Polyomic Biomarker Verification in Adult Chronic Graft-Versus-Host Disease (ABLE3.0/CTTC2201)

Polyomic Biomarker Verification in Adult Chronic Graft-Versus-Host Disease. Applied Biomarkers in Late Effects (ABLE) (ABLE3.0/CTTC2201)

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).

Study Overview

• Status: Recruiting
• Conditions: Leukemia; Allogeneic Hematopoietic Stem Cell Transplantation; Blood Cancer; Chronic Graft-versus-Host-Disease; Non-Malignant Hematologic and Lymphocytic Disorder

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.

• Study Type: Observational
• Enrollment (Estimated): 320

Contacts and Locations

• Study Contact: Name: Elena Ostroumov, PhD; Phone Number: 6648 604-875-2000; Email: elena.ostroumov@bcchr.ca

Study Locations

• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • Not yet recruiting
      • CancerCare Manitoba
      • Contact: Kristjan Paulson, MD
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Not yet recruiting
      • NS Health
      • Contact: Mahmoud Elsawy, MD, MSc
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Not yet recruiting
      • Juravinski Hospital & Cancer Centre
      • Contact: Kylie Lepic, MD
    • London, Ontario, Canada, N6C 2R5
      • Not yet recruiting
      • LHSC: Victoria Hospital
      • Contact: Uday Deotare, MD
    • Toronto, Ontario, Canada, M5G 2C4
      • Recruiting
      • UHN Princess Margaret Cancer Centre
      • Contact: Frank Michelis, MD, PhD
  • Quebec
    • Laval, Quebec, Canada, G1R 2J6
      • Not yet recruiting
      • CHU de Québec - Université Laval
      • Contact: Geneviève Gallagher, MD
    • Montréal, Quebec, Canada, H3H 2R9
      • Not yet recruiting
      • McGill University Health Center
      • Contact: Gizelle Popradi, MDCM
• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63130-4899
      • Recruiting
      • Washington University St. Louis
      • Contact: Iskra Pusic, MD
  • Nebraska
    • Omaha, Nebraska, United States, 68198-5331
      • Recruiting
      • University of Nebraska Medical Center
      • Contact: Vijaya Bhatt, MD
  • Oregon
    • Portland, Oregon, United States, 97239-3098
      • Recruiting
      • Oregon Health & Science University
      • Contact: Arpita Gandhi, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Allogeneic Stem Cell Transplant recipients

Description

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).

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Onset of Early cGvHD	Early chronic GvHD including overlap syndrome	Before Day 100 post-transplant
Onset of cGvHD or L-aGvHD	Chronic GvHD after Day 100, Late acute GvHD (de-novo or recurrent) after Day 100, or cases of overlap syndrome after Day 100	After Day 100 post-transplant
No cGvHD or L-aGvHD	No Chronic or Late-acute GvHD ever develops at any time point in first year post-transplant (regardless of whether or not classical acute GvHD develops in the first 100 days after transplant)	12 months post-transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Early Event (criterium for coming off-study)	A patient will be taken off study if relapse, mortality, non-engraftment or second transplant occurred	Before Day 100 post-transplant

Collaborators and Investigators

• Sponsor: University of British Columbia
• Investigators: Principal Investigator: Kirk R. Schultz, MD, University of British Columbia / BC Children's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2023
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: January 11, 2023
• First Submitted That Met QC Criteria: January 11, 2023
• First Posted (Actual): January 20, 2023

Study Record Updates

• Last Update Posted (Actual): December 8, 2023
• Last Update Submitted That Met QC Criteria: December 2, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Biomarkers; Blood; Immune cells; cGvHD; Allogeneic HSCT; Prognostic / diagnostic algorithm; Adult HSC transplant recipients; Blood cancers
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Bronchial Diseases; Lung Diseases, Obstructive; Bronchitis; Bronchiolitis Obliterans; Bronchiolitis; Organizing Pneumonia; Hematologic Neoplasms; Hematologic Diseases; Graft vs Host Disease; Bronchiolitis Obliterans Syndrome
• Other Study ID Numbers: H22-03310

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No