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Imaging Studies and the Development of Multiple Myeloma

This study has been withdrawn prior to enrollment.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01571726
First Posted: April 5, 2012
Last Update Posted: July 7, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
  Purpose

Background:

- Multiple myeloma (MM) is a type of malignant blood cancer. It affects the plasma cells, which help produce antibodies and fight infection. MM is nearly always preceded by a pre-malignant state, monoclonal gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma (SMM). Currently, it is not possible to predict when someone with MGUS or SMM will develop MM. Also, the disease changes in those early states are not well understood. Researchers want to look at imaging studies of people with MGUS, SMM, and MM. They will study whether the growth of blood vessels can be used to predict disease progression.

Objectives:

- To use imaging studies to evaluate disease progression in multiple myeloma.

Eligibility:

- Individuals at least 18 years of age who have MGUS, SMM, or newly diagnosed MM.

Design:

  • Participants will be screened with a physical exam and medical history. They will also have blood and urine tests, and provide bone marrow samples.
  • Participants will have positron emission tomography (PET) scans with the new contrast agent [18]F-Fluciclatide. The contrast agent is intended to show patterns of increased vessel growth in the bone marrow.
  • Participants will also have a magnetic resonance imaging (MRI) scan. This scan will be done according to standard procedures.
  • Researchers will compare these scans with blood tests and other clinical information to study disease progression of MGUS, SMM, and MM....

Condition Intervention Phase
Multiple Myeloma Smoldering Multiple Myeloma Monoclonal Gammopathy of Undetermined Significance Drug: Fluciclatide Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Novel Imaging Modalities to Characterize Angiogenesis in the Bone Marrow Microenvironment in Multiple Myeloma (MM) and Its Precursor Disease

Resource links provided by NLM:


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

Primary Outcome Measures:
  • To explore the distribution of 18F-Fluciclatide PET/CT in bone marrow microenvironment in patients with multiple myeloma and its precursor disease (MGUS and SMM) [ Time Frame: 1 year ]

Secondary Outcome Measures:
  • Distribution of agent [ Time Frame: 2 years ]

Enrollment: 0
Study Start Date: March 27, 2012
Study Completion Date: April 23, 2014
Primary Completion Date: April 23, 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Fluciclatide
    7mCi
  Hide Detailed Description

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 3,000 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, and the biological changes occurring in those precursor states remain poorly understood.
  • Angiogenesis is a hallmark of multiple myeloma and its precursor disease.

Angiogenesis has been measured using microvessel density. In a prior study, we have demonstrated increased microvessel density using CD34 immunohistochemistry in patients with multiple myeloma, compared to SMM or MGUS, suggesting that there is increased vascular density as the disease progresses. A correlation between MM disease stage and prognosis has been reported for several serum angiogenic factors and myeloma cells and bone marrow endothelial cells have been shown to secrete and respond to angiogenic modulators.

  • Dynamic contrast-enhanced (DCE)-MRI is a noninvasive way to evaluate angiogenesis. In a prior NIH study, we have demonstrated that the kep (a measure of contrast influx in vessels in the bone marrow microenvironment) to be gradually higher in MM>SMM>MGUS, however it was limited to imaging a single field of view (i.e. the lumbar spine). This is also highly correlated with microvessel density.
  • Fluciclatide is a small cyclic peptide containing the RGD tri-peptide, which preferentially binds with high affinity to Alpha(v)Beta(3) integrins, which are up-regulated in angiogenesis.
  • Alpha(v)Beta(3) integrins are also expressed on certain types of tumor cells and on activiated osteoclasts.
  • (18)Fluciclatide (previously known (18)F-AH111585) is a new radiopharmaceutical developed for PET imaging, which targets Alpha(v)Beta(3) receptors.
  • Novel imaging modalities using tracers specific for angiogenesis, using (18)F-Fluciclatide whole-body PET/CT imaging may improve our ability to predict patients who are at high risk of progression.

Objectives:

  • The primary objective of the study is to explore the distribution of (18)F-Fluciclatide PET/CT in bone marrow microenvironment in patients with multiple myeloma and its precursor disease.
  • The secondary objectives are to preliminarily evaluate the distribution of (18)Fluciclatide PET/CT with respect to DCE-MRI and bone marrow vascularity determined by immunohistochemistry (CD34) on the bone marrow biopsy specimen.
  • To preliminarily evaluate the distribution of (18)F-Fluciclatide PET/CT with respect to 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.
  • Subjects with frank multiple myeloma will be enrolled first. If the (18)F-Fluciclatide PET/CT is negative in the first 5 subjects, the study will be aborted and we will not proceed with MGUS or SMM patients. However if the 18F-Fluciclatide PET/CT is positive in MM patients, then we will proceed with MGUS and SMM patients.
  • Subsequently (18)F-Fluciclatide PET/CT and DCE-MRI imaging will be done in all the patients. When feasible, an optional non-contrast wholebody MR may also be performed.
  • 10 MM, 10 SMM and 10 MGUS patients will be enrolled on this protocol.
  • Patients may donate cellular products or tissues as appropriate for research purposes.
  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 99 Years   (Adult, Senior)
Sexes Eligible for Study:   All
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. The diagnosis will be confirmed by the following diagnostic tests:

    • serum/urine protein electrophoresis
    • serum/urine immunofixation,
    • light-chain assays,
    • a skeletal survey, or
  • immunohistochemistry analyses of the bone marrow biopsy, or
  • a combination of these at the NIH

Note: Written results from institutions outside of NIH for the above tests will be accepted if available.

  • 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.
  • Platelet count = or > 100,000. Subjects must weight <320lbs
  • Creatinine <2.5 times ULN or eGFR>30 ml/min/1.73m(2)

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 3 years.
  • Patients with documented metastatic lesions from another type of malignancy will be excluded.
  • Female subject is pregnant or breast-feeding.
  • The subject has known allergy to gadolinium
  • The subject has contraindications to MRI

    • Subjects must weigh <136 kg (weight limit for scanner table).
    • Subjects cannot have pacemakers, cerebral aneurysm clips, shrapnel injury, or other implanted electronic devices or metal not compatible with MRI.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01571726


Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Carl O Landgren, M.D. National Cancer Institute (NCI)
  More Information

Publications:
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01571726     History of Changes
Other Study ID Numbers: 120106
12-C-0106
First Submitted: April 4, 2012
First Posted: April 5, 2012
Last Update Posted: July 7, 2017
Last Verified: April 16, 2014

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
(18)-Fluciclatide PET/CT
Serum M-Protein
Percentage of Plasma Cells in the Bone Marrow
Ratio of Normal/Abnormal Percentage of Plasma Cells in the Bone Marrow
Multiple Myeloma

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