Study for the Evaluation of a GVHD Negative Outcome Score (GNOS) in Matched Unrelated or Haploidentical Hematopoietic Stem Cell Transplant

NCT02414113 | Completed

• 1 other identifier: 201312100
• Study Type: observational
• Target: 113
• Locations: 1 country
• Sites: 4

Brief Summary

Before considering high-GVHD Negative Outcome Score (GNOS) donor selection for routine clinical practice, this blinded prospective study will be carried out for assessment of severe GVHD (graft-versus-host-disease) reduction associated with selecting high-GNOS donors for allogeneic hematopoietic peripheral blood stem cell transplant. The objective of this prospective study is to show: (a) that GVHD reductions and donor availabilities as observed in the retrospective studies also apply to prospective samples that are collected and processed from on-going matched unrelated transplants, and (b) that high-GNOS donor selection readily fits into today's donor selection process, such as to facilitate access to the benefits of GVHD reduction. The prospective study is designed to be blinded, and will not involve specific donor selection nor any influence on clinical management or decision making by application of the GNOS technology. To determine if some GNOS models perform better than others across different clinical centers, or across different recipient / donor attributes, 4 different specific GNOS models will be evaluated. Bootstrap computational analyses have been carried out on the retrospective data for the 4 GNOS models and will be tested and validated in this prospective study.

Conditions

Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation, Hematopoietic; Transplantation, Hematopoietic Stem Cell

Outcome Measures

Primary Outcomes (1)

• Rates of grade III-IV aGVHD (acute graft-versus-host disease) in hematopoietic stem cell transplantation (HSCT) performed with high GNOS versus low GNOS donors

  * "GNOS" refers to PBD's proprietary "GVHD Negative Outcome Score" technology for reduction of grades III \& IV aGVHD through donor selection. GNOS is a gene expression-based signature of lower donor allo-reactivity such that transplanted cells from donors displaying higher GNOS will exhibit less allo-reactivity against recipient tissues, therefore decreasing the incidence of severe GVHD. GNOS is determined from pre-transplant, pre-mobilization gene expression profiling of donor CD4 cells from a blood draw. * Incidence and severity of acute GVHD will be assessed based on the modified Glucksberg criteria and Seattle criteria. Attempts should be made to confirm the diagnosis pathologically by biopsy of target organ(s) as per standard of care.

  100 days after HSCT

Secondary Outcomes (3)

• Overall survival in HSCT performed with high GNOS versus low GNOS donor who experienced Grades 0-II and Grades III-IV aGVHD during the first 100 days after HSCT

  3 months

• Performance of 4 pre-defined GNOS models

  100 days after HSCT

• Relapse rates after HSCTs performed with high GNOS versus low GNOS donors

  1 year

Study Arms (2)

Low GNOS donors

High GNOS donors

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Matched unrelated hematopoietic stem cell transplant recipients

Eligibility Criteria Prior to Unrelated Donor Search / Haploidentical Donor Identification: * Recipient must be between 18 and 70 years of age, inclusive * Recipient must be undergoing unrelated or haploidentical stem cell donor search with one or more potential donors being requested for confirmatory typing and study samples. * Recipient must be able to understand and willing to sign written informed consent document Eligibility Criteria on Day 0: * Selected donor must have agreed to participate in the trial and samples for GNOS must have been received and processed. * If MUD donor, selected donor must not be a C-antigen mismatch with the recipient (C-allele mismatch donor-recipient pairs are eligible). * Recipient must not have received alemtuzumab as part of stem cell conditioning regimen. * Recipient must not undergo transplantation with ex vivo T-cell depleted stem cells. * If MUD donor, recipient must receive a myeloblative stem cell conditioning (MAC) regimen per CIBMTR (Center for International Blood and Marrow Transplant Research) criteria. Patients that receive only low intensity, non-myeloablative conditioning regimen will be excluded. * If haploidentical donor, recipient must receive standard MAC or RIC-conditioning with post-transplant Cytoxan GVHD prophylaxis given on Days +3 and +4. Enrollment will occur prior to the unrelated donor search. Following donor selection, if the recipient does not meet the eligibility criteria listed for Day 0 or if the recipient does not proceed to stem cell transplantation within 12 months of enrollment, the donor/recipient pair will be non-evaluable for the study objectives. Non-evaluable donor/recipient pairs will be removed from trial and replaced.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Predictive BioDiagnostics, LLC: collaborator
• National Marrow Donor Program: collaborator

Study Sites (4)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

UNC Hospitals

Chapel Hill, North Carolina, 27516, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Biospecimen

Retention: SAMPLES WITH DNA

-At the time of HLA confirmatory typing, 24 mL of whole blood will be collected from all potential donors who agree to participate.

Study Officials

• Mark A Schroeder, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 7, 2015
• First Posted: April 10, 2015
• Study Start: March 25, 2015
• Primary Completion: April 29, 2020
• Study Completion: January 21, 2021
• Last Updated: February 4, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)