Hematopoietic Stem Cell TransplantationNCT02414113
Study for the Evaluation of a GVHD Negative Outcome Score (GNOS) in Matched Unrelated or Haploidentical Hematopoietic Stem Cell Transplant
An observational study of Hematopoietic Stem Cell Transplantation and Stem Cell Transplantation, Hematopoietic, run by Washington University School of Medicine at 4 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Hematopoietic Stem Cell Transplantation, Stem Cell Transplantation, Hematopoietic, Transplantation, Hematopoietic Stem Cell
- How many people
- 113 participants
- Where
- 4 sitesUnited States
- Study dates
- 25 Mar 2015to 21 Jan 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
UNC Hospitals
Chapel Hill, North Carolina, 27516
James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
Duke University Medical Center
Durham, North Carolina, 27710
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
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
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.
Read the 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.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Low GNOS donors | Not described | |
| High GNOS donors | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
-Overall survival (OS) is defined as the date of transplant to the date of death from any cause.
Measured: 3 months
Performance of 4 pre-defined GNOS models
- The main variables' association of interest, for any of the 4 outcome predictive models being employed, is recipient aGVHD Grades {0, I, II} exclusive-or Grades {III-IV} vs. donor GNOS level. The analyses will be done separately for each of the 4 different outcome predictive models that have been employed in the study.
- The GNOS values from each of 4 models will be determined by PBD and will be kept confidential and blinded from the investigators. PBD will not know the recipient health data (GVHD occurrence, PFS, OS, etc.) when the GNOs analysis is performed. Thus, a given donor's GNOS values from the 4 different models and the corresponding recipient's outcomes will not be correlated until after unblinding.
Measured: 100 days after HSCT
Relapse rates after HSCTs performed with high GNOS versus low GNOS donors
-A patient will be considered relapsed when there is a recurrence of the original malignant disease after transplantation
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2015 (estimated)
- Study start25 Mar 2015
- Primary completion29 Apr 2020
- Study completion21 Jan 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hematopoietic Stem Cell TransplantationStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 113 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Predictive BioDiagnostics, LLC, National Marrow Donor Program
- Responsible party
- Sponsor
- Investigators
- Mark A Schroeder, M.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02414113
- Sponsor's protocol ID
- 201312100
- Status last verified
- Feb 2021
- First submitted
- 7 Apr 2015
- Last updated
- 4 Feb 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02414113
- Acronym / sponsor ID
- 201312100
- Conditions
- Hematopoietic Stem Cell Transplantation, Stem Cell Transplantation, Hematopoietic, Transplantation, Hematopoietic Stem Cell
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 113 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- Predictive BioDiagnostics, LLC, National Marrow Donor Program
- Study start
- 25 Mar 2015 (actual)
- Primary completion
- 29 Apr 2020 (actual)
- Study completion
- 21 Jan 2021 (actual)
- First posted
- 10 Apr 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Low GNOS donors | – | – |
| High GNOS donors | – | – |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Matched unrelated hematopoietic stem cell transplant recipients
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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
Time frame: 100 days after HSCT
* "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.
3 secondary outcomes
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
Time frame: 3 months
Performance of 4 pre-defined GNOS models
Time frame: 100 days after HSCT
Relapse rates after HSCTs performed with high GNOS versus low GNOS donors
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2021.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark A Schroeder, M.D. principal investigator
Washington University School of Medicine
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hematopoietic Stem Cell Transplantation and Stem Cell Transplantation, Hematopoietic, run by Washington University School of Medicine at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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 (time frame: 100 days after HSCT). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2021.