Graft Versus Host Disease
Conditions
Keywords
PET-CT scan, [18F]F-AraG
Brief summary
This is a single-center imaging study to determine utility of in vivo imaging with \[18F\]F-AraG to identify sites of Graft Versus Host Disease (GVHD) in patients highly suspected of having acute GVHD who require systemic therapy, and patients at high risk for developing acute GVHD. \[18F\]F-AraG PET scans will be compared to biopsy results to correlate T cell accumulation which is implicated in the disease. High risk patients will be followed to verify predictive potential of \[18F\]F-AraG.
Detailed description
This single-center imaging study will enroll three cohorts of participants: healthy volunteers, patients highly suspected to have acute GVHD (aGVHD) and requiring systemic therapy, and patients at high risk for developing GVHD. A total of 5 healthy volunteers will undergo \[18F\]F-AraG PET scans and blood sampling to better understand \[18F\]F-AraG biodistribution and stability in the body. A total of 10 highly suspected acute GVHD patients will be scanned following biopsy taken to confirm aGVHD. The staging and grading of the disease using the Glucksberg grade and International Bone Marrow Transplant Registry Severity Index (IBMTR) at time of enrollment will be noted. Biopsy tissues of consented patients will be analyzed further for T cell involvement. A total of 15 high-risk patients (recipients of myeloablative or reduced intensity allogeneic transplants using either bone marrow or peripheral blood stem cells from HLA-matched or HLA-mismatched related or unrelated donors-protocols 9142, 9022, 9924) will be recruited. All those that consent will undergo a PET-CT scan with \[18F\]FAraG on day 4 +/- 2 days post transplant. Additionally, these patients will be scanned again between day 14-21 post transplant. Follow up on these patients will note those that go on to develop aGVHD and the clinical end point will be correlated to the scans to verify the predictive potential of the radiotracer.
Interventions
DRUG[18F]F-Ara-G
the \[18F\]F-AraG tracer will be administered as a single bolus injection of approximately 5 mCi into a hand or arm vein.
Sponsors
Stanford University
National Cancer Institute (NCI)
CellSight Technologies, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Must be 21 years of age or older. 2. Must understand and voluntarily have signed an Informed Consent after its contents have been fully explained. 1. For patients highly suspected to have aGVHD and requiring systemic therapy, informed consent should be signed after biopsy taken to support clinical diagnosis. 2. For patients at high risk for developing aGVHD, informed consent should be signed prior to transplant. 3. For healthy volunteers only: Must have no known medical problems that would make undergoing the scan hazardous to the health of the patient or interfere with the results. In particular subjects should not have any cardiac or immunological disorders as these would likely affect the scan results. Subjects should have had a full physical exam within 6 months of the study. If healthy volunteers have not had a full medical exam within 6 months of the study, one of the nuclear medicine physicians will conduct the medical exam prior to any study procedures. 4. For patients highly suspected to have aGVHD and requiring systemic therapy only: Taking steroid treatment for suspected aGVHD for 3 days or less. 5. For patients at high risk for developing aGVHD only: Recipients of myeloablative or reduced intensity allogeneic transplants using either bone marrow or peripheral blood stem cells from HLA-matched or HLA-mismatched related or unrelated donors (protocols 9142, 9022, 9924) who have not yet been placed on any therapy for acute GVHD.
Exclusion criteria
1. Pregnant or nursing 2. Individuals with known or suspected substance abuse, obtained by self-reporting. 3. Uncontrolled infection 4. Relapsed/persistent malignancy 5. Currently receiving immunotherapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Distribution of Acute GVHD Grades (MAGIC Criteria) at Time of PET/CT Scan | At the time of the PET/CT scan: within 7 days of GVHD suspicion for the Highly Suspected arm, and at the Day 4 ± 2 post-transplant scan for the High-Risk arm | Acute GVHD severity was graded using the Mount Sinai Acute GVHD International Consortium (MAGIC) criteria (Grades I-IV). Grades were assigned based on organ involvement documented in the clinical chart and biopsy review at the time of the PET/CT scan. We reported the number of participants within each grade. |
| Number of Participants Who Developed aGVHD Within 6 Months Post-Scan. | From PET/CT scan to 6 months post-scan. | All participants were followed for 6 months post-imaging. Development of GVHD was defined by clinical diagnosis documented in the medical record.. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Biodistribution and Kinetic Behavior of [18F]F-AraG in Healthy Volunteers | Follow up will occur 2 to 7 days post scan. | This outcome was intended to assess biodistribution and kinetic behavior of \[18F\]F-AraG in healthy adult volunteers. However, no healthy volunteers were imaged due to funding limitations. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Highly Suspected to Already Have aGVHD Patients highly suspected to have aGVHD. These patients will undergo a \[18F\]F-AraG PET-CT scan following a biopsy taken to confirm aGVHD.
