Bone Cancer, Chondrosarcoma, Ewing's Sarcoma, Osteosarcoma, Rhabdomyosarcoma, Bone Necrosis, Bone Sarcoma, Osteomyelitis
Conditions
Brief summary
This pilot trial studies the differentiation of bone sarcomas and osteomyelitis with ferumoxytol-enhanced magnetic resonance imaging (MRI). Imaging procedures that allow doctors to more accurately differentiate between malignant bone sarcomas and osteomyelitis may help in diagnosing patients correctly and may result in more timely treatment.
Detailed description
BACKGROUND; In this study, T1, T2, and T2\* represent parameters of magnetic resonance imaging (MRI). The T1 relaxation time, also known as the spin-lattice relaxation time, is a measure of how quickly the net magnetization vector (NMV) recovers to its ground state in the direction of B0. T1 is assessed immediately post-contrast. A T1-weighted image (T1WI ) is one of the basic pulse sequences in MRI and demonstrates differences in the T1 relaxation times of tissues. A T1WI relies upon the longitudinal relaxation of a tissue's net magnetization vector (NMV). T2 is a time constant for the decay of transverse magnetization arising from natural interactions at the atomic or molecular levels, and be considered the natural or true T2 of the tissue. However, in any nuclear magnetic resonance (NMR) experiment, transverse magnetization decays much faster than would be predicted by natural atomic and molecular mechanisms. Accordingly, T2 \* is the time constant for the decay of transverse magnetization as observed in a tissue during a MRI scan, and be considered theeffective T2 (represented as T2\*). T2\* is always ≤ T2. In this study, T2 \* is assessed after 24 hours. OUTLINE: Patients receive ferumoxytol intravenously (IV) and then undergo ferumoxytol-enhanced MRI up to 1 hour after infusion and up to 24 hours post-infusion. PRIMARY OBJECTIVES: * Establish magnetic resonance (MR) imaging characteristics of bone sarcomas and osteomyelitis based on their ferumoxytol-enhancement on relatively early post-contrast T1-weighted images. * Establish MR imaging characteristics of bone sarcomas and osteomyelitis based on their ferumoxytol-enhancement on delayed postcontrast T2-weighted images. * Establish T2-weighted MR imaging characteristics of iron-labeled mesenchymal stem cell (MSC) in osteonecrotic bone over time, before and after surgical core decompression and bone marrow implantation. * Adding a second branch for patients who can not receive ferumoxytol but still getting the MRI exam. These patients will server as controls.
Interventions
DRUGFeraheme
5 mg/kg by intravenous (IV) administration
Standard of Care magnetic resonance imaging (MRI) scans using GE 1.5T and 3T MRI scanners/
Sponsors
Heike E Daldrup-Link
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
10 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
* Age 10 to 21 years * Suspected or confirmed diagnosis of a bone sarcoma or osteomyelitis * Informed consent with assent as appropriate.
Exclusion criteria
* Contraindication to MRI * Presence of metal implants * Need for sedation or anesthesia * Claustrophobia * Hemosiderosis or hemochromatosis * History of allergic reactions to similar compounds will be obtained and patients with positive history of allergic reactions will be excluded from the study * Females who are pregnancy or nursing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| T2* Relaxation Time of Bone Sarcomas and Osteomyelitis Subjects | 24 hours | Differentiation of bone sarcomas and osteomyelitis with ferumoxytol-enhanced magnetic resonance imaging (MRI) was assessed as the difference of mean T2 \* relaxation time of bone sarcoma and osteomyelitis subjects. The outcome is reported as the difference of the mean T2 \* values, with standard deviation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Differentiation of Bone Sarcomas Pre-ferumoxytol and Post-ferumoxytol Contrast | Baseline and Post-Treatment-24 hours | Differentiation of bone sarcomas pre-ferumoxytol and post-ferumoxytol contrast was assessed by difference of mean T2 \* relaxation time pre-ferumoxytol and post-ferumoxytol contrast, in bone sarcoma subjects only. |
| Differentiation of Lymphoma and Bone Sarcomas With Ferumoxytol-enhanced MRI | 24 hours | Differentiation of lymphoma from bone sarcoma was assessed as the difference of mean T2 \* relaxation time determined by ferumoxytol-enhanced MRI. . |
| Differentiation of CD68-positive Tumor-associated Macrophages (TAM) in Lymphomas and Bone Sarcomas | 24 hours | Differentiation of CD68-positive tumor-associated macrophages (TAM) between lymphoma and bone sarcoma was assessed as the difference of mean area density of CD68-positive TAM in those populations. |
| Differentiation of CD163-positive Tumor-associated Macrophages (TAM) in Lymphomas and Bone Sarcomas | 24 hours | Differentiation of CD163-positive tumor-associated macrophages (TAM) between lymphoma and bone sarcoma was assessed as the difference of mean area density of CD163-positive TAM in those populations. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Feraheme Intravenous injection of Feraheme, 5 mg Fe/kg
Feraheme: 5 mg Fe/kg by intravenous adminstration
MR Scan: Standard of Care | 21 |
| Total | 21 |
Baseline characteristics
| Characteristic | Feraheme |
|---|---|
| Age, Categorical <=18 years | 16 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Age, Continuous | 14.7 Years STANDARD_DEVIATION 4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 19 Participants |
| Region of Enrollment United States | 21 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 21 |
| other Total, other adverse events | 1 / 21 |
| serious Total, serious adverse events | 0 / 21 |
Outcome results
Primary
T2* Relaxation Time of Bone Sarcomas and Osteomyelitis Subjects
Differentiation of bone sarcomas and osteomyelitis with ferumoxytol-enhanced magnetic resonance imaging (MRI) was assessed as the difference of mean T2 \* relaxation time of bone sarcoma and osteomyelitis subjects. The outcome is reported as the difference of the mean T2 \* values, with standard deviation.
