Imaging and Blood Tests for Graft Failure Detection

(REVEAL Trial)

Recruiting at 4 trial locations

Overseen By Jennifer Holter, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Oklahoma

Disqualifiers: Psychiatric disorder, Organ dysfunction, Active malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 5

56 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to develop new tests to assess the effectiveness of bone marrow transplants. Researchers will use a special imaging test called FLT imaging (Fluorothymidine imaging) and collect blood samples to monitor the growth of transplanted cells. The trial includes different groups, such as those who recently underwent a specific type of bone marrow transplant and those who haven't fully recovered yet. Suitable candidates have either planned or completed a hematopoietic stem cell transplant (HSCT) and are at high risk for graft failure. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

Do I need to stop my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What prior data suggests that FLT imaging and TK1 blood measurements are safe?

Research shows that FLT imaging, used in this trial, is generally well-tolerated. In past studies, FLT PET imaging safely detected early cell growth during bone marrow transplants without causing serious side effects. Tested in both humans and animals, this imaging method has not been linked to harmful reactions.

Similarly, researchers have studied TK1 blood measurements, another part of this study, for their potential to predict transplant success. However, less detailed safety information is available specifically for TK1. Since this trial is in an early phase, the main focus is on checking safety and collecting initial data. Researchers closely monitor the treatment for any side effects. Overall, both methods are considered safe based on existing research, but ongoing trials will provide more information. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores innovative methods for detecting graft failure early in patients undergoing hematopoietic stem cell transplantation (HSCT). Unlike traditional methods that rely on clinical signs and blood tests, this trial uses FLT PET/CT imaging to visualize cellular activity in the body, potentially identifying graft issues much earlier. Additionally, TK1 blood measurements offer a novel biochemical approach to monitor cell proliferation, providing another layer of insight into the patient's engraftment status. These techniques could lead to more timely interventions, improving outcomes for patients undergoing HSCT.

What evidence suggests that FLT imaging and TK1 blood measurements are effective for detecting graft failure?

Research has shown that FLT imaging, one of the methods studied in this trial, can help identify issues with bone marrow transplants. Participants in the "Cord and haplo imaging cohort" will undergo FLT PET/CT imaging at specified intervals to detect differences in patients who might experience complications like graft-versus-host disease after a transplant. This imaging method identifies early signs of graft failure, allowing for quicker treatment decisions. Meanwhile, the "Nonengrafted cohort" will have a single FLT PET/CT image to determine if this scan can identify graft failure versus delayed engraftment. Early evidence suggests that using FLT imaging, along with blood tests for TK1, might help doctors assess whether new bone marrow cells are growing properly. This could lead to better outcomes by addressing problems sooner. ^{1 2 3 5 6}

Who Is on the Research Team?

Kirsten M Williams, MD

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

This trial is for patients aged 4-70 at high risk of graft failure after bone marrow transplant, such as those with cord blood HSCT or haplo HSCT. Participants must not have had investigational therapies in the last 28 days and should be in remission before HSCT. Pregnant individuals, those with certain allergies, active malignancies outside the hematopoietic system, significant systemic illness, or psychiatric disorders affecting compliance are excluded.

Inclusion Criteria

Patient or guardian able to give informed consent

No investigational therapies within past 28 days

For Arm A: Absence of donor specific antibodies to cord HLA for cord blood recipients, ≥ 5/10 and < 7/8 allele mismatch donor for haplo-identical recipients, diagnosed with a condition for which myeloablative 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, FEV1 > 80% pre or post-bronchiolator whichever is higher, DLCO Adj > 70%, Sa02 > 94% on room air, ejection fraction > 50%

Exclusion Criteria

I cannot or will not use birth control during the study.

I have chosen not to participate in the CIBMTR research study.

Pregnant or lactating females

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Transplant Imaging

FLT PET/CT imaging occurs one day prior to hematopoietic stem cell transplantation (HSCT)

1 day

1 visit (in-person)

Post-Transplant Monitoring

FLT imaging and blood biomarker analysis to monitor engraftment on days 9 and 28 after HSCT

28 days

3 visits (in-person)

Nonengraftment Evaluation

For patients not engrafted by day 24, a single FLT PET/CT image is taken within one week to assess graft failure versus delayed engraftment

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• FLT imaging
• TK1 blood measurements

Trial Overview The study is testing FLT imaging and TK1 blood measurements to see if they can help determine how well new bone marrow cells are growing post-transplantation. It's looking for better tests to decide if a patient's newly infused bone marrow cells are engrafting successfully or if another transplant might be needed.

How Is the Trial Designed?

