Clinical trial NCT01237054
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
Sponsor: National Cancer Institute (NCI)
Start date: 2010-10-17; Completion date: 2011-08-09
Enrollment: 31 participants; Allocation: NA; Intervention model: SINGLE_GROUP

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).

Arms: arm 1: 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).
Interventions: intervention 1: 18-NaF PET intervention 2: DCE-MRI intervention 3: 18-FDG PET/CT
Intervention descriptions: intervention 1: 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. intervention 2: 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). intervention 3: 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.

Protocol documents: