Primary Graft FailurePhase 1REVEALNCT03541889
REVEAL Biomarkers of Engraftment After Alternative Donor HSCT
A Phase 1 study testing FLT imaging and TK1 blood measurements in people with Primary Graft Failure, run by University of Oklahoma at 4 sites in United States.
Trial summary
The purpose of this study is to find new tests that could help determine if the newly infused bone marrow cells are growing well after bone marrow transplantation or if new bone marrow cells are needed. Read more about this study
- Who is it for?
- Ages 4 to 80 years
- Conditions the study is for
- Primary Graft Failure
- What is being tested?
- FLT imaging and TK1 blood measurements
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 4 sitesUnited States
- Study dates
- 21 Oct 2020to Nov 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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 4 to 80 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- General
- Ability to undergo 18F FLT imaging without sedation
- Patients > 4 years of age and less than 80 years of age at highest risk for graft failure: cord blood HSCT, haplo HSCT, or lack of engraftment by day 28.
- Diagnosed with a condition for which hematopoietic stem cell transplant (HSCT) is standard of care and HSCT is planned (Arm A) or occurred (Arm B)
- In morphologic remission prior to HSCT
- Patient or guardian able to give informed consent
Show all 23Show fewer
- Investigational therapies within past 28 days or planned on protocol are pre-approved by the PI or Site PI
- Karnofsky or Lansky performance status > 60%
- Arm A
- A1 Cord blood recipients: Absence of donor specific antibodies to cord HLA
- Haplo-identical recipients: ≥ 5/10 and < 7/8 allele mismatch donor
- A2- myeloablative Haplo-identical transplant is planned
- A3- reduced intensity Haplo-identical transplant is planned (non-myeloablative is excluded)
- A1- myeloablative or reduced intensity transplant is planned (non-myeloablative is excluded)
- Diagnosed with a condition for which hematopoietic stem cell transplant (HSCT) is standard of care and HSCT is planned
- Total bilirubin < 2.5 mg/dL (unless documented Gilbert's syndrome) and transaminases (ALT and AST) < 5 x the upper limit of normal
- Creatinine clearance or GFR > 60 ml/min/1.73 m2. (performed pre-HSCT)
- FEV1 > 80% pre or post-bronchiolator whichever is higher and DLCO Adj > 70% (performed pre-HSCT if age appropriate) and Sa02 > 94% on room air
- Ejection fraction > 50% (performed pre-HSCT)
- Arm B
- Non-engraftment recipients of HCT with any donor source (related or unrelated): primary graft failure as defined by ANC not > 500 for 3 consecutive days and at least 20 days after HSCT.
- 1-2 cords and >.4/6 match to recipient for each (as per current National Marrow Donor guidelines), with a dose >2 x 10e6 CD34 cells/kg for each cord OR > 5/10 and <7/8 allele mismatch related donor
- Institutional guidelines met for donor suitability
Who cannot join
- History of psychiatric disorder which may compromise compliance with transplant protocol, or which does not allow for appropriate informed consent
- Clinically significant systemic illness with manifestations of significant organ dysfunction which, in the judgment of the PI, or Co-I, would render the patient unlikely to tolerate the protocol therapy or complete the study
- Presence of active malignancy from an organ system other than hematopoietic
- Pregnant or lactating females
- Patients who are unable or unwilling to use effective form (s) of contraception during the course of the study
- Prior history of fluorothymidine allergy or intolerance
- Decline enrolment on CIBMTR research protocol
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Jennifer Holter, MD contact
United States4 sites, 4 recruiting
- Recruiting
University of Michigan
Ann Arbor, Michigan, 48109
Gregory A Yanick, MD
Gregory A Yanick, MD
- Recruiting
Emory University
Atlanta, Georgia, 30322
Kirsten M Williams, MD, kirsten.marie.williams@emory.edu
Kirsten M Williams, MD
- Not yet recruiting
University Hospital of Cleveland UH Seidman Cancer Center
Cleveland, Ohio, 44106
Leland Metheny, MD, Leland.Metheny@UHhospitals.org
Leland Metheny, MD
- Recruiting
University of Oklahoma Health Sciences Center, Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104
Jennifer Holter, MD, 405-271-8777, Jennifer-Holter@ouhsc.edu
IIT Office, SCC-IIT-Office@ouhsc.edu
About this study
Official title: Multi-institutional Prospective Pilot Research of Imaging and Blood Biomarker EValuation of Engraftment After ALlogeneic Hematopoietic Stem Cell Transplantation
The purpose of this study is to find new tests that could help determine if the newly infused bone marrow cells are growing well after bone marrow transplantation or if new bone marrow cells are needed. The Investigator will use FLT imaging, an investigational imaging test, and collect blood samples to investigate whether the cells are growing well.