Group I: Nonengrafted cohort Experimental Treatment 1 Intervention

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.

Group II: Cord and haplo imaging cohort Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

University of Oklahoma

Lead Sponsor

Trials

484

Recruited

95,900+

University Hospitals Cleveland Medical Center

Collaborator

Trials

348

Recruited

394,000+

University Hospital of Cleveland

Collaborator

Trials

1

Recruited

60+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

University of Michigan

Collaborator

Trials

1,891

Recruited

6,458,000+

Emory University

Collaborator

Trials

1,735

Recruited

2,605,000+

Published Research Related to This Trial

Combining advanced imaging techniques like MSCT with PET or scintigraphy enhances the ability to assess blood flow and tissue viability in patients with atherosclerosis, which can improve diagnosis and treatment decisions.

MSCT alone has already significantly transformed cardiology practices by providing accurate and clear imaging for calcium scoring and coronary angiography, making it a valuable tool for screening high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Positron emission and computed tomographies in cardiology. Toussaint, JF.[2016]

Early graft patency is crucial for reducing complications after coronary artery bypass surgery, with surgical errors contributing to early graft failure, particularly within the first year.

Transit time flowmetry (TTFM) is the most widely used method for intraoperative graft evaluation, yet only about 20% of North American cardiac surgeons utilize it; combining TTFM with high-resolution epicardial ultrasonography enhances diagnostic accuracy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Techniques for intraoperative graft assessment in coronary artery bypass surgery. Ohmes, LB., Di Franco, A., Di Giammarco, G., et al.[2020]

In a study of 15 heart transplant patients, 13N-ammonia PET imaging demonstrated excellent correlation with cardiovascular magnetic resonance (CMR) imaging for measuring myocardial strain, indicating its effectiveness in assessing cardiac function post-transplant.

The study found high reproducibility in strain measurements from PET, with intraclass correlation coefficients of 0.89 for circumferential strain and 0.85 for longitudinal strain, suggesting that PET can be a reliable tool for detecting cardiac allograft vasculopathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

13N-ammonia positron emission tomography-derived left-ventricular strain in patients after heart transplantation validated using cardiovascular magnetic resonance feature tracking as reference. Kawakubo, M., Nagao, M., Kikuchi, N., et al.[2022]

In a study of 152 patients suspected of having vascular graft and endograft infection (VGEI), the use of 18F-fluoro-D-deoxyglucose positron emission tomography with low dose CT ([18F]FDG-PET/LDCT) demonstrated high sensitivity (91%) but lower specificity (72%) for diagnosing VGEI.

Less than half of the [18F]FDG-PET/LDCT reports met all pre-selected reporting criteria, and reports that were incomplete showed significantly lower sensitivity and specificity, highlighting the need for standardized reporting guidelines to improve diagnostic accuracy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Variability of [18F]FDG-PET/LDCT reporting in vascular graft and endograft infection. Liesker, DJ., Legtenberg, S., Erba, PA., et al.[2023]

18F-fluorodeoxyglucose (FDG) PET or PET/CT demonstrated a high sensitivity of 96% for detecting vascular prosthetic graft infections (VPGI) across 10 studies involving 286 patients, indicating it is very effective at identifying these infections.

The specificity was moderate at 74%, suggesting that while the test is good at detecting infections, there may be some false positives, and further large multicenter studies are needed to confirm its clinical usefulness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review and meta-analysis of 18F-fluorodeoxyglucose positron emission tomography or positron emission tomography/computed tomography for detection of infected prosthetic vascular grafts. Kim, SJ., Lee, SW., Jeong, SY., et al.[2020]

A study involving 60 kidney transplant patients demonstrated that low-dose three-dimensional MR renography can effectively differentiate between causes of acute graft dysfunction, such as acute rejection and acute tubular necrosis (ATN).

Significant differences in glomerular filtration rate (GFR) and mean transit time (MTT) were observed between patients with normal kidney function and those with acute dysfunction, indicating that this imaging technique provides valuable insights into kidney health post-transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative evaluation of acute renal transplant dysfunction with low-dose three-dimensional MR renography. Yamamoto, A., Zhang, JL., Rusinek, H., et al.[2021]

White blood cell imaging using isotopes like 111In or 99mTc-HMPAO is a sensitive and specific method for detecting vascular graft infections, particularly effective for perioperative or low-grade infections compared to conventional imaging techniques.

