Trial Title:
Polyomic Biomarker Verification in Adult Chronic Graft-Versus-Host Disease (ABLE3.0/CTTC2201)
NCT ID:
NCT05692713
Condition:
Chronic Graft-versus-Host-Disease
Allogeneic Hematopoietic Stem Cell Transplantation
Leukemia
Blood Cancer
Non-Malignant Hematologic and Lymphocytic Disorder
Conditions: Official terms:
Hematologic Neoplasms
Bronchiolitis Obliterans Syndrome
Hematologic Diseases
Graft vs Host Disease
Conditions: Keywords:
cGvHD
Biomarkers
Blood
Immune cells
Prognostic / diagnostic algorithm
Adult HSC transplant recipients
Blood cancers
Allogeneic HSCT
Study type:
Observational [Patient Registry]
Overall status:
Recruiting
Study design:
Time perspective:
Prospective
Summary:
Chronic graft-versus-host disease (cGvHD) is one of the most serious complications
following BMT (Bone Marrow Transplantation). cGvHD occurs when donor immune cells
"attack" the tissues and organs of the person receiving the BMT. cGvHD can be difficult
to treat once it is established leading to poor quality of life for recipients of a BMT.
The goal of this study is to determine if, by using biomarkers, the investigators can
predict which patients are at the highest risk of developing cGvHD after BMT, before
cGvHD develops.
The ABLE3.0 / CTTC 2201 study will validate and potentially refine the initial predictive
biomarker algorithm developed from the original ABLE/PBTMC 1202 study (ABLE1.0), allowing
clinicians the ability to pre-emptively predict their patient's future risk of developing
both late-acute and chronic GvHD.
This will provide the foundation for the later development of clinical trials aimed at
reducing immune suppression quicker after transplant for low-risk patients (<10% risk)
and justifying more intensive approaches such as pre-emptive treatments before the onset
of chronic GvHD in high-risk patients (>45% risk).
Detailed description:
320 adult transplant recipients will be enrolled in this study. The investigators will
not recruit healthy participants. Only those undergoing treatments from blood cancers and
will be having the transplant procedure will be offered to participate in this study. The
control participant group will be determined 12 months post-transplant. This group will
consist of those participants who did not develop either chronic or late acute GvHD one
year after transplantation.
The investigators will be enrolling allogeneic HCT patients before transplant up through
Day -1, following these patients prospectively until 12-months post-transplant for the
development of all forms of GvHD - classical acute (aGvHD), late acute (L-aGvHD), and
chronic (cGvHD), collecting blood samples and clinical data at day +60, day +100, and at
the onset of either L-aGvHD or chronic GvHD (but not classical acute GvHD before day
+100). Two more blood samples and clinical data will be collected from transplant
recipients who never developed any chronic or late-acute GVHD at the 6- and 12-month
post-transplant time points. Case Report Forms (CRFs) will be completed on the REDCap
platform.
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 12-months post-transplant to document
new cGvHD manifestations, severity, and response to therapy.
A blood sample will not be collected and a CRF will not be completed if classical acute
GvHD occurs before Day 100. Staging and grading of classical acute GvHD however will
occur on the main case report forms.
On average, patients will have up to 4 blood samples drawn over the course of 1-year
post-transplant, depending upon their overall scenario, event and GvHD status.
For clinicians and site PIs, the primary responsibility will be monitoring patients for
the development of all forms of GvHD (classical acute, late acute, and chronic GvHD),
including accurate documentation, and near real-time reporting of detailed clinical data
capture of staging / grading / clinical features /severity and responses to therapy for
patients with late-acute and chronic GvHD.
Blood samples drawn from patients will be shipped to the Schultz Laboratory in Vancouver,
BC, Canada, processed and analyzed for cGvHD biomarkers. Cell phenotyping by flow
cytometry will be carried out on whole blood. Plasma will be used in ELISA, metabolomic
analysis and enzymatic assays. Blood cells will be used for B- and T- cell receptors
research. A statistical validation of the previously developed pediatric risk predictor
in adult population will be be performed based on the estimated overall frequency of
cGvHD at 20% or patients.
Criteria for eligibility:
Study pop:
Allogeneic Stem Cell Transplant recipients
Sampling method:
Probability Sample
Criteria:
INCLUSION CRITERIA:
1. Any indication for allogeneic hematopoietic stem cell transplant (malignant and
nonmalignant);
2. Age >18 years (those who reached the age of majority) 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 GvHD 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. Age < 18 years (or under the age of majority) at the time of consent;
2. Second or greater allogeneic transplant;
3. Pure CD34+ selected stem cell grafts (not including C34+ cell enrichment used in
alpha-beta TCR depleted haploidentical grafts, which are 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).
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Washington University St. Louis
Address:
City:
Saint Louis
Zip:
63130-4899
Country:
United States
Status:
Recruiting
Contact:
Last name:
Iskra Pusic, MD
Facility:
Name:
University of Nebraska Medical Center
Address:
City:
Omaha
Zip:
68198-5331
Country:
United States
Status:
Recruiting
Contact:
Last name:
Vijaya Bhatt, MD
Facility:
Name:
Oregon Health & Science University
Address:
City:
Portland
Zip:
97239-3098
Country:
United States
Status:
Recruiting
Contact:
Last name:
Arpita Gandhi, MD
Facility:
Name:
CancerCare Manitoba
Address:
City:
Winnipeg
Zip:
R3E 0V9
Country:
Canada
Status:
Not yet recruiting
Contact:
Last name:
Kristjan Paulson, MD
Facility:
Name:
NS Health
Address:
City:
Halifax
Zip:
B3H 2Y9
Country:
Canada
Status:
Not yet recruiting
Contact:
Last name:
Mahmoud Elsawy, MD, MSc
Facility:
Name:
Juravinski Hospital & Cancer Centre
Address:
City:
Hamilton
Zip:
L8V 5C2
Country:
Canada
Status:
Not yet recruiting
Contact:
Last name:
Kylie Lepic, MD
Facility:
Name:
LHSC: Victoria Hospital
Address:
City:
London
Zip:
N6C 2R5
Country:
Canada
Status:
Not yet recruiting
Contact:
Last name:
Uday Deotare, MD
Facility:
Name:
UHN Princess Margaret Cancer Centre
Address:
City:
Toronto
Zip:
M5G 2C4
Country:
Canada
Status:
Recruiting
Contact:
Last name:
Frank Michelis, MD, PhD
Facility:
Name:
CHU de Québec - Université Laval
Address:
City:
Laval
Zip:
G1R 2J6
Country:
Canada
Status:
Not yet recruiting
Contact:
Last name:
Geneviève Gallagher, MD
Facility:
Name:
McGill University Health Center
Address:
City:
Montréal
Zip:
H3H 2R9
Country:
Canada
Status:
Not yet recruiting
Contact:
Last name:
Gizelle Popradi, MDCM
Start date:
July 1, 2023
Completion date:
June 30, 2025
Lead sponsor:
Agency:
University of British Columbia
Agency class:
Other
Source:
University of British Columbia
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05692713
