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

Leukemia Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04372524
• Other study ID #: H19-02032
• Status: Recruiting
• Start date: November 15, 2020
• Est. completion date: January 2025

Study information

• Verified date: December 2023
• Source: University of British Columbia
• Contact: Elena Ostroumov, PhD
• Phone: 604-875-2000
• Email: Elena.Ostroumov[@]bcchr.ca
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 350
• Est. completion date: January 2025
• Est. primary completion date: January 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Years to 24 Years

Eligibility

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).

Related Conditions & MeSH terms

• Allogeneic Hematopoietic Stem Cell Transplantation
• Blood Cancer
• Bronchiolitis Obliterans Syndrome
• Chronic Graft-versus-Host-Disease
• Graft vs Host Disease
• Hematologic Diseases
• Hematologic Neoplasms
• Leukemia
• Non-Malignant Hematologic and Lymphocytic Disorder

Locations

Country	Name	City	State
Canada	Alberta Children's Hospital	Calgary	Alberta
Canada	CHU Sainte-Justine	Montréal	Quebec
Canada	McGill University Health Centre	Montréal	Quebec
Canada	BC Children's Hospital	Vancouver	British Columbia
Canada	CancerCare Manitoba	Winnipeg	Manitoba
United States	Emory University School of Medicine	Atlanta	Georgia
United States	Roswell Park Comprehensive Care Center	Buffalo	New York
United States	University of North Carolina	Chapel Hill	North Carolina
United States	Atrium Health Levine Cancer Institute	Charlotte	North Carolina
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Children's Hospital Colorado	Denver	Colorado
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Oregon Health & Science University Knight Cancer Institute	Portland	Oregon
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	University of California San Francisco	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
University of British Columbia

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	6 Month HAPLO blood sample collection	Blood sample from haploidentical transplant recipients who did not develop late-acute or chronic GvHD	6 Months (+/- 1 month) post-transplant
Other	12 Month HAPLO blood sample collection	Blood sample from haploidentical transplant recipients who did not develop late-acute or chronic	12 Months (+/- 1 month) post-transplant
Primary	Day 60 blood sample collection	Validation of prognostic and diagnostic power of cGvHD biomarkers and testing of the biomarker assay performance of Day 60 post-transplant blood sample. Using this algorithm-based assay the investigators will attempt to develop risk assignment for cGvHD and L-aGvHD at Day 60 and determine whether this time point has a similar (or improved) predictive value to the day +100 (+/-14 days). Flow Cytometry and ELISA assays will be used for biomarker measurement.	Day 60 (+/- 7 days) post-transplant
Primary	Day 100 blood sample collection	Validation of prognostic and diagnostic power of cGvHD biomarkers and testing of the biomarker assay performance of Day 100 post-transplant blood sample (diagnostic biomarkers). Using this algorithm-based assay the investigators will attempt to develop risk assignment for cGvHD and L-aGvHD at Day 100. Flow Cytometry and ELISA assays will be used for biomarker measurement.	Day 100 (+/- 14 days) post-transplant
Primary	Onset CvHD blood sample collection	Validation of prognostic and diagnostic power of cGvHD biomarkers and testing of the biomarker assay performance of the GvHD onset blood sample. The investigators will attempt to determine whether biomarkers present at the onset of new late-acte GvHD developing after day +100 (diagnostic biomarkers) or are similar to or different than at the onset of chronic GvHD. Flow Cytometry and ELISA assays will be used for biomarker measurement.	The day of initial diagnosis
Primary	Baseline transplant clinical data collection at Day 0	Baseline Transplant Data Case Report Form to be completed. Clinical data will be used in data analysis.	Between day 0 (day of transplant) and day +21
Primary	Clinical data collection at Day 60	Day 60 Case Report Form to be completed. Clinical data will be used in data analysis.	Day 60 (+/- 7 days) post-transplant
Primary	Clinical data collection at Day 100	Case Report Form to be completed. Clinical data will be used in data analysis.	Day 100 (+/- 14 days) post-transplant
Primary	Clinical data collection at 6 months	Case Report Form to be completed. Clinical data will be used in data analysis.	6 Months (+/- 1 month) post-transplant
Primary	Clinical data collection at 12 months	Case Report Form to be completed. Clinical data will be used in data analysis.	12 Months (+/- 1 month) post-transplant
Primary	Clinical data collection at 24 months	Case Report Form to be completed. Clinical data will be used in data analysis.	24 Months (+/- 1 month) post-transplant
Primary	Clinical data collection at onset of GvHD	Case Report Form to be completed. Clinical data will be used in data analysis.	At the time of diagnosis
Secondary	Demonstration of identifiable and reproducible differences in diagnostics of cGvHD and L-aGvHD	Metrics to measure this outcome will employ the difference in biomarkers (in combination with clinical manifestation) that can be used to discriminate between cGvHD and L-aGvHD and aid clinicians in establishing a more accurate diagnosis. Laboratory procedure and statistical data analysis will be used to achieve this.	At the end of the study by year 2025
Secondary	Determination of patient's risk profile and prediction of treatment responses	Utilizing cGvHD specific biomarkers, clinicians will be able to predict patient's treatment responses and chose the more accurate and effective treatment options.	At the end of the study by year 2025