Trial Outcomes & Findings for Imaging in MGUS, SMM and MM (NCT NCT01237054)

NCT ID: NCT01237054

Last Updated: 2026-02-06

Results Overview

18F-FDG PET CT and F18-NaF PET CT imaging results were compared in participants with MGUS, SMM, and MM. Lesions were considered positive if focal uptake corresponded to lesions identified on CT for NaF and negative if no uptake seen in lesions. Criteria to define FDG positivity included parameters published by Zamagni et al with focal abnormal uptake more intense than background.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

31 participants

Primary outcome timeframe

60 days

Results posted on

2026-02-06

Participant Flow

Participant milestones

Participant milestones
Measure
Imaging in MGUS, SMM, and MM
Participants will have three imaging studies on separate days: a standard positron emission tomography/computed tomography scan (18-FDG PET/CT), a PET/CT scan with an experimental sodium fluoride-based drug (18-NaF PET/CT), and magnetic resonance imaging (DCE-MRI). 18-NaF PET: The patient will patient will receive 5mCi of F-18 NaF IV bolus, followed by a \~20 ml saline (sodium chloride IV infusion 0.9% w/v) flush over a period of \~20 seconds. Serial dynamic imaging (2 minutes/bed position) will be obtained over a 1-hour period. The patient will be permitted an imaging break until a static PET/CT is performed beginning at 2-hours post F-18 NaF injection. DCE-MRI: An FDA approved gadolinium chelate (e.g. Magnevist, Berlex Laboratories, NJ, USA) will be administered intravenously at 3 cc/sec using an automated pump injector (Medrad, Pittsburgh, PA, USA).18-FDG PET/CT: The 18F-FDG injection procedure will be injected and be followed by a \~20 ml saline flush over a period of \~20 sec.
Overall Study
STARTED
31
Overall Study
COMPLETED
30
Overall Study
NOT COMPLETED
1

Reasons for withdrawal

Reasons for withdrawal
Measure
Imaging in MGUS, SMM, and MM
Participants will have three imaging studies on separate days: a standard positron emission tomography/computed tomography scan (18-FDG PET/CT), a PET/CT scan with an experimental sodium fluoride-based drug (18-NaF PET/CT), and magnetic resonance imaging (DCE-MRI). 18-NaF PET: The patient will patient will receive 5mCi of F-18 NaF IV bolus, followed by a \~20 ml saline (sodium chloride IV infusion 0.9% w/v) flush over a period of \~20 seconds. Serial dynamic imaging (2 minutes/bed position) will be obtained over a 1-hour period. The patient will be permitted an imaging break until a static PET/CT is performed beginning at 2-hours post F-18 NaF injection. DCE-MRI: An FDA approved gadolinium chelate (e.g. Magnevist, Berlex Laboratories, NJ, USA) will be administered intravenously at 3 cc/sec using an automated pump injector (Medrad, Pittsburgh, PA, USA).18-FDG PET/CT: The 18F-FDG injection procedure will be injected and be followed by a \~20 ml saline flush over a period of \~20 sec.
Overall Study
imaging 10C0096
1

Baseline Characteristics

Imaging in MGUS, SMM and MM

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Imaging in MGUS, SMM, and MM
n=31 Participants
Participants will have three imaging studies on separate days: a standard positron emission tomography/computed tomography scan (18-FDG PET/CT), a PET/CT scan with an experimental sodium fluoride-based drug (18-NaF PET/CT), and magnetic resonance imaging (DCE-MRI). 18-NaF PET: The patient will patient will receive 5mCi of F-18 NaF IV bolus, followed by a \~20 ml saline (sodium chloride IV infusion 0.9% w/v) flush over a period of \~20 seconds. Serial dynamic imaging (2 minutes/bed position) will be obtained over a 1-hour period. The patient will be permitted an imaging break until a static PET/CT is performed beginning at 2-hours post F-18 NaF injection. DCE-MRI: An FDA approved gadolinium chelate (e.g. Magnevist, Berlex Laboratories, NJ, USA) will be administered intravenously at 3 cc/sec using an automated pump injector (Medrad, Pittsburgh, PA, USA).18-FDG PET/CT: The 18F-FDG injection procedure will be injected and be followed by a \~20 ml saline flush over a period of \~20 sec.
Age, Continuous
62.89 years
STANDARD_DEVIATION 10.58 • n=192 Participants
Age, Categorical
<=18 years
0 Participants
n=192 Participants
Age, Categorical
Between 18 and 65 years
20 Participants
n=192 Participants
Age, Categorical
>=65 years
11 Participants
n=192 Participants
Sex: Female, Male
Female
18 Participants
n=192 Participants
Sex: Female, Male
Male
13 Participants
n=192 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=192 Participants
Race (NIH/OMB)
Asian
1 Participants
n=192 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=192 Participants
Race (NIH/OMB)
Black or African American
4 Participants
n=192 Participants
Race (NIH/OMB)
White
26 Participants
n=192 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=192 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=192 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants
n=192 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
31 Participants
n=192 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=192 Participants
Region of Enrollment
United States
31 Participants
n=192 Participants