\[18F\]F-Ara-G: the \[18F\]F-AraG tracer will be administered as a single bolus injection of approximately 5 mCi into a hand or arm vein. | 7 |
| High Risk of Developing aGVHD Patients at high risk of developing aGVHD will undergo a \[18F\]F-AraG PET-CT scan on day 4 +/- 2 days post transplant. Additionally these patients will be scanned again between day 14-21 post transplant.
\[18F\]F-Ara-G: the \[18F\]F-AraG tracer will be administered as a single bolus injection of approximately 5 mCi into a hand or arm vein. | 2 |
| Healthy Subjects Healthy subject volunteers will undergo preliminary evaluation to ensure eligibility, receive and sign an informed consent, be enrolled in the trial, and then have a \[18F\]F-AraG PET-CT scan.
\[18F\]F-Ara-G: the \[18F\]F-AraG tracer will be administered as a single bolus injection of approximately 5 mCi into a hand or arm vein. | 0 |
| Total | 9 |
Baseline characteristics
| Characteristic | Highly Suspected to Already Have aGVHD | High Risk of Developing aGVHD | Healthy Subjects | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 2 Participants | 0 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 2 Participants | 0 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 3 Participants | 1 Participants | 0 Participants | 4 Participants |
| Region of Enrollment United States | 7 participants | 2 participants | — | 9 participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 0 Participants | 5 Participants |
| Sex: Female, Male Male | 4 Participants | 0 Participants | 0 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 2 | 0 / 0 |
| other Total, other adverse events | 0 / 7 | 0 / 2 | 0 / 0 |
| serious Total, serious adverse events | 0 / 7 | 0 / 2 | 0 / 0 |
Outcome results
Primary
Distribution of Acute GVHD Grades (MAGIC Criteria) at Time of PET/CT Scan
Acute GVHD severity was graded using the Mount Sinai Acute GVHD International Consortium (MAGIC) criteria (Grades I-IV). Grades were assigned based on organ involvement documented in the clinical chart and biopsy review at the time of the PET/CT scan. We reported the number of participants within each grade.
Time frame: At the time of the PET/CT scan: within 7 days of GVHD suspicion for the Highly Suspected arm, and at the Day 4 ± 2 post-transplant scan for the High-Risk arm
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Highly Suspected to Already Have aGVHD | Distribution of Acute GVHD Grades (MAGIC Criteria) at Time of PET/CT Scan | Grade 3 | 1 Participants |
| Highly Suspected to Already Have aGVHD | Distribution of Acute GVHD Grades (MAGIC Criteria) at Time of PET/CT Scan | Grade 0 | 0 Participants |
| Highly Suspected to Already Have aGVHD | Distribution of Acute GVHD Grades (MAGIC Criteria) at Time of PET/CT Scan | Grade 1 | 0 Participants |
| Highly Suspected to Already Have aGVHD | Distribution of Acute GVHD Grades (MAGIC Criteria) at Time of PET/CT Scan | Grade 2 | 4 Participants |
| Highly Suspected to Already Have aGVHD | Distribution of Acute GVHD Grades (MAGIC Criteria) at Time of PET/CT Scan | Grade 4 | 1 Participants |
| High Risk of Developing aGVHD | Distribution of Acute GVHD Grades (MAGIC Criteria) at Time of PET/CT Scan | Grade 4 | 0 Participants |
| High Risk of Developing aGVHD | Distribution of Acute GVHD Grades (MAGIC Criteria) at Time of PET/CT Scan | Grade 2 | 0 Participants |
| High Risk of Developing aGVHD | Distribution of Acute GVHD Grades (MAGIC Criteria) at Time of PET/CT Scan | Grade 0 | 2 Participants |
| High Risk of Developing aGVHD | Distribution of Acute GVHD Grades (MAGIC Criteria) at Time of PET/CT Scan | Grade 3 | 0 Participants |
| High Risk of Developing aGVHD | Distribution of Acute GVHD Grades (MAGIC Criteria) at Time of PET/CT Scan | Grade 1 | 0 Participants |
Primary
Number of Participants Who Developed aGVHD Within 6 Months Post-Scan.
All participants were followed for 6 months post-imaging. Development of GVHD was defined by clinical diagnosis documented in the medical record..
Time frame: From PET/CT scan to 6 months post-scan.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Highly Suspected to Already Have aGVHD | Number of Participants Who Developed aGVHD Within 6 Months Post-Scan. | 6 Participants |
| High Risk of Developing aGVHD | Number of Participants Who Developed aGVHD Within 6 Months Post-Scan. | 2 Participants |
Secondary
Biodistribution and Kinetic Behavior of [18F]F-AraG in Healthy Volunteers
This outcome was intended to assess biodistribution and kinetic behavior of \[18F\]F-AraG in healthy adult volunteers. However, no healthy volunteers were imaged due to funding limitations.
Time frame: Follow up will occur 2 to 7 days post scan.
Population: No healthy volunteers were imaged due to loss of study funding; therefore, no data were collected for this outcome.