Clinical trial NCT02414113: Study for the Evaluation of a GVHD Negative Outcome Score (GNOS) in Matched Unrelated or Haploidentical Hematopoietic Stem Cell Transplant
Official title: A Blinded, Prospective Non-Interventional Observational Study for the Evaluation of a GVHD Negative Outcome Score (GNOS) in Matched Unrelated or Haploidentical Hematopoietic Stem Cell Transplant
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hematopoietic Stem Cell Transplantation
Stem Cell Transplantation, Hematopoietic
Transplantation, Hematopoietic Stem Cell
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: Predictive BioDiagnostics, LLC
name: National Marrow Donor Program
First posted: 2015-04-10
Enrollment: 113
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Matched unrelated hematopoietic stem cell transplant recipients

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.

Detailed description: Enrollment of the recipient will occur prior to the unrelated donor search or haploidentical donor identification.

FOR UNRELATED DONORS:

When the unrelated donor search is formalized, the study team will submit a study participation request document to the NMDP for all potential donors that are being evaluated for an enrolled recipient. These documents will be relayed to the appropriate donor centers by the NMDP. This document informs the donor center that the potential donor's participation in this trial is being requested. The donor center then will approach the potential donor about participation in the trial. If the potential donor consents to participate, the required donor study samples will be obtained and shipped to the appropriate labs. This will conclude the potential donor's physical participation in the trial. The donor consent will be kept at the donor center and will not be provided to the investigator.

FOR HAPLOIDENTICAL DONORS:

Haploidentical donors will be identified by the transplant team caring for the recipient, and will follow the site's standard procedures for identification, HLA typing, and medical clearance for stem cell donation. Haploidentical donors will be approached by the transplant team or the study coordinator about participation in the trial. If the potential donor consents to participate, the required donor study samples will be obtained and shipped to the appropriate lab for processing prior to the start of growth factor for stem cell mobilization or prior to stem cell collection via bone marrow harvest.

FOR ALL DONORS:

At the time of HLA confirmatory typing, 24 mL of whole blood will be collected from donors.

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: 100 days after HSCT
Secondary outcomes:
measure: 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
timeFrame: 3 months
measure: Performance of 4 pre-defined GNOS models
timeFrame: 100 days after HSCT
measure: Relapse rates after HSCTs performed with high GNOS versus low GNOS donors
timeFrame: 1 year
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Chapel Hill
country: United States
facility: UNC Hospitals
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Columbus
country: United States
facility: James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Washington University School of Medicine
name: Mark A Schroeder, M.D.
role: PRINCIPAL_INVESTIGATOR
References: