
timeFrame: 6 Months (+/- 1 month) post-transplant
measure: Clinical data collection at 12 months
timeFrame: 12 Months (+/- 1 month) post-transplant
measure: Clinical data collection at 24 months
timeFrame: 24 Months (+/- 1 month) post-transplant
measure: Clinical data collection at onset of GvHD
timeFrame: At the time of diagnosis
Secondary outcomes:
measure: Demonstration of identifiable and reproducible differences in diagnostics of cGvHD and L-aGvHD
timeFrame: At the end of the study by year 2025
measure: Determination of patient's risk profile and prediction of treatment responses
timeFrame: At the end of the study by year 2025
Other outcomes:
measure: 6 Month HAPLO blood sample collection
timeFrame: 6 Months (+/- 1 month) post-transplant
measure: 12 Month HAPLO blood sample collection
timeFrame: 12 Months (+/- 1 month) post-transplant
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Denver
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Buffalo
country: United States
facility: Roswell Park Comprehensive Care Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Charlotte
country: United States
facility: Atrium Health Levine Cancer Institute
state: North Carolina
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University Knight Cancer Institute
state: Oregon
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Calgary
country: Canada
facility: Alberta Children's Hospital
state: Alberta
city: Vancouver
country: Canada
facility: BC Children's Hospital
state: British Columbia
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Montréal
country: Canada
facility: CHU Sainte-Justine
state: Quebec
city: Montréal
country: Canada
facility: McGill University Health Centre
state: Quebec
Study officials:
affiliation: University of British Columbia / BC Children's Hospital Research Institute
name: Kirk R Schultz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Memorial Sloan Kettering Cancer Center / Pediatric Stem Cell Transplantation and Cellular Therapies
name: Andrew C Harris, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.