Imaging in MGUS, SMM and MM

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT01237054
First received: November 6, 2010
Last updated: June 14, 2014
Last verified: April 2014
  Purpose

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 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).
  • 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.

Condition Intervention Phase
Multiple Myeloma
Smoldering Multiple Myeloma
Monoclonal Gammopathy of Undetermined Significance
Drug: 18-NaF PET
Other: DCE-MRI
Drug: 18-FDG PET/CT
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: A Pilot Study of Novel Imaging Modalities in Monoclonal Gammopathy of Undetermined Significance (MGUS), Smoldering Multiple Myeloma (SMM), and Multiple Myeloma (MM)

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Compare the results of three imaging techniques in individuals withMGUS, SMM, and MM. [ Time Frame: 60 days ] [ Designated as safety issue: No ]
  • To correlate the imaging studies with established clinical markers ofprogression 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... [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 1.1.2.1 To explore results from the imaging studies in relation to molecular profiles (including gene expression profiling and other biologic and molecular markers) of MM and its precursor states. [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Enrollment: 31
Study Start Date: October 2010
Study Completion Date: August 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
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
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.
Other: 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).
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.

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 diagnostic criteria)
  • Age greater than or equal to 18 years
  • ECOG 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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 performance status of 0-2.
  • The patient must be competent to sign an informed consent form.
  • Creatinine less than 2.5 ULN or eGFR 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01237054

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: Peter L Choyke, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT01237054     History of Changes
Other Study ID Numbers: 110020, 11-C-0020
Study First Received: November 6, 2010
Last Updated: June 14, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
18-FDG PET/CT
Abnormal Plasma Cells
Serum Free Light-Chain Abnormality
Serum M-Protein
DCE-MRI
Multiple Myeloma
Smoldering Multiple Myeloma
SMM
MM

Additional relevant MeSH terms:
Monoclonal Gammopathy of Undetermined Significance
Paraproteinemias
Multiple Myeloma
Neoplasms, Plasma Cell
Hypergammaglobulinemia
Blood Protein Disorders
Hematologic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders

ClinicalTrials.gov processed this record on August 28, 2014