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| ID | Type | Description | Link |
|---|---|---|---|
| 11-C-0020 |
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Background:
- Recent studies have shown that the premalignant conditions monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) have a high risk of progressing to multiple myeloma (MM). There are currently no known effective treatments to prevent MGUS or SMM from developing into MM, and there are no known tests for determining whether an individual with MGUS or SMM will develop MM. Researchers are investigating new and improved imaging techniques that may be able to better detect the progression of MGUS or SMM into MM.
Objectives:
Eligibility:
- Individuals at least 18 years of age who have been diagnosed with monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, or multiple myeloma.
Design:
Background:
Approximately 3000 cases of SMM are diagnosed annually with a 10% annual risk of progression to MM.
Objectives:
Eligibility:
Design:
Natural History Study of Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Myeloma (SMM).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Imaging in MGUS, SMM, and MM | Experimental | 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). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 18-NaF PET | Drug | The patient will receive 5mCi of F-18 NaF IV (intravenous) 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | 60 days |
| Count of Participants With Positive DCE-MRI Imaging Results | 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. | 60 days |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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. |
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EXCLUSION CRITERIA:
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| Name | Affiliation | Role |
|---|---|---|
| Peter L Choyke, M.D. | National Cancer Institute (NCI) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda | Maryland | 20892 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 12780789 | Background | International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol. 2003 Jun;121(5):749-57. | |
| 17420512 | Background | Kristinsson SY, Landgren O, Dickman PW, Derolf AR, Bjorkholm M. Patterns of survival in multiple myeloma: a population-based study of patients diagnosed in Sweden from 1973 to 2003. J Clin Oncol. 2007 May 20;25(15):1993-9. doi: 10.1200/JCO.2006.09.0100. Epub 2007 Apr 9. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | 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. | Posted | Count of Participants | Participants | 60 days |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Peter Choyke | National Cancer Institute | 301-402-8409 | pchoyke@mail.cc.nih.gov |
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| ID | Term |
|---|---|
| D009101 | Multiple Myeloma |
| D000075122 | Smoldering Multiple Myeloma |
| D008998 | Monoclonal Gammopathy of Undetermined Significance |
| ID | Term |
|---|---|
| D054219 | Neoplasms, Plasma Cell |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
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|
| DCE-MRI | Other | An FDA (Food and Drug Administration) 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 | Drug | The 18F-FDG injection procedure will be injected and be followed by a ~20 ml saline (sodium chloride IV infusion 0.9% w/v) flush over a period of ~20 seconds. The injection site will be evaluated pre- and post administration for any reaction (e.g. bleeding, hematoma, redness, or infection). Whole body (vertex to toes) static PET/CT imaging will be performed beginning at 1-hour, and again at 2-hours post injection. |
|
| 60 days |
| Comparison of Microvessel Density (MVD) Among Patients With MGUS, SMM, and MM | 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. | 60 days |
| Comparison of Reverse Contrast Transfer Rate (Kep) and Forward Contrast Transfer Rate (Ktrans) Among Patients With MGUS, SMM, and MM | Pharmacokinetic parameters Kep and Ktrans were measured by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). | 60 days |
| Comparison of Serum Angiogenic Marker Reverse Contrast Transfer Rate (Kep) Between MGUS and SMM/MM Groups | Pharmacokinetic parameter Kep was measured by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). | 60 days |
| Comparison of Microvessel Density (MVD) Between MGUS and SMM/MM Groups | 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). | 60 days |
