Imaging in MGUS, SMM and MM

NCT01237054 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 11002011-C-0020
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

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:

• To compare the results of three imaging techniques in individuals with MGUS, SMM, and MM.
• To correlate the information from the imaging studies with established clinical markers of progression from MGUS/SMM to MM. 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:
• Participants will be screened with a physical examination and medical history, and will provide baseline blood, urine, and bone marrow samples before beginning the imaging studies.
• Participants will have three imaging studies on separate days: a standard 18-fludeoxyglucose 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 dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).
• Participants will be closely monitored during each scan, and will provide additional blood samples before and after the scans.
• Participants may provide additional blood, urine, tissue, and bone marrow samples for optional research studies.

Conditions

Multiple Myeloma; Smoldering Multiple Myeloma; Monoclonal Gammopathy of Undetermined Significance

Keywords

18-FDG PET/CT; Abnormal Plasma Cells; Serum Free Light-Chain Abnormality; Serum M-Protein; DCE-MRI; Multiple Myeloma; Smoldering Multiple Myeloma; SMM; MM

Outcome Measures

Primary Outcomes (2)

• 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

Secondary Outcomes (5)

• 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

  60 days

• Comparison of Microvessel Density (MVD) Among Patients With MGUS, SMM, and MM

  60 days

• Comparison of Reverse Contrast Transfer Rate (Kep) and Forward Contrast Transfer Rate (Ktrans) Among Patients With MGUS, SMM, and MM

  60 days

• Comparison of Serum Angiogenic Marker Reverse Contrast Transfer Rate (Kep) Between MGUS and SMM/MM Groups

  60 days

• Comparison of Microvessel Density (MVD) Between MGUS and SMM/MM Groups

  60 days

Study Arms (1)

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).

Drug: 18-NaF PET; Other: DCE-MRI; Drug: 18-FDG PET/CT

Interventions

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.

Imaging in MGUS, SMM, and MM

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).

Imaging in MGUS, SMM, and MM

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.

Imaging in MGUS, SMM, and MM

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of MGUS, SMM and MM will be made in accordance with the clinical diagnostic criteria set forth by the International Myeloma Working Group.2. The diagnoses will be confirmed by laboratory tests, serum/urine protein electrophoresis, immunofixation and light-chain assays, a skeletal survey, or immunohistochemistry analyses of the bone marrow biopsy, or a combination of these.
• Age greater than or equal to 18 years.
• ECOG (Eastern Cooperative Oncology Group) performance status of 0-2.
• The patient must be competent to sign an informed consent form.
• Creatinine less than 2.5 ULN or eGFR (estimated glomerular filtration rate) greater than 30

You may not qualify if:

• A medical history of other malignancy (apart from basal cell carcinoma of the skin or in situ cervical carcinoma; also, for MM patients this does not include MM) except if the patient has been free of symptoms and without active therapy during at least the previous 5 years.
• Female subject is pregnant or breast-feeding.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (5)

• 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.

  PMID: 12780789 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.

  PMID: 17420512 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.

  PMID: 17975015 BACKGROUND

• 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.

  PMID: 26690712 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.

  PMID: 24045500 DERIVED

MeSH Terms

Conditions

Multiple Myeloma; Smoldering Multiple Myeloma; Monoclonal Gammopathy of Undetermined Significance

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Precancerous Conditions; Hypergammaglobulinemia

Results Point of Contact

• Title: Dr. Peter Choyke
• Organization: National Cancer Institute

pchoyke@mail.cc.nih.gov

301-402-8409

Study Officials

• Peter L Choyke, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 6, 2010
• First Posted: November 9, 2010
• Study Start: October 17, 2010
• Primary Completion: August 9, 2011
• Study Completion: August 9, 2011
• Last Updated: February 6, 2026
• Results First Posted: January 16, 2015

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)