PRIMARY outcome

Timeframe: 60 days

18F-FDG PET CT and F18-NaF PET CT imaging results were compared in participants with MGUS, SMM, and MM. Lesions were considered positive if focal uptake corresponded to lesions identified on CT for NaF and negative if no uptake seen in lesions. Criteria to define FDG positivity included parameters published by Zamagni et al with focal abnormal uptake more intense than background.

Outcome measures

Outcome measures
Measure
MGUS (Monoclonal Gammopathy of Undetermined Significance)
n=10 Participants
MGUS (Monoclonal gammopathy of undetermined significance) is a premalignant plasma cell proliferative disorder.
SMM (Smoldering Multiple Myeloma)
n=10 Participants
Smoldering multiple myeloma (SMM)is a premalignant plasma cell proliferative disorder.
MM (Multiple Myeloma)
n=10 Participants
Multiple myeloma is a plasma cell neoplasm.
Count of Participants With Positive and Negative 18F-FDG PET CT and F18-NaF PET CT Imaging Results in Individuals With MGUS, SMM, and MM.
Positive F18-NaF PET CT result
0 Participants
0 Participants
9 Participants
Count of Participants With Positive and Negative 18F-FDG PET CT and F18-NaF PET CT Imaging Results in Individuals With MGUS, SMM, and MM.
Positive 18F-FDG PET CT result
0 Participants
1 Participants
5 Participants
Count of Participants With Positive and Negative 18F-FDG PET CT and F18-NaF PET CT Imaging Results in Individuals With MGUS, SMM, and MM.
Negative 18F-FDG PET CT result
10 Participants
9 Participants
5 Participants
Count of Participants With Positive and Negative 18F-FDG PET CT and F18-NaF PET CT Imaging Results in Individuals With MGUS, SMM, and MM.
Negative F18-NaF PET CT result
10 Participants
10 Participants
1 Participants

PRIMARY outcome

Timeframe: 60 days

Population: Missing means the imaging test was not done. Unclear means it is indeterminate whether an imaging result is positive or negative.

DCE-MRI, an FDA approved gadolinium chelate (e.g. Magnevist, Berlex Laboratories, NJ, USA) will be administered intravenously at 3 cc/sec using an automated pump injector (Medrad, Pittsburgh, PA, USA). The criteria was presence of early and diffuse hyper-enhancement compared to the surrounding bone marrow. The pattern of marrow involvement on MRI was characterized as: (1) normal when there was no evidence of abnormal signal intensity; (2) focal, which consisted of localized areas of abnormal marrow; the lesions are darker than yellow marrow and slightly darker than or isointense to red marrow on T1-weights images; (3) diffuse, in which normal bone marrow signal intensity is completely absent, the intervertebral disks appear brighter than or isointense to the diseased marrow; and finally (4) heterogeneous that consists of innumerable small foci of disease on a background of intact marrow, with small dark lesions on T1-weighted images, which become bright on T2-weighted image.

Outcome measures

Outcome measures
Measure
MGUS (Monoclonal Gammopathy of Undetermined Significance)
n=10 Participants
MGUS (Monoclonal gammopathy of undetermined significance) is a premalignant plasma cell proliferative disorder.
SMM (Smoldering Multiple Myeloma)
n=10 Participants
Smoldering multiple myeloma (SMM)is a premalignant plasma cell proliferative disorder.
MM (Multiple Myeloma)
n=10 Participants
Multiple myeloma is a plasma cell neoplasm.
Count of Participants With Positive DCE-MRI Imaging Results
Positive
1 Participants
1 Participants
9 Participants
Count of Participants With Positive DCE-MRI Imaging Results
Negative
9 Participants
9 Participants
0 Participants
Count of Participants With Positive DCE-MRI Imaging Results
Missing
0 Participants
0 Participants
1 Participants
Count of Participants With Positive DCE-MRI Imaging Results
Unclear
0 Participants
0 Participants
0 Participants

SECONDARY outcome

Timeframe: 60 days

Population: Serum was not available for three patients in the SMM group.

