Graft Vs Host DiseaseEarly Phase 1NCT03546556
18-FLT PET/MR Imaging to Predict Graft Failure and GVHD in Bone Marrow Transplant Patients
A Early Phase 1 study testing Fluorothymidine (FLT) in people with Graft Vs Host Disease, run by UNC Lineberger Comprehensive Cancer Center at 1 site in United States.
Trial summary
Allogeneic HSCT is potentially curative for numerous high risk hematologic malignancies and offers several advantages over traditional chemotherapy. First, higher doses of cytotoxic chemotherapy and/or irradiation can be given since patients are subsequently rescued from the severe myelosuppression induced by the… Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Graft Vs Host Disease
- What is being tested?
- Fluorothymidine (FLT)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jan 2017to 12 Mar 2020
- Phase
- Early Phase 1
- 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 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients undergoing allogeneic bone marrow transplant for acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or myelodysplastic syndrome
- Allogeneic transplant patients receiving either a fully myeloablative or reduced intensity chemotherapy +/- total body irradiation (TBI) conditioning regimen are eligible.
- Allogeneic transplant patients receiving stem cells from a matched related, matched unrelated, mismatched unrelated, mismatched related (including haplotype matched) donors are eligible
- Allogeneic transplant patients must be in a complete morphologic remission prior to transplant
- Patients undergoing autologous bone marrow transplant for multiple myeloma
- Myeloma patients must have achieved at least a very good partial remission prior to transplant and exhibit fewer than 10% plasma cells in their pre-transplant marrow biopsy
- At least 18 years of age
- Negative urine pregnancy test in women of child-bearing potential
Who cannot join
- Any woman who is pregnant or has reason to believe she is pregnant or any woman who is lactating.
- Condition that makes MRI unsafe (e.g., cardiac pacemaker, epicardial pacemaker leads, cochlear implants, metal aneurysm clip, metal halo devices)
- Inability to tolerate MRI (e.g., unable to lie flat for > 1 hour, severe claustrophobia)
- Known allergy to fluorothymidine
- Creatinine clearance < 40 ml/min, as estimated by the Cockcroft-Gault formula
- Body Mass Index (BMI) > 35
Show all 10Show fewer
- Poorly controlled diabetes mellitus (fasting blood glucose > 500 mg/dl)
- Institutionalized subject (prisoner or nursing home patient)
- Critically ill or medically unstable
- Currently hospitalized (All FLT PET/MR scans will be obtained in the outpatient setting)
Trial locations and contacts
1 site in 1 country.
United States1 site
Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
About this study
Official title: 18-FLT PET/MR Imaging to Predict Graft Failure and Graft Versus Host Disease in Bone Marrow Transplant Patients
Allogeneic HSCT is potentially curative for numerous high risk hematologic malignancies and offers several advantages over traditional chemotherapy. First, higher doses of cytotoxic chemotherapy and/or irradiation can be given since patients are subsequently rescued from the severe myelosuppression induced by the pre-transplant conditioning regimen by the infusion of healthy hematopoietic stem cells.
Second and perhaps more importantly, mature T cells contained in the graft are able to mount immune responses against residual cancer cells surviving the conditioning regimen due to major and/or minor MHC disparities between the donor and recipient. Unfortunately, the allo-immune responses driving the GVL effect are typically not specific for malignant cells. As a consequence, donor immune cells attack normal host tissues resulting in a process known as acute graft-versus-host disease (GVHD). Acute GVHD is primarily T cell driven, usually occurs within the first few months after transplant, and results in skin rash, diarrhea, cholestatic liver damage, and, on occasion, acute lung injury.
Read the detailed description
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 early stem cell engraftment and at a later time point following stable count recovery. Specifically, this study will determine if the strength of the early FLT signal within the bone marrow correlates with engraftment success and if isolated areas of cellular proliferation within the marrow at a later time point might predict for leukemia relapse. In addition, based on the important role that host lymphoid tissues are known to play in GVHD pathogenesis in mice, this study will determine if the FLT signal within host SLT after transplant can predict for the development of GVHD in human BMT patients. Because FLT imaging by itself cannot distinguish between bone marrow engraftment/proliferation and the allo-immune driven T cell expansion that ultimately results in GVHD, this study will image autologous transplant patients as a comparator arm. Autologous HSCT like allogeneic transplantation involves the administration of very high doses of chemotherapy to high risk cancer patients in order to achieve better tumor kill. However, in this situation patients are administered their own cryopreserved stem cells to reconstitute the ablated hematopoietic system. Under those circumstances there is no allo-immune reactivity to drive T cell activation and expansion after transplant, and as a result there is no GVHD in the autologous transplant setting. Thus, these patients will help us to elucidate how much of the FLT signal seen in the allogeneic setting is the result of allo-immune driven T cell expansion.