The study highlights three case reports where isotopic imaging successfully confirmed the diagnosis of vascular graft infection, underscoring its utility in challenging diagnostic situations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[How I explore ... value of isotopic techniques in the detection of sepsis in valvular prostheses]. Karsera, D., Belhocine, TZ., Foidart-Willems, J., et al.[2016]

Advancements in imaging technologies, such as cardiovascular magnetic resonance and computed tomography, have significantly improved the ability to monitor heart health and graft function after cardiac transplantation, enhancing patient survival rates.

This review highlights the strengths and weaknesses of various imaging techniques, emphasizing their roles in assessing tissue composition and myocardial metabolism, which are crucial for effective graft surveillance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging imaging techniques after cardiac transplantation. McDiarmid, AK., Plein, S., Ross, HJ.[2018]

In a study involving 13 dogs with Dacron aortic grafts, Indium-111-labeled leukocyte imaging demonstrated a sensitivity of 71%, specificity of 100%, and overall accuracy of 85% in detecting early vascular graft infections.

The study found that false-positive results were not an issue in the early postoperative period, suggesting that leukocyte scanning could be a reliable diagnostic tool for identifying graft infections clinically.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of acute synthetic vascular graft infection with 111In-labeled leukocyte scanning: an animal study. Dries, DJ., Alazraki, N., Lawrence, PF., et al.[2016]

The study evaluated 95 kidney transplant recipients using 18F-FDG PET/CT imaging to assess kidney allograft rejection, demonstrating high repeatability and reproducibility in measuring renal 18F-FDG uptake.

Intra-class correlation coefficients (ICC) showed excellent consistency for intra-observer measurements (0.96) and good inter-observer reproducibility (ranging from 0.83 to 0.87), indicating that this imaging technique can reliably be used in clinical practice to evaluate kidney transplant health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Observer variability in the assessment of renal 18F-FDG uptake in kidney transplant recipients. Jadoul, A., Lovinfosse, P., Bouquegneau, A., et al.[2021]

In a pilot study involving 7 patients with multiligament reconstructed knees, fluorodeoxyglucose positron emission tomography (PET) combined with CT successfully detected increased metabolic activity in replacement grafts during the first two years post-surgery.

The imaging technique showed significantly higher fluorodeoxyglucose uptake in the operated knees compared to the non-operated side, indicating its potential as an effective method for assessing graft viability and metabolism, although further research with larger groups is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tendon Graft Healing in Multiligament Reconstructed Knee Detected by FDG-PET/CT: A Pilot Study. Itälä, A., Alihanka, S., Kosola, J., et al.[2017]

The study evaluated the use of rapamycin-treated 18F-FDG-labeled splenocytes for imaging skin allografts in mice, revealing that rapamycin significantly impaired the migration of these cells to the graft site, which could affect imaging efficacy.

In vivo imaging showed that allografts receiving untreated splenocytes (FC cells) had significantly higher radioactivity compared to those receiving rapamycin-treated splenocytes (FR cells), indicating that rapamycin may hinder the effectiveness of this imaging strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti‑migratory effect of rapamycin impairs allograft imaging by 18F‑fluorodeoxyglucose‑labeled splenocytes. Sun, H., Cheng, D., Ma, Y., et al.[2017]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11791676/

18F-FLT PET and Blood-based Biomarkers for Identifying ... Ultrasonographic evaluation of gastrointestinal graft-versus-host disease after hematopoietic stem cell transplantation . Clin Transplant 2015.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03546556

18-FLT PET/MR Imaging to Predict Graft Failure and GVHD ... The current proposal explores the use of a novel imaging modality, FLT PET/MRI, to correlate allogeneic transplant outcomes with FLT and MRI findings during ...

3. reporter.nih.gov reporter.nih.gov/project-details/10482333

Imaging and Blood Biomarkers to Predict Graft Failure after ... If confirmed, FLT and TK1 could be used to identify primary graft failure early after HSCT, permitting expeditious rescue HSCT and significantly improved ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S235230262030003X

Imaging haemopoietic stem cells and microenvironment ... This Viewpoint summarises the data regarding the use of nuclear medicine techniques to assess the phases of HSCT: pre-transplant homoeostasis, induced aplasia, ...

5. astctjournal.org astctjournal.org/article/S1083-8791(18)30381-1/fulltext

18F-3′-Deoxy-3′-Fluorothymidine Positron Emission ... Here we report that FLT PET imaging can differentiate mice receiving alloreactive T cells and destined to develop lethal aGVHD from control mice.

6. sciencedirect.com sciencedirect.com/science/article/am/pii/S2352302617302156

Imaging of subclinical haemopoiesis after stem-cell ... We aimed to determine whether imaging with 18F-fluorothymidine (FLT) was safe during HSCT, could visualize early cellular proliferation and detect a pattern of ...