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

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Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
No phase specifiedBiomarker/Laboratory analysis, Natural history/EpidemiologyCompleted18 and overNCI100096
10-C-0096, NCT01109407

Trial Description



  • Multiple myeloma is a type of cancer that affects white blood cells and has a poor long-term survival rate. Two other types of cancer, monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma (SMM), may eventually progress and develop into multiple myeloma. Researchers are interested in collecting samples from individuals who have been diagnosed with MGUS and SMM to study possible risk factors for developing multiple myeloma.


  • To study risk factors that may cause MGUS and SMM to progress to multiple myeloma.


  • Individuals at least 18 years of age who have been diagnosed with either MGUS or SMM but do not have multiple myeloma.


  • Participants will be examined by study researchers at the initial visit, at 6 months following enrollment, and every 12 months for a maximum of 5 years.
  • The following tests may be performed: (1) blood and urine tests, (2) bone marrow aspiration and biopsy, (3) imaging studies, and (4) a skeletal survey (a series of skeletal X-rays of the skull, spine, pelvis, ribs, shoulders, upper arm, and thigh bones).
  • Treatment will not be provided as part of this protocol. - Participants will remain on the study for 5 years, or until their MGUS or SMM progresses to multiple myeloma requiring treatment.

Further Study Information


  • Multiple Myeloma (MM) is an incurable 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.
  • Current risk stratification schemes rely on serum protein markers and phenotyping by flow cytometry. While they can differentiate high and low risk patients, they cannot predict outcome for individual patients, are not integrated with one another, and have limited direct correlation to biology.
  • Paired samples linked to clinical information can advance research into improved risk stratification, the pathogenesis of MGUS, SMM, and MM, and the potential for an early treatment window for these incurable diseases.


  • To characterize the natural history and prognosis of MGUS and SMM
  • To integrate protein markers (including immunoglobulin free light-chains) and immunophenotyping by flow cytometry with molecular profiles (including gene expression profiles) and clinical outcomes
  • To apply expertise and diagnostic technology to provide improved evaluation, monitoring, and risk-stratification for patients on this protocol
  • To provide paired samples of blood and tissue linked to clinical and molecular information for pilot translational studies


  • A confirmed diagnosis of MGUS or SMM (based on IMWG diagnostic criteria)
  • Age greater than or equal to 18 years
  • ECOG performance status in the range of 0-2
  • Patients who have a diagnosis of MM are not eligible for this study.


  • This is a prospective cohort study of patients with either MGUS or SMM.
  • Following initial evaluation and confirmation of diagnosis, patients will be followed as clinically indicated, usually at 12 month intervals.
  • The primary endpoint is progression to MM requiring treatment.
  • Patients may donate cellular products or tissues as appropriate for research purposes.

154 patients with MGUS and 154 patients with SMM will be enrolled on this protocol.

Eligibility Criteria

  • Diagnosis of MGUS and SMM will be made in accordance with the clinical diagnostic criteria set forth by the International Myeloma Working Group (Table 1).
  • The diagnoses will be confirmed by either serum/urine protein electrophoresis, immunofixation and light-chain assays; or immunohistochemistry analyses of the bone marrow biopsy, or a combination of these tests.
  • 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.


  • A diagnosis of MM as defined as any patient with detectable M-protein in blood and/or urine, monoclonal plasma cells in the bone marrow, and evidence of end-organ damage (based on the International Myeloma Working Group s diagnostic CRAB criteria:

hypercalcemia [serum calcium at least 1 mg/dL above the upper limit of normal], renal failure [creatinine greater than 1.95 mg/dL), anemia (hemoglobin less than 10 g/dL], or bone lesions [lytic lesions or osteoporosis with compression fractures]).

  • Patients who have received previous therapy for MM.

Trial Contact Information

Trial Lead Organizations/Sponsors

National Cancer Institute

    Mark J Roschewski, M.D., Principal Investigator

    Link to the current record.
    NLM Identifier NCT01109407 processed this data on April 09, 2015

    Note: Information about this trial is from the database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the record to standardize the names of study sponsors, sites, and contacts. only lists sites that are recruiting patients for active trials, whereas lists all sites for all trials. Questions and comments regarding the presented information should be directed to