- Conditions
- Graft Vs Host Disease
- Being tested
- Fluorothymidine (FLT)
- Medical subject headings
- Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fluorothymidine (FLT)Drug
Also called 18F-FLT, 3'-deoxy-3'-(18F) fluorothymidine, 3'-deoxy-3'-[18F]fluorothymidine, fluorothymidine F 18
A total of 12 patients who have undergone allogenic bone marrow transplantation will undergo FLT-PET-MRI imaging on two separate occasions. In addition to the 12 allogenic transplant patients, 3 patients undergoing autologous stem cell transplant will also be imaged the same two time points in order to determine how much of the FLT signal observed after allogeneic transplant is unique to that population and the result of allo-antigen driven T cell expansion.
| Study group | Role | What they receive |
|---|---|---|
| Allogeneic | Experimental | A total of 12 patients who have undergone allogenic bone marrow transplantation will undergo Fluorothymidine FLT-PET-MRI imaging on two separate occasions. Receives: Drug: Fluorothymidine (FLT) |
| Autologous | Experimental | 3 patients undergoing autologous stem cell transplant will also undergo Fluorothymidine FLT-PET-MRI imaging the same two time points in order to determine how much of the FLT signal observed after allogeneic transplant is unique to that population and the result of allo-antigen driven T cell expansion. Receives: Drug: Fluorothymidine (FLT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall FLT-PET Bone Marrow Signal
Compare the overall FLT-PET bone marrow signal on transplant day +25 between allogeneic stem cell transplant recipients who do and do not go on to achieve complete donor bone marrow reconstitution by transplant day +35.
Measured: 35 Days (Approximate)
Overall FLT-PET Signal Intensity within Host Secondary Lymphoid Sites
Compare the overall FLT-PET signal intensity within host secondary lymphoid sites on transplant day +60 between allogeneic stem cell transplant recipients who do and do not develop acute GVHD by transplant day +100.
Measured: 100 Days (Approximate)
Secondary outcomes (10)
Overall Long-Term FLT-PET Bone Marrow Signal
Compare the overall FLT-PET bone marrow signal on transplant day +60 between allogeneic stem cell transplant recipients who do and do not achieve complete donor bone marrow reconstitution by transplant day +100.
Measured: 100 Days (Approximate)
Overall Long-Term FLT-PET Signal Intensity within Host Secondary Lymphoid Sites
Compare the overall FLT-PET signal intensity within host secondary lymphoid sites on transplant day +25 between allogeneic stem cell transplant recipients who do and do not develop acute GVHD by transplant day +100.
Measured: 100 Days (Approximate)
Differences in FLT Uptake in Autologous HSCT and Allogeneic HSCT Patients
Evaluate differences in FLT uptake within the bone marrow and secondary lymphoid tissues in patients undergoing autologous hematopoietic stem cell transplantation (HSCT) versus allogeneic HSCT.
Measured: 100 Days (Approximate)
Strength of FLT-PET Signal and Transfusion Independence
Correlate the strength of the FLT-PET signal within the bone marrow on transplant day +25 with the rate of transfusion independence on transplant day +35 in allogeneic stem cell transplant recipients.
Measured: 35 Days (Approximate)
Strength of the FLT-PET Signal and Bone Marrow Cellularity
Correlate the strength of the FLT-PET signal within the bone marrow on transplant day +25 with bone marrow cellularity on transplant day +35 in allogeneic stem cell transplant recipients.
Measured: 35 Days (Approximate)
Strength of FLT-PET Signal and Transfusion Independence (Long Term)
Correlate the strength of the FLT-PET signal within the bone marrow on transplant day +60 with the rate of transfusion independence on transplant day +100 in allogeneic stem cell transplant recipients.
Measured: 100 Days (Approximate)
Strength of FLT-PET Signal and Bone Marrow Cellularity (Long Term)
Correlate the strength of the FLT-PET signal within the bone marrow on transplant day +60 with bone marrow cellularity on transplant day +100 in allogeneic stem cell transplant recipients.
Measured: 100 Days (Approximate)
Isolated/Asymmetric Foci of Increased FLT
Evaluate if isolated or asymmetric foci of increased FLT within the bone marrow or lymph nodes on transplant day +60 are associated with the incidence of disease relapse by day +100 in allogeneic stem cell transplant recipients.