Read the detailed description
This is a prospective pilot study with primary aim of determining whether investigational FLT imaging can detect and distinguish nonengraftment from delayed engraftment after HSCT in populations at highest risk for graft failure. The investigator will enroll up to 56 patients to achieve 50 evaluable patients undergoing hematopoietic cell transplantation on this trial [5 pediatric and adult recipients of cord blood stem cells (Arm A1), 15 pediatric and adult recipients of myeloablative haplo-identical HSCT (Arm A2), 10 pediatric and adult recipients of reduced intensity haplo-identical HSCT (Arm A3), and 20 recipients of these two stem cell sources who have not engrafted by day 28 (Arm B)]. Should a patient be unable to undergo FLT evaluation after enrollment or relapse in the first 30 days, the patient will be replaced. The planned length of this trial is 7 years and it will be conducted at 4 centers enrolling participants: Emory/Children's Healthcare of Atlanta, University of Oklahoma, University of Michigan, and University Hospitals of Cleveland.
For all pediatric and adult patients undergoing cord blood HSCT, FLT imaging will occur one day prior to HSCT and on days 9 and 28 after HSCT (Arm A1). For recipients of haplo-HSCT, FLT PET/CT imaging will occur one day prior to HSCT and on days 5 or 9 and 28 after HSCT (Arm A2 and A3). Pediatric and adult patients who have not engrafted by day 20 after cord or haplo-identical HSCT will undergo a single FLT image within one week to determine if this scan can identify graft failure versus delayed engraftment (Arm B). All patients will undergo serial peripheral blood evaluation for blood biomarker analysis, including thymidine kinase-1 (TK1). Study endpoints include: 1) detection of nonengraftment with FLT and TK1, 2) development of a model that predicts nonengraftment versus delayed engraftment using FLT and TK1, 3) sensitivity of individual biomarkers to distinguish between graft failure and delayed engraftment, and 4) biology of cord blood and haplo-HSCT engraftment.
For all pediatric and adult patients undergoing cord blood HSCT, three FLT images will be taken: first, one day prior to HSCT and second and third, on days 9 and 28 after HSCT. For recipients of haplo-HSCT, the FLT images will be taken one day prior to HSCT and then on days 5 and 28 after HSCT. Pediatric and adult patients who have not engrafted by day 24 after cord or haplo-identical HSCT will undergo a single FLT PET/CT image within one week, to determine if this scan can identify graft failure versus delayed engraftment. Blood samples will also be collected from all patients for blood biomarker analysis, including thymidine kinase-1 (TK1). Each patient will be in this study for one year.
- Conditions
- Primary Graft Failure
- Being tested
- FLT imaging and TK1 blood measurements
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FLT imaging and TK1 blood measurementsDrug
F18 labeled thymidine PET/CT scans will be performed. Serum measurements of TK1 will be obtained.
| Study group | Role | What they receive |
|---|---|---|
| Cord and haplo imaging cohort | Experimental | For all pediatric and adult patients undergoing cord blood HSCT, FLT PET/CT imaging will occur one day prior to HSCT and on days 9 and 28 after HSCT. For recipients of haplo-HSCT, FLT PET/CT imaging will occur one day prior to HSCT and on days 5 and 28 after HSCT. Receives: Drug: FLT imaging and TK1 blood measurements |
| Nonengrafted cohort | Experimental | Pediatric and adult patients who have not engrafted by day 24 after cord or haplo-identical HSCT will undergo a single FLT PET/CT image within one week to determine if this scan can identify graft failure versus delayed engraftment. Receives: Drug: FLT imaging and TK1 blood measurements |
What is being measured
The primary outcome is the main question the study is designed to answer.
