Clinical trial NCT02067832: Predictive Biomarkers For Pediatric Chronic Graft-Versus-Host Disease
Official title: Applying Biomarkers to Long-term Effects in Child and Adolescent Cancer Treatment (ABLE Team) - Predictive Biomarkers For Pediatric Chronic Graft-Versus-Host Disease
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Chronic Graft vs Host Disease
Lead sponsor: University of British Columbia
Sponsor class: OTHER
First posted: 2014-02-20
Enrollment: 302
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Recipients and donors of allogeneic hematopoietic stem cell transplantation

Brief summary: Chronic graft-versus-host disease (cGVHD) can be hard to diagnose, difficult to manage and contributes significantly to morbidity and mortality in hematopoietic stem cell transplantation patients.

The research will look into identifying and validating cGVHD biological indicators (=bio-markers) which will be evaluated whether they can predict a future development of the disease.

The study hypothesis is that a number of previously reported cGVHD bio-markers, known to be present at the time of cGVHD diagnosis, will also be present at earlier time points, before cGVHD develops.

Following validation, the bio-markers will be beneficial for finding those patients who are in higher risk to develop cGVHD.

By identifying the higher-risk group, which is more likely to develop cGVHD, a pre-emptive therapy might be applied in order to prevent or reduce the prevalence of the disease.


Eligibility criteria: Inclusion Criteria:

1. Allogeneic hematopoietic stem cell transplantation for any malignant or non-malignant disease.
2. Age 0-17.99 years at the time of transplantation.
3. Bone marrow, peripheral blood stem cell and umbilical cord blood (including single or double cord blood) as the graft source.
4. Any conditioning regimen with any chemotherapy / radiation therapy combination. Haploidentical donor transplants with post-transplant cyclophosphamide are also allowed.
5. Use of serotherapy is permitted.
6. Any graft-versus-host disease prophylaxis is permitted, including post-HSCT cyclophosphamide.
7. If participant weighs between 0-20 kg, participant must be able to provide 15 ml of whole blood at each time point.
8. If participant weighs over 20 kg, participant must be able to provide 1ml/kg of whole blood, up to a maximum of 23 mL for the pre-conditioning sample and 32 mL for samples at day +100, 6-months, 12-months, +/- the cGVHD sample.
9. Written informed consent from parents.
10. Assent from study participant when appropriate.
11. Participation on other clinical trials is acceptable.

Exclusion Criteria:

1. Autologous HSCT.
2. Patients referred to a Bone Marrow Transplant (BMT) center from a non-BMT center, where it is anticipated (at the discretion of the center PI) that adequate follow up according to the rules of this protocol can not be met, including the requirement for a reassessment by the BMT center at the time of cGVHD diagnosis.
3. Ex-vivo T-cell depletion of graft source (e.g. CD34 selection).
4. Second (or greater) allogeneic transplants (first allogeneic transplant where a previous autologous transplant was performed is permitted).
5. Syngeneic transplants.

Primary outcomes:
measure: Identification of predictive bio-markers for pediatric chronic Graft-Versus-Host Disease (cGVHD) in Hematopoietic Stem Cell Transplant (HSCT) recipients
timeFrame: Just before transplant to 12 months post transplant or until diagnosis of cGVHD if precede the 12 months
Secondary outcomes:
measure: Validation of "predictive" cGVHD bio-markers
timeFrame: Measure will be assessed following the submission of all samples. During the last year of the study (Oct. 2016 - Sept. 2017)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Children's of Alabama
state: Alabama
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Medical Center
state: California
city: San Francisco
country: United States
facility: UCSF Benioff Children's Hospital
state: California
city: Wilmington
country: United States
facility: Nemours A. I. DuPont Hospital for Children
state: Delaware
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Jacksonville
country: United States
facility: Nemours Children's Clinic
state: Florida
city: Saint Petersburg
country: United States
facility: All Children's Hospital
state: Florida
city: Chicago
country: United States
facility: Ann and Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Ann Arbor
country: United States
facility: C S Mott Children's Hospital The University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Children's Hospital of Michigan
state: Michigan
city: Jackson
country: United States
facility: Blair E. Batson Hospital for Children
state: Mississippi
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: New York
country: United States
facility: Morgan Stanley Children's Hospital
state: New York
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Salt Lake City
country: United States
facility: Utah Primary Children's Medical Center
state: Utah
city: Vienna
country: Austria
facility: ST.Anna Children's Hospital
city: Calgary
country: Canada
facility: Alberta Children's Hospital
state: Alberta
city: Vancouver
country: Canada
facility: University of British Columbia - BC Children's Hospital
state: British Columbia
city: Winnipeg
country: Canada
facility: University of Manitoba
state: Manitoba
city: Toronto
country: Canada
facility: Hospital for Sick Children
state: Ontario
city: Montreal
country: Canada
facility: Montreal Children's Hospital
state: Quebec
city: Montreal
country: Canada
facility: The Sainte-Justine University Hospital Centre
state: Quebec
Study officials:
affiliation: University of Manitoba
name: Geoff Cuvelier, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of British Columbia
name: Kirk R Schultz, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Subburaj D, Ng B, Kariminia A, Abdossamadi S, Lauener M, Nemecek ER, Rozmus J, Kharbanda S, Kitko CL, Lewis VA, Schechter-Finklestein T, Jacobsohn DA, Harris AC, Pulsipher MA, Bittencourt H, Choi SW, Caywood EH, Kasow KA, Bhatia M, Oshrine BR, Coulter D, Chewning JH, Joyce M, Pawlowska AB, Megason GC, Lawitschka A, Ostroumov E, Klein Geltink R, Cuvelier GDE, Schultz KR. Metabolomic identification of alpha-ketoglutaric acid elevation in pediatric chronic graft-versus-host disease. Blood. 2022 Jan 13;139(2):287-299. doi: 10.1182/blood.2021013244.