Clinical trial NCT01237054: Imaging in MGUS, SMM and MM
Official title: A Pilot Study of Novel Imaging Modalities in Monoclonal Gammopathy of Undetermined Significance (MGUS), Smoldering Multiple Myeloma (SMM), and Multiple Myeloma (MM)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2010-11-09
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

Detailed description: Background:

* Multiple myeloma (MM) is a plasma cell neoplasm with a median survival of 3-4 years.
* Monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma (SMM) are premalignant plasma cell proliferative disorders characterized by elevated monoclonal protein and bone marrow plasma cells. MGUS affects 3.2% of Caucasians over the age of 50 and has a 1% annual risk of progression to MM.

Approximately 3000 cases of SMM are diagnosed annually with a 10% annual risk of progression to MM.

* Currently, it is not possible to predict which patients will progress to MM.
* Novel imaging modalities (FDG-PET, 18-NaF PET and DCE-MRI) may improve our ability to predict patients who are at high risk of progression.

Objectives:

* To compare the results of imaging modalities (18-NaF PET/CT, 18-FDG PET/CT, and DCE-MRI) in patients with MGUS, SMM, and MM.
* To correlate the imaging studies with established clinical markers of progression from MGUS/SMM to MM, including serum M-protein, percentage of plasma cells in the bone marrow, serum free light-chain abnormalities and immunoparesis, and ratio of normal/abnormal plasma cells in the bone marrow by flow cytometry.

Eligibility:

* A confirmed diagnosis of MGUS, SMM or MM (based on IMWG (International Myeloma Working Group) diagnostic criteria)
* Age greater than or equal to 18 years
* ECOG (Eastern Cooperative Oncology Group) performance status in the range of 0-2

Design:

* This is a cross-sectional pilot study of patients with MGUS, SMM or MM.
* Following initial evaluation and confirmation of diagnosis, baseline studies including skeletal survey will be done.
* Subsequently 18-NaF PET/CT, 18-FDG PET/CT and DCE-MRI imaging will be done in all the patients.
* 10 MGUS, 11 SMM and 10 MM patients will be enrolled on this protocol.
* Patients may donate cellular products or tissues as appropriate for research purposes.
* Almost all MGUS and SMM patients will be followed clinically as part of 10-C-0096:

Natural History Study of Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Myeloma (SMM).

Eligibility criteria: * INCLUSION CRITERIA:
* 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

EXCLUSION CRITERIA:

* 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.

Primary outcomes:
measure: 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.
timeFrame: 60 days
measure: Count of Participants With Positive DCE-MRI Imaging Results
timeFrame: 60 days
Secondary outcomes:
measure: 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
timeFrame: 60 days
measure: Comparison of Microvessel Density (MVD) Among Patients With MGUS, SMM, and MM
timeFrame: 60 days
measure: Comparison of Reverse Contrast Transfer Rate (Kep) and Forward Contrast Transfer Rate (Ktrans) Among Patients With MGUS, SMM, and MM
timeFrame: 60 days
measure: Comparison of Serum Angiogenic Marker Reverse Contrast Transfer Rate (Kep) Between MGUS and SMM/MM Groups
timeFrame: 60 days
measure: Comparison of Microvessel Density (MVD) Between MGUS and SMM/MM Groups
timeFrame: 60 days
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center, 9000 Rockville Pike
state: Maryland
Study officials:
affiliation: National Cancer Institute (NCI)
name: Peter L Choyke, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.