FLT SUV identifies graft failure
To calculate if SUV > 1.2 identifies subclinical engraftment using FLT PET/CT imaging for recipients of cord and haplo-HSCT who have not engrafted within 24 days of HSCT.
Measured: 24-28 days
Secondary outcomes (4)
Map subclinical engraftment in alternative donor HSCT
Use SUV increase in particular medullary spaces to identify the first site of marrow settling after HSCT in alternative donor HSCT
Measured: Day -1 to Day 28 after HSCT
TK1 serum levels identify graft failure
Calculate if TK1 level increases correlate with clinical engraftment
Measured: 24-28 days
Number of patients with CTCAE version 5 events exceeding grade 3 that are possibly, probably, or definitely attributed to the FLT imaging
Safety of FLT in alternative donor HSCT - Calculate the number of patients with CTCAE version 5 events exceeding grade 3 that are possibly, probably, or definitely attributed to the FLT imaging
Measured: Day -1 to Day 28 after HSCT
Other cytokine and chemokine markers of graft failure
Explore other cellular, cytokine, and chemokine markers of subclinical engraftment
Measured: 24-28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 May 2018
- Study start21 Oct 2020
- Primary completion14 Dec 2026 (estimated)
- Study completionNov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary Graft FailureStudies of the same condition, open and under way.
- More trials run by University of OklahomaThe 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
- Interventional
- Phase
- Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Oklahoma
- Sponsor type
- University, hospital or other
- Collaborators
- Emory University, University of Michigan, University Hospitals Cleveland Medical Center, National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor
- Investigators
- Kirsten Williams, MD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03541889
- Sponsor's protocol ID
- OU-SCC-REVEAL
- Other IDs
- 5R01HL146668-04
- Acronym
- REVEAL
- Status last verified
- Aug 2026
- First submitted
- 17 May 2018
- Last updated
- 18 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multi-institutional Prospective Pilot Research of Imaging and Blood Biomarker EValuation of Engraftment After ALlogeneic Hematopoietic Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT03541889
- Acronym / sponsor ID
- REVEAL / OU-SCC-REVEAL
- Conditions
- Primary Graft Failure
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University of OklahomaUniversity, hospital or other
- Collaborators
- Emory University, University of Michigan, University Hospitals Cleveland Medical Center, National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 21 Oct 2020 (actual)
- Primary completion
- 14 Dec 2026 (estimated)
- Study completion
- Nov 2027 (estimated)
- First posted
- 31 May 2018 (actual)
- 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.
The purpose of this study is to find new tests that could help determine if the newly infused bone marrow cells are growing well after bone marrow transplantation or if new bone marrow cells are needed. The Investigator will use FLT imaging, an investigational imaging test, and collect blood samples to investigate whether the cells are growing well.
Detailed description
This is a prospective pilot study with primary aim of determining whether investigational FLT imaging can detect and distinguish nonengraftment from delayed engraftment after HSCT in populations at highest risk for graft failure. The investigator will enroll up to 56 patients to achieve 50 evaluable patients undergoing hematopoietic cell transplantation on this trial [5 pediatric and adult recipients of cord blood stem cells (Arm A1), 15 pediatric and adult recipients of myeloablative haplo-identical HSCT (Arm A2), 10 pediatric and adult recipients of reduced intensity haplo-identical HSCT (Arm A3), and 20 recipients of these two stem cell sources who have not engrafted by day 28 (Arm B)]. Should a patient be unable to undergo FLT evaluation after enrollment or relapse in the first 30 days, the patient will be replaced. The planned length of this trial is 7 years and it will be conducted at 4 centers enrolling participants: Emory/Children's Healthcare of Atlanta, University of Oklahoma, University of Michigan, and University Hospitals of Cleveland.
For all pediatric and adult patients undergoing cord blood HSCT, FLT imaging will occur one day prior to HSCT and on days 9 and 28 after HSCT (Arm A1). For recipients of haplo-HSCT, FLT PET/CT imaging will occur one day prior to HSCT and on days 5 or 9 and 28 after HSCT (Arm A2 and A3). Pediatric and adult patients who have not engrafted by day 20 after cord or haplo-identical HSCT will undergo a single FLT image within one week to determine if this scan can identify graft failure versus delayed engraftment (Arm B). All patients will undergo serial peripheral blood evaluation for blood biomarker analysis, including thymidine kinase-1 (TK1). Study endpoints include: 1) detection of nonengraftment with FLT and TK1, 2) development of a model that predicts nonengraftment versus delayed engraftment using FLT and TK1, 3) sensitivity of individual biomarkers to distinguish between graft failure and delayed engraftment, and 4) biology of cord blood and haplo-HSCT engraftment.
For all pediatric and adult patients undergoing cord blood HSCT, three FLT images will be taken: first, one day prior to HSCT and second and third, on days 9 and 28 after HSCT. For recipients of haplo-HSCT, the FLT images will be taken one day prior to HSCT and then on days 5 and 28 after HSCT. Pediatric and adult patients who have not engrafted by day 24 after cord or haplo-identical HSCT will undergo a single FLT PET/CT image within one week, to determine if this scan can identify graft failure versus delayed engraftment. Blood samples will also be collected from all patients for blood biomarker analysis, including thymidine kinase-1 (TK1). Each patient will be in this study for one year.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cord and haplo imaging cohort | Experimental | Drug: FLT imaging and TK1 blood measurementsFor all pediatric and adult patients undergoing cord blood HSCT, FLT PET/CT imaging will occur one day prior to HSCT and on days 9 and 28 after HSCT. For recipients of haplo-HSCT, FLT PET/CT imaging will occur one day prior to HSCT and on days 5 and 28 after HSCT. |
| Nonengrafted cohort | Experimental | Drug: FLT imaging and TK1 blood measurementsPediatric and adult patients who have not engrafted by day 24 after cord or haplo-identical HSCT will undergo a single FLT PET/CT image within one week to determine if this scan can identify graft failure versus delayed engraftment. |
Who may qualify
- Ages
- 4 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (23 listed)
- General
- Ability to undergo 18F FLT imaging without sedation
- Patients > 4 years of age and less than 80 years of age at highest risk for graft failure: cord blood HSCT, haplo HSCT, or lack of engraftment by day 28.
- Diagnosed with a condition for which hematopoietic stem cell transplant (HSCT) is standard of care and HSCT is planned (Arm A) or occurred (Arm B)
- In morphologic remission prior to HSCT
Key exclusion criteria (7 listed)
- History of psychiatric disorder which may compromise compliance with transplant protocol, or which does not allow for appropriate informed consent
- Clinically significant systemic illness with manifestations of significant organ dysfunction which, in the judgment of the PI, or Co-I, would render the patient unlikely to tolerate the protocol therapy or complete the study
- Presence of active malignancy from an organ system other than hematopoietic
- Pregnant or lactating females
- Patients who are unable or unwilling to use effective form (s) of contraception during the course of the study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FLT imaging and TK1 blood measurementsF18 labeled thymidine PET/CT scans will be performed. Serum measurements of TK1 will be obtained. | Drug | Cord and haplo imaging cohort, Nonengrafted cohort |
Primary outcome
FLT SUV identifies graft failure
Time frame: 24-28 days
To calculate if SUV > 1.2 identifies subclinical engraftment using FLT PET/CT imaging for recipients of cord and haplo-HSCT who have not engrafted within 24 days of HSCT.
4 secondary outcomes
Map subclinical engraftment in alternative donor HSCT
Time frame: Day -1 to Day 28 after HSCT
TK1 serum levels identify graft failure
Time frame: 24-28 days
Number of patients with CTCAE version 5 events exceeding grade 3 that are possibly, probably, or definitely attributed to the FLT imaging
Time frame: Day -1 to Day 28 after HSCT
Other cytokine and chemokine markers of graft failure
Time frame: 24-28 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2026.
- 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.
Jennifer Holter, MD contact
Kirsten Williams, MD principal investigator
Emory University
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing FLT imaging and TK1 blood measurements in people with Primary Graft Failure, run by University of Oklahoma 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?
The sponsor lists 23 inclusion and 7 exclusion criteria. 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: looking for participants now, as of the sponsor's last update on 18 Aug 2026. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kirsten M Williams, MD (404-727-4253, kirsten.marie.williams@emory.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
FLT SUV identifies graft failure (time frame: 24-28 days). 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 18 Aug 2026.