Measured: 100 Days (Approximate)
Strength of FLT-PET signal and MRI Findings
Correlate the strength of the FLT-PET signal within the bone marrow on transplant day +25 and on day +60 with MRI findings suggestive of engraftment in allogeneic stem cell transplant recipients.
Measured: 60 Days (Approximate)
Overall FLT-PET Signal Intensity and Acute Graft Versus Host Disease
Evaluate the association of the overall FLT-PET signal intensity within host secondary lymphoid sites on transplant day +60 with the overall incidence of acute graft versus host disease and malignancy relapse over the first transplant year.
Measured: 60 Days (Approximate)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2018
- Study start1 Jan 2017
- Primary completion12 Mar 2020
- Study completion12 Mar 2020
Why it stopped: Study terminated due to COVID-19 pandemic and not being able to perform PET/MR scans on participants.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Graft Vs Host DiseaseStudies of the same condition, open and under way.
- More trials run by UNC Lineberger Comprehensive Cancer CenterThe 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
- Early Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- UNC Lineberger Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Z Lee, MD/PhD, Principal investigator, University of North Carolina, Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03546556
- Sponsor's protocol ID
- LCCC 1714
- Status last verified
- Dec 2024
- First submitted
- 19 Mar 2018
- Last updated
- 10 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 10 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 18-FLT PET/MR Imaging to Predict Graft Failure and Graft Versus Host Disease in Bone Marrow Transplant Patients
- ClinicalTrials.gov ID
- NCT03546556
- Acronym / sponsor ID
- LCCC 1714
- Conditions
- Graft Vs Host Disease
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study terminated due to COVID-19 pandemic and not being able to perform PET/MR scans on participants.
- Enrolment
- 10 participants (actual)
- Lead sponsor
- UNC Lineberger Comprehensive Cancer CenterUniversity, hospital or other
- Study start
- 1 Jan 2017 (actual)
- Primary completion
- 12 Mar 2020 (actual)
- Study completion
- 12 Mar 2020 (actual)
- First posted
- 6 Jun 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.
Allogeneic HSCT is potentially curative for numerous high risk hematologic malignancies and offers several advantages over traditional chemotherapy. First, higher doses of cytotoxic chemotherapy and/or irradiation can be given since patients are subsequently rescued from the severe myelosuppression induced by the pre-transplant conditioning regimen by the infusion of healthy hematopoietic stem cells.
Second and perhaps more importantly, mature T cells contained in the graft are able to mount immune responses against residual cancer cells surviving the conditioning regimen due to major and/or minor MHC disparities between the donor and recipient. Unfortunately, the allo-immune responses driving the GVL effect are typically not specific for malignant cells. As a consequence, donor immune cells attack normal host tissues resulting in a process known as acute graft-versus-host disease (GVHD). Acute GVHD is primarily T cell driven, usually occurs within the first few months after transplant, and results in skin rash, diarrhea, cholestatic liver damage, and, on occasion, acute lung injury.
Detailed description
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 early stem cell engraftment and at a later time point following stable count recovery. Specifically, this study will determine if the strength of the early FLT signal within the bone marrow correlates with engraftment success and if isolated areas of cellular proliferation within the marrow at a later time point might predict for leukemia relapse. In addition, based on the important role that host lymphoid tissues are known to play in GVHD pathogenesis in mice, this study will determine if the FLT signal within host SLT after transplant can predict for the development of GVHD in human BMT patients. Because FLT imaging by itself cannot distinguish between bone marrow engraftment/proliferation and the allo-immune driven T cell expansion that ultimately results in GVHD, this study will image autologous transplant patients as a comparator arm. Autologous HSCT like allogeneic transplantation involves the administration of very high doses of chemotherapy to high risk cancer patients in order to achieve better tumor kill. However, in this situation patients are administered their own cryopreserved stem cells to reconstitute the ablated hematopoietic system. Under those circumstances there is no allo-immune reactivity to drive T cell activation and expansion after transplant, and as a result there is no GVHD in the autologous transplant setting. Thus, these patients will help us to elucidate how much of the FLT signal seen in the allogeneic setting is the result of allo-immune driven T cell expansion.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Allogeneic | Experimental | Drug: Fluorothymidine (FLT)A total of 12 patients who have undergone allogenic bone marrow transplantation will undergo Fluorothymidine FLT-PET-MRI imaging on two separate occasions. |
| Autologous | Experimental | Drug: Fluorothymidine (FLT)3 patients undergoing autologous stem cell transplant will also undergo Fluorothymidine FLT-PET-MRI imaging the same two time points in order to determine how much of the FLT signal observed after allogeneic transplant is unique to that population and the result of allo-antigen driven T cell expansion. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients undergoing allogeneic bone marrow transplant for acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or myelodysplastic syndrome
- Allogeneic transplant patients receiving either a fully myeloablative or reduced intensity chemotherapy +/- total body irradiation (TBI) conditioning regimen are eligible.
