<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02187731</url>
  </required_header>
  <id_info>
    <org_study_id>S-20120209</org_study_id>
    <secondary_id>13/24748</secondary_id>
    <nct_id>NCT02187731</nct_id>
  </id_info>
  <brief_title>Functional Imaging in Multiple Myeloma -PET/CT and Diffusion Weighted Imaging in Multiple Myeloma</brief_title>
  <acronym>FULIMA</acronym>
  <official_title>FULIMA - A Prospective Study of Dual Time PET/CT and Diffusion Weighted MRI in Multiple Myeloma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Odense University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Odense University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The FULIMA study is a two-center study at Odense University Hospital and Vejle Hospital,&#xD;
      Denmark. The primary objective is to identify the optimal imaging technique for studies in&#xD;
      multiple myeloma with focus on PET/CT and MRI.&#xD;
&#xD;
      By combining early (1 hour) and late (3 hours) 18F-2-fluoro-2-deoxy-D-&#xD;
      fluorodeoxyglucose(18F-FDG)-PET/CT scans the investigators expect to see increased uptake of&#xD;
      radioactive tracer and thus an improved ability to identify malignant tissue. A second tracer&#xD;
      18F-natrium-fluoride is used to explore early signs of bone remodeling. By using new software&#xD;
      (ROVER) for interpreting PET data the investigators expect to obtain a quantitative&#xD;
      measurement of total disease burden with less risk of misinterpretation of data.&#xD;
&#xD;
      Diffusion weighted MRI (DWI) is a new MRI technique which, like PET/CT, makes it possible&#xD;
      quantitatively to calculate the overall disease activity and to give an early evaluation of&#xD;
      response to chemotherapy. The study examines DWI for development and standardization.&#xD;
&#xD;
      To validate imaging findings and to explore the pathogenetic heterogeneity of multiple&#xD;
      myeloma, the investigators perform CT guided biopsies from PET/ DWI positive sites.&#xD;
      Pathoanatomical and immunohistochemical findings and gene expression data from positive sites&#xD;
      are compared to random bone marrow. The question is whether disease heterogeneity may explain&#xD;
      the lack of FDG uptake in bone marrow in some patients? To the extent that the FULIMA study&#xD;
      produces useful data, the defined and standardized imaging techniques will form the basis of&#xD;
      a larger prospective study at national level in Denmark.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">June 2013</start_date>
  <completion_date type="Anticipated">December 2020</completion_date>
  <primary_completion_date type="Anticipated">December 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Multiple myeloma identified as bone disease, myeloma or plasmacytoma</measure>
    <time_frame>&quot;baseline&quot;</time_frame>
    <description>A 1st complete set of imaging procedures is completed at time of diagnosis &quot;baseline&quot; (week 1-2) for all patients included in the study. The primary hypothesis that 3-hour FDG-PET / CT finds more malignant lesions than the current gold standard procedure, whole body x-ray(WBXR), together with CT and MRI. Concordance analysis will be done by summarizing comparisons of 3-hours FDG-PET/CT versus the remaining modalities. We measure a 95% Wilson-Score Confidence Interval (CI) to demonstrate that 3hours FDG-PET / CT find more malignant lesions than gold standard. This will be concluded at a significance level of 5% if the lower boundary of the 95% CI is larger than 30%.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Disease heterogeneity</measure>
    <time_frame>Within 2 weeks after imaging procedures</time_frame>
    <description>CT guided or Ultra Sound guided biopsies from PET/ DWI positive sites. Pathoanatomical and immunohistochemical findings and gene expression data from positive sites are compared to random bone marrow.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Early signs of bone remodeling</measure>
    <time_frame>&quot;baseline&quot;, after induction treatment and after end of treatment</time_frame>
    <description>18F-natrium-fluoride-PET/CT is performed at time of diagnosis (baseline) during week 1-2, after induction treatment and after end of treatment. We test if increased 18F-natrium-fluoride uptake is seen in bone sites where, according to CT and DWI, no abnormal bone remodeling is taking place and we observe the association between FDG-PET and fluoride-PET and markers of bone metabolism. We use descriptive statistics for number of bone sites with increased fluoride uptake, 95% Confidence interval</description>
  </secondary_outcome>
  <enrollment type="Actual">70</enrollment>
  <condition>Multiple Myeloma</condition>
  <eligibility>
    <study_pop>
      <textblock>
        Prospective study with 60 patients referred to Haematological Department under the&#xD;
        suspicion of having treatment demanding multiple myeloma. Patients will be included from&#xD;
        two centres of Haematology.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female subjects &gt; 50 years at time of signing informed consent.&#xD;
&#xD;
          2. Subject under suspicion of having treatment demanding multiple myeloma in concordance&#xD;
             with Danish cancer package criteria&#xD;
&#xD;
          3. Signed informed consent before performance of any study related procedures.&#xD;
&#xD;
          4. Subject is willing and able to comply with the protocol as judged by the investigator.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Formerly treated multiple myeloma.&#xD;
&#xD;
          2. Known inflammatory disease, recent biological therapies or chemotherapy for&#xD;
             non-malignant disease (less than 3 months prior to screening), clinically relevant&#xD;
             active infection.&#xD;
&#xD;
          3. Concurrent or recent radiotherapy or surgery less than two weeks prior to screening&#xD;
&#xD;
          4. Glucocorticoid treatment exceeding 10 mg Prednisolone daily, less than two weeks prior&#xD;
             to screening.&#xD;
&#xD;
          5. Any condition, including laboratory abnormalities, that in the opinion of the&#xD;
             investigator places the subject at an unacceptable risk if s/he were to participate in&#xD;
             the study, e.g. high levels of liver-enzymes and creatinine.&#xD;
&#xD;
          6. Female subject is pregnant or breast feeding.&#xD;
&#xD;
          7. Serious co-morbidity, and other medical or psychiatric illness likely to interfere&#xD;
             with participation in this clinical study.&#xD;
&#xD;
          8. Uncontrolled diabetes at the discretion of the investigator.&#xD;
&#xD;
          9. Known or prior malignancy except for adequately treated basal cell or squamous cell&#xD;
             skin cancer, in situ cervical cancer, in situ breast cancer or in situ prostate cancer&#xD;
             for which the subject has been disease free for at least three years.&#xD;
&#xD;
         10. POEMS syndrome (plasma cell dyscrasia with poly-neuropathy, organomegaly,&#xD;
             endocrinopathy, monoclonal protein (M-protein) and skin changes).&#xD;
&#xD;
         11. Exclusion according to MRI procedure (metal implants, claustrophobia, pace-maker).&#xD;
&#xD;
         12. Exclusion according to biopsy study (thrombocytes &lt; 50x /L, activated partial&#xD;
             thromboplastin time(APTT) &gt; 40 sec, and international normalized ratio(INR) &gt; 1.5)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Brian Oestergaard, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Odense University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Odense University Hospital</name>
      <address>
        <city>Odense C</city>
        <zip>5000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>April 23, 2014</study_first_submitted>
  <study_first_submitted_qc>July 10, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 11, 2014</study_first_posted>
  <last_update_submitted>August 28, 2018</last_update_submitted>
  <last_update_submitted_qc>August 28, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 29, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Odense University Hospital</investigator_affiliation>
    <investigator_full_name>Brian Oestergaard</investigator_full_name>
    <investigator_title>MD</investigator_title>
  </responsible_party>
  <keyword>Multiple Myeloma</keyword>
  <keyword>Functional Imaging</keyword>
  <keyword>PET/CT</keyword>
  <keyword>Diffusion Weighted MRI</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Myeloma</mesh_term>
    <mesh_term>Neoplasms, Plasma Cell</mesh_term>
    <mesh_term>Body Weight</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02187731
org study id: S-20120209
secondary id: 13/24748
nct id: NCT02187731
lead sponsor: 
has dmc: Yes
The FULIMA study is a two-center study at Odense University Hospital and Vejle Hospital,
      Denmark. The primary objective is to identify the optimal imaging technique for studies in
      multiple myeloma with focus on PET/CT and MRI.

      By combining early (1 hour) and late (3 hours) 18F-2-fluoro-2-deoxy-D-
      fluorodeoxyglucose(18F-FDG)-PET/CT scans the investigators expect to see increased uptake of
      radioactive tracer and thus an improved ability to identify malignant tissue. A second tracer
      18F-natrium-fluoride is used to explore early signs of bone remodeling. By using new software
      (ROVER) for interpreting PET data the investigators expect to obtain a quantitative
      measurement of total disease burden with less risk of misinterpretation of data.

      Diffusion weighted MRI (DWI) is a new MRI technique which, like PET/CT, makes it possible
      quantitatively to calculate the overall disease activity and to give an early evaluation of
      response to chemotherapy. The study examines DWI for development and standardization.

      To validate imaging findings and to explore the pathogenetic heterogeneity of multiple
      myeloma, the investigators perform CT guided biopsies from PET/ DWI positive sites.
      Pathoanatomical and immunohistochemical findings and gene expression data from positive sites
      are compared to random bone marrow. The question is whether disease heterogeneity may explain
      the lack of FDG uptake in bone marrow in some patients? To the extent that the FULIMA study
      produces useful data, the defined and standardized imaging techniques will form the basis of
      a larger prospective study at national level in Denmark.
observational model: Other
time perspective: Prospective
measure: Multiple myeloma identified as bone disease, myeloma or plasmacytoma
time frame: "baseline"
description: A 1st complete set of imaging procedures is completed at time of diagnosis "baseline" (week 1-2) for all patients included in the study. The primary hypothesis that 3-hour FDG-PET / CT finds more malignant lesions than the current gold standard procedure, whole body x-ray(WBXR), together with CT and MRI. Concordance analysis will be done by summarizing comparisons of 3-hours FDG-PET/CT versus the remaining modalities. We measure a 95% Wilson-Score Confidence Interval (CI) to demonstrate that 3hours FDG-PET / CT find more malignant lesions than gold standard. This will be concluded at a significance level of 5% if the lower boundary of the 95% CI is larger than 30%.
measure: Disease heterogeneity
time frame: Within 2 weeks after imaging procedures
description: CT guided or Ultra Sound guided biopsies from PET/ DWI positive sites. Pathoanatomical and immunohistochemical findings and gene expression data from positive sites are compared to random bone marrow.
measure: Early signs of bone remodeling
time frame: "baseline", after induction treatment and after end of treatment
description: 18F-natrium-fluoride-PET/CT is performed at time of diagnosis (baseline) during week 1-2, after induction treatment and after end of treatment. We test if increased 18F-natrium-fluoride uptake is seen in bone sites where, according to CT and DWI, no abnormal bone remodeling is taking place and we observe the association between FDG-PET and fluoride-PET and markers of bone metabolism. We use descriptive statistics for number of bone sites with increased fluoride uptake, 95% Confidence interval
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 50 Years
maximum age: N/A
healthy volunteers: No
last name: Brian Oestergaard, MD
role: Principal Investigator
affiliation: Odense University Hospital
facility: 
country: Denmark
responsible party type: Principal Investigator
investigator affiliation: Odense University Hospital
investigator full name: Brian Oestergaard
investigator title: MD
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Body Weight