The assay was performed according to the manufacture's protocol, and all samples were diluted 1:3. Cytokine values were calculated using a five-parameter standard curve with Bio-Plex Manager 6.1.

Outcome measures

Outcome measures
Measure
MGUS (Monoclonal Gammopathy of Undetermined Significance)
n=10 Participants
MGUS (Monoclonal gammopathy of undetermined significance) is a premalignant plasma cell proliferative disorder.
SMM (Smoldering Multiple Myeloma)
n=17 Participants
Smoldering multiple myeloma (SMM)is a premalignant plasma cell proliferative disorder.
MM (Multiple Myeloma)
Multiple myeloma is a plasma cell neoplasm.
Comparison of Serum Angiogenic Markers Ang2 (Angiopoietin), G-CSF (Granulocyte-colony Stimulating Factor), Follistatin, HGF (Hepatocyte Growth Factor), FGF-1, Endothelin 1, and VEGF-A (Vascular Endothelial Growth Factor-A) Between MGUS and SMM/MM Groups
VEGF-A (vascular endothelial growth factor-A)
844.31 pg/ml
Standard Error 435.94
1301.52 pg/ml
Standard Error 196.47
Comparison of Serum Angiogenic Markers Ang2 (Angiopoietin), G-CSF (Granulocyte-colony Stimulating Factor), Follistatin, HGF (Hepatocyte Growth Factor), FGF-1, Endothelin 1, and VEGF-A (Vascular Endothelial Growth Factor-A) Between MGUS and SMM/MM Groups
Ang2 (angiopoietin)
2465.97 pg/ml
Standard Error 589.27
3804.42 pg/ml
Standard Error 467.16
Comparison of Serum Angiogenic Markers Ang2 (Angiopoietin), G-CSF (Granulocyte-colony Stimulating Factor), Follistatin, HGF (Hepatocyte Growth Factor), FGF-1, Endothelin 1, and VEGF-A (Vascular Endothelial Growth Factor-A) Between MGUS and SMM/MM Groups
G-CSF (granulocyte-colony stimulating factor)
24.92 pg/ml
Standard Error 11.66
101.08 pg/ml
Standard Error 42.81
Comparison of Serum Angiogenic Markers Ang2 (Angiopoietin), G-CSF (Granulocyte-colony Stimulating Factor), Follistatin, HGF (Hepatocyte Growth Factor), FGF-1, Endothelin 1, and VEGF-A (Vascular Endothelial Growth Factor-A) Between MGUS and SMM/MM Groups
Follistatin
562.45 pg/ml
Standard Error 88.89
823.15 pg/ml
Standard Error 83.00
Comparison of Serum Angiogenic Markers Ang2 (Angiopoietin), G-CSF (Granulocyte-colony Stimulating Factor), Follistatin, HGF (Hepatocyte Growth Factor), FGF-1, Endothelin 1, and VEGF-A (Vascular Endothelial Growth Factor-A) Between MGUS and SMM/MM Groups
HGF (hepatocyte growth factor)
390.57 pg/ml
Standard Error 70.82
654.34 pg/ml
Standard Error 57.97
Comparison of Serum Angiogenic Markers Ang2 (Angiopoietin), G-CSF (Granulocyte-colony Stimulating Factor), Follistatin, HGF (Hepatocyte Growth Factor), FGF-1, Endothelin 1, and VEGF-A (Vascular Endothelial Growth Factor-A) Between MGUS and SMM/MM Groups
FGF-1 (fibroblast growth factor 1)
NA pg/ml
Standard Error NA
Serum measures of FGF-1 were below the range of detectability, so these markers were excluded from analysis.
NA pg/ml
Standard Error NA
Serum measures of FGF-1 were below the range of detectability, so these markers were excluded from analysis.
Comparison of Serum Angiogenic Markers Ang2 (Angiopoietin), G-CSF (Granulocyte-colony Stimulating Factor), Follistatin, HGF (Hepatocyte Growth Factor), FGF-1, Endothelin 1, and VEGF-A (Vascular Endothelial Growth Factor-A) Between MGUS and SMM/MM Groups
Endothelin 1
NA pg/ml
Standard Error NA
Serum measures of endothelin-1 were below the range of detectability, so these markers were excluded from analysis.
NA pg/ml
Standard Error NA
Serum measures of endothelin-1 were below the range of detectability, so these markers were excluded from analysis.

SECONDARY outcome

Timeframe: 60 days

Population: Three patients with MM did not undergo bone marrow biopsies and were not included in this analysis.