| 17975015 | Background | Kumar SK, Rajkumar SV, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, Zeldenrust SR, Dingli D, Russell SJ, Lust JA, Greipp PR, Kyle RA, Gertz MA. Improved survival in multiple myeloma and the impact of novel therapies. Blood. 2008 Mar 1;111(5):2516-20. doi: 10.1182/blood-2007-10-116129. Epub 2007 Nov 1. |
| 26690712 | Derived | Bhutani M, Turkbey B, Tan E, Korde N, Kwok M, Manasanch EE, Tageja N, Mailankody S, Roschewski M, Mulquin M, Carpenter A, Lamping E, Minter AR, Weiss BM, Mena E, Lindenberg L, Calvo KR, Maric I, Usmani SZ, Choyke PL, Kurdziel K, Landgren O. Bone marrow abnormalities and early bone lesions in multiple myeloma and its precursor disease: a prospective study using functional and morphologic imaging. Leuk Lymphoma. 2016 May;57(5):1114-21. doi: 10.3109/10428194.2015.1090572. Epub 2016 Apr 7. |
| 24045500 | Derived | Bhutani M, Turkbey B, Tan E, Kemp TJ, Pinto LA, Berg AR, Korde N, Minter AR, Weiss BM, Mena E, Lindenberg L, Aras O, Purdue MP, Hofmann JN, Steinberg SM, Calvo KR, Choyke PL, Maric I, Kurdziel K, Landgren O. Bone marrow angiogenesis in myeloma and its precursor disease: a prospective clinical trial. Leukemia. 2014 Feb;28(2):413-6. doi: 10.1038/leu.2013.268. Epub 2013 Sep 18. No abstract available. |
| years |
|
| Age, Categorical | Count of Participants | Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
Smoldering multiple myeloma (SMM)is a premalignant plasma cell proliferative disorder. |
| OG002 | MM (Multiple Myeloma) | Multiple myeloma is a plasma cell neoplasm. |
|
|
| Primary | Count of Participants With Positive DCE-MRI Imaging Results | 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. | Missing means the imaging test was not done. Unclear means it is indeterminate whether an imaging result is positive or negative. | Posted | Count of Participants | Participants | 60 days |
|
|
|
| Secondary | 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 | 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. | Serum was not available for three patients in the SMM group. | Posted | Mean | Standard Error | pg/ml | 60 days |
|
|
|
|
| Secondary | Comparison of Microvessel Density (MVD) Among Patients With MGUS, SMM, and MM | 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. | Three patients with MM did not undergo bone marrow biopsies and were not included in this analysis. | Posted | Median | Full Range | microvessels/hpf | 60 days |
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| Secondary | Comparison of Reverse Contrast Transfer Rate (Kep) and Forward Contrast Transfer Rate (Ktrans) Among Patients With MGUS, SMM, and MM | Pharmacokinetic parameters Kep and Ktrans were measured by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). | Three patients with MM did not undergo bone marrow biopsies and were not included in this analysis. | Posted | Median | Full Range | per min | 60 days |
|
|
|
|
| Secondary | Comparison of Serum Angiogenic Marker Reverse Contrast Transfer Rate (Kep) Between MGUS and SMM/MM Groups | Pharmacokinetic parameter Kep was measured by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). | Serum was not available for three patients in the SMM group. | Posted | Mean | Standard Error | per min | 60 days |
|
|
|
|
| Secondary | Comparison of Microvessel Density (MVD) Between MGUS and SMM/MM Groups | 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). | Serum was not available for three patients in the SMM group. | Posted | Mean | Standard Error | microvessels/hpf | 60 days |
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|
|
| 0 |
| 31 |
| 0 |
| 31 |
| 0 |
| 31 |
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| D014652 |
| Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D011230 | Precancerous Conditions |
| D006942 | Hypergammaglobulinemia |
| Title | Measurements |
|---|---|
|
| Missing |
|
| Unclear |
|
| Follistatin |
|
| HGF (hepatocyte growth factor) |
|
| VEGF-A (vascular endothelial growth factor-A) |
|
| FGF-1 (fibroblast growth factor 1) |
|
| Endothelin 1 |
|
| 0.055 |
The reported p-value is representative of the difference in levels of G-CSF in both groups. |
| Superiority |
| Wilcoxon rank sum test | 0.055 | The reported p-value is representative of the difference in levels of Follistatin in both groups. | Superiority |
| Wilcoxon rank sum test | 0.0098 | The reported p-value is representative of the difference in levels of HGF in both groups. | Superiority |
| Wilcoxon rank sum test | 0.02 | The reported p-value is representative of the difference in levels of VEGF-A in both groups. | Superiority |
|
| Jonckheere-Terpstra test for trend |
| 0.33 |
The reported p-value is representative of the difference in levels of Ktrans between MGUS and SMM+MM. |
| Other |
Other, trend test. |