- Allogeneic transplant patients receiving stem cells from a matched related, matched unrelated, mismatched unrelated, mismatched related (including haplotype matched) donors are eligible
- Allogeneic transplant patients must be in a complete morphologic remission prior to transplant
- Patients undergoing autologous bone marrow transplant for multiple myeloma
Key exclusion criteria (10 listed)
- Any woman who is pregnant or has reason to believe she is pregnant or any woman who is lactating.
- Condition that makes MRI unsafe (e.g., cardiac pacemaker, epicardial pacemaker leads, cochlear implants, metal aneurysm clip, metal halo devices)
- Inability to tolerate MRI (e.g., unable to lie flat for > 1 hour, severe claustrophobia)
- Known allergy to fluorothymidine
- Creatinine clearance < 40 ml/min, as estimated by the Cockcroft-Gault formula
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 |
|---|---|---|
| Fluorothymidine (FLT)Also: 18F-FLT, 3'-deoxy-3'-(18F) fluorothymidine, 3'-deoxy-3'-[18F]fluorothymidine, fluorothymidine F 18A total of 12 patients who have undergone allogenic bone marrow transplantation will undergo FLT-PET-MRI imaging on two separate occasions. In addition to the 12 allogenic transplant patients, 3 patients undergoing autologous stem cell transplant will also be imaged the same two time points in order to determine how much of the FLT signal observed after allogeneic transplant is unique to that population and the result of allo-antigen driven T cell expansion. | Drug | Allogeneic, Autologous |
Primary outcome
Overall FLT-PET Bone Marrow Signal
Time frame: 35 Days (Approximate)
Compare the overall FLT-PET bone marrow signal on transplant day +25 between allogeneic stem cell transplant recipients who do and do not go on to achieve complete donor bone marrow reconstitution by transplant day +35.
Overall FLT-PET Signal Intensity within Host Secondary Lymphoid Sites
Time frame: 100 Days (Approximate)
Compare the overall FLT-PET signal intensity within host secondary lymphoid sites on transplant day +60 between allogeneic stem cell transplant recipients who do and do not develop acute GVHD by transplant day +100.
10 secondary outcomes
Overall Long-Term FLT-PET Bone Marrow Signal
Time frame: 100 Days (Approximate)
Overall Long-Term FLT-PET Signal Intensity within Host Secondary Lymphoid Sites
Time frame: 100 Days (Approximate)
Differences in FLT Uptake in Autologous HSCT and Allogeneic HSCT Patients
Time frame: 100 Days (Approximate)
Strength of FLT-PET Signal and Transfusion Independence
Time frame: 35 Days (Approximate)
Strength of the FLT-PET Signal and Bone Marrow Cellularity
Time frame: 35 Days (Approximate)
Strength of FLT-PET Signal and Transfusion Independence (Long Term)
Time frame: 100 Days (Approximate)
Strength of FLT-PET Signal and Bone Marrow Cellularity (Long Term)
Time frame: 100 Days (Approximate)
Isolated/Asymmetric Foci of Increased FLT
Time frame: 100 Days (Approximate)
Strength of FLT-PET signal and MRI Findings
Time frame: 60 Days (Approximate)
Overall FLT-PET Signal Intensity and Acute Graft Versus Host Disease
Time frame: 60 Days (Approximate)
Results and safety
The study was stopped early (reason given: Study terminated due to COVID-19 pandemic and not being able to perform PET/MR scans on participants.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Dec 2024.
- UNC Lineberger Comprehensive Cancer Center Clinical TrialsLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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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.
Z Lee, MD/PhD principal investigator
University of North Carolina, Chapel Hill
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Fluorothymidine (FLT) in people with Graft Vs Host Disease, run by UNC Lineberger Comprehensive Cancer Center at 1 site 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 8 inclusion and 10 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: stopped early, as of the sponsor's last update on 10 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Study terminated due to COVID-19 pandemic and not being able to perform PET/MR scans on participants.). Results are not available in the source record.
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?
Overall FLT-PET Bone Marrow Signal (time frame: 35 Days (Approximate)). The study lists 2 primary outcomes in all. 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 10 Dec 2024; AzTrials last refreshed its copy on 7 Nov 2026.