Microvessel density was estimated by determining the average number of cluster of differentiation 34 (CD34)-stained microvessels in 10 areas of maximal MVD counted at a high-power field (h.p.f. x 500 magnification). Large vessels and vessels in the periosteum on bone were excluded. Areas of staining with no discrete breaks were counted as a single vessel. The presence of a lumen was not required.

Outcome measures

Outcome measures
Measure
MGUS (Monoclonal Gammopathy of Undetermined Significance)
n=10 Participants
MGUS (Monoclonal gammopathy of undetermined significance) is a premalignant plasma cell proliferative disorder.
SMM (Smoldering Multiple Myeloma)
n=10 Participants
Smoldering multiple myeloma (SMM)is a premalignant plasma cell proliferative disorder.
MM (Multiple Myeloma)
n=7 Participants
Multiple myeloma is a plasma cell neoplasm.
Comparison of Microvessel Density (MVD) Among Patients With MGUS, SMM, and MM
15 microvessels/hpf
Interval 15.0 to 19.7
19.4 microvessels/hpf
Interval 7.6 to 32.5
20.9 microvessels/hpf
Interval 10.5 to 37.6

SECONDARY outcome

Timeframe: 60 days

Population: Three patients with MM did not undergo bone marrow biopsies and were not included in this analysis.

Pharmacokinetic parameters Kep and Ktrans were measured by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).

Outcome measures

Outcome measures
Measure
MGUS (Monoclonal Gammopathy of Undetermined Significance)
n=10 Participants
MGUS (Monoclonal gammopathy of undetermined significance) is a premalignant plasma cell proliferative disorder.
SMM (Smoldering Multiple Myeloma)
n=10 Participants
Smoldering multiple myeloma (SMM)is a premalignant plasma cell proliferative disorder.
MM (Multiple Myeloma)
n=7 Participants
Multiple myeloma is a plasma cell neoplasm.
Comparison of Reverse Contrast Transfer Rate (Kep) and Forward Contrast Transfer Rate (Ktrans) Among Patients With MGUS, SMM, and MM
Kep
3.9 per min
Interval 1.6 to 9.2
9 per min
Interval 0.7 to 12.2
5.8 per min
Interval 2.1 to 12.7
Comparison of Reverse Contrast Transfer Rate (Kep) and Forward Contrast Transfer Rate (Ktrans) Among Patients With MGUS, SMM, and MM
Ktrans
2.4 per min
Interval 1.0 to 4.2
2.3 per min
Interval 0.4 to 4.4
3.1 per min
Interval 1.6 to 4.1

SECONDARY outcome

Timeframe: 60 days

Population: Serum was not available for three patients in the SMM group.

Pharmacokinetic parameter Kep was measured by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).

Outcome measures

Outcome measures
Measure
MGUS (Monoclonal Gammopathy of Undetermined Significance)
n=10 Participants
MGUS (Monoclonal gammopathy of undetermined significance) is a premalignant plasma cell proliferative disorder.
SMM (Smoldering Multiple Myeloma)
n=17 Participants
Smoldering multiple myeloma (SMM)is a premalignant plasma cell proliferative disorder.
MM (Multiple Myeloma)
Multiple myeloma is a plasma cell neoplasm.
Comparison of Serum Angiogenic Marker Reverse Contrast Transfer Rate (Kep) Between MGUS and SMM/MM Groups
4.05 per min
Standard Error 0.73
6.93 per min
Standard Error 0.97

SECONDARY outcome

Timeframe: 60 days

Population: Serum was not available for three patients in the SMM group.

Microvessel density was estimated by determining the average number of CD34-stained microvessels in 10 areas of maximal MVD counted at a high-power field (h.p.f. x 500 magnification).

Outcome measures

Outcome measures
Measure
MGUS (Monoclonal Gammopathy of Undetermined Significance)
n=10 Participants
MGUS (Monoclonal gammopathy of undetermined significance) is a premalignant plasma cell proliferative disorder.
SMM (Smoldering Multiple Myeloma)
n=17 Participants
Smoldering multiple myeloma (SMM)is a premalignant plasma cell proliferative disorder.
MM (Multiple Myeloma)
Multiple myeloma is a plasma cell neoplasm.
Comparison of Microvessel Density (MVD) Between MGUS and SMM/MM Groups
15.04 microvessels/hpf
Standard Error 1.14
21.64 microvessels/hpf
Standard Error 1.90

Adverse Events

Imaging in MGUS, SMM, and MM

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Peter Choyke

National Cancer Institute

Phone: 301-402-8409

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place