Time frame: 24 hours
Population: This initial phase of the study was a pilot assessment of participants with bone sarcomas compared to participants with osteomyelitis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bone Sarcomas | T2* Relaxation Time of Bone Sarcomas and Osteomyelitis Subjects | 7.3 milliseconds | Standard Deviation 1.9 |
| Osteomyelitis | T2* Relaxation Time of Bone Sarcomas and Osteomyelitis Subjects | 7.7 milliseconds | Standard Deviation 1.9 |
Secondary
Differentiation of Bone Sarcomas Pre-ferumoxytol and Post-ferumoxytol Contrast
Differentiation of bone sarcomas pre-ferumoxytol and post-ferumoxytol contrast was assessed by difference of mean T2 \* relaxation time pre-ferumoxytol and post-ferumoxytol contrast, in bone sarcoma subjects only.
Time frame: Baseline and Post-Treatment-24 hours
Population: Only the participants with bone sarcomas were evaluated for this outcome.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bone Sarcomas | Differentiation of Bone Sarcomas Pre-ferumoxytol and Post-ferumoxytol Contrast | Pre-treatment | 13.80 milliseconds | Standard Deviation 2.8 |
| Bone Sarcomas | Differentiation of Bone Sarcomas Pre-ferumoxytol and Post-ferumoxytol Contrast | Post-treatment | 8.27 milliseconds | Standard Deviation 2.12 |
Secondary
Differentiation of CD163-positive Tumor-associated Macrophages (TAM) in Lymphomas and Bone Sarcomas
Differentiation of CD163-positive tumor-associated macrophages (TAM) between lymphoma and bone sarcoma was assessed as the difference of mean area density of CD163-positive TAM in those populations.
Time frame: 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bone Sarcomas | Differentiation of CD163-positive Tumor-associated Macrophages (TAM) in Lymphomas and Bone Sarcomas | 1.9 Percentage area of CD163-positive TAM | Standard Deviation 1.5 |
| Osteomyelitis | Differentiation of CD163-positive Tumor-associated Macrophages (TAM) in Lymphomas and Bone Sarcomas | 9.4 Percentage area of CD163-positive TAM | Standard Deviation 3.1 |
Secondary
Differentiation of CD68-positive Tumor-associated Macrophages (TAM) in Lymphomas and Bone Sarcomas
Differentiation of CD68-positive tumor-associated macrophages (TAM) between lymphoma and bone sarcoma was assessed as the difference of mean area density of CD68-positive TAM in those populations.
Time frame: 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bone Sarcomas | Differentiation of CD68-positive Tumor-associated Macrophages (TAM) in Lymphomas and Bone Sarcomas | 4.8 Percentage of CD68-positive TAM | Standard Deviation 1.2 |
| Osteomyelitis | Differentiation of CD68-positive Tumor-associated Macrophages (TAM) in Lymphomas and Bone Sarcomas | 6.1 Percentage of CD68-positive TAM | Standard Deviation 2.3 |
Secondary
Differentiation of Lymphoma and Bone Sarcomas With Ferumoxytol-enhanced MRI
Differentiation of lymphoma from bone sarcoma was assessed as the difference of mean T2 \* relaxation time determined by ferumoxytol-enhanced MRI. .
Time frame: 24 hours
Population: The analysis population for this outcome includes the participants with bone sarcoma who participated in the pilot study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bone Sarcomas | Differentiation of Lymphoma and Bone Sarcomas With Ferumoxytol-enhanced MRI | 14.83 milliseconds | Standard Deviation 1.03 |
| Osteomyelitis | Differentiation of Lymphoma and Bone Sarcomas With Ferumoxytol-enhanced MRI | 7.71 milliseconds | Standard Deviation 0.6 |