Imaging in MGUS, SMM and MM

Multiple Myeloma Clinical Trial

Official title:

A Pilot Study of Novel Imaging Modalities in Monoclonal Gammopathy of Undetermined Significance (MGUS), Smoldering Multiple Myeloma (SMM), and Multiple Myeloma (MM)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01237054
• Other study ID #: 110020
• Secondary ID: 11-C-0020
• Status: Completed
• Phase: Phase 2
• First received: November 6, 2010
• Last updated: October 5, 2015
• Start date: October 2010
• Est. completion date: August 2011

Study information

• Verified date: October 2015
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: August 2011
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

• 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.

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Monoclonal Gammopathy of Undetermined Significance
• Multiple Myeloma
• Neoplasms, Plasma Cell
• Paraproteinemias
• Smoldering Multiple Myeloma

Intervention

Drug:
• 18-NaF PET
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.

Other:
• DCE-MRI
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).

Drug:
• 18-FDG PET/CT
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.

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. — View Citation

Kristinsson SY, Landgren O, Dickman PW, Derolf AR, Björkholm 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. Epub 2007 Apr 9. — View 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. Epub 2007 Nov 1. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number 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	No
Primary	Number 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	No