<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/NCT04493411</url>
  </required_header>
  <id_info>
    <org_study_id>STU-2019-0834</org_study_id>
    <nct_id>NCT04493411</nct_id>
  </id_info>
  <brief_title>Noninvasive Detection and Assessment of Therapy Response in Multiple Myeloma Using Whole-Body MRI</brief_title>
  <official_title>Noninvasive Detection and Assessment of Therapy Response in Multiple Myeloma Using Whole-Body MRI</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Texas Southwestern Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Texas Southwestern Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is designed to prospectively determine the sensitivity, specificity, and&#xD;
      diagnostic accuracy of whole-body MRI (WBMRI) with Dual-Echo T2-weighted acquisition for&#xD;
      Enhanced Conspicuity of Tumors (DETECT) for the detection of multiple myeloma.&#xD;
&#xD;
      Subjects will undergo WBMRI and fluorodeoxyglucose (FDG) positron emission tomography (PET)&#xD;
      for research purposes either at one time point for cross-sectional study or at four time&#xD;
      points for longitudinal study: baseline, prior to bone marrow transplant (BMT), prior to&#xD;
      maintenance therapy, and post BMT. The results of these imaging procedures will be compared&#xD;
      to standard of care whole body x-ray and bone marrow biopsy results.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Whole body magnetic resonance imaging (WBMRI) will be evaluated for detection and assessment&#xD;
      of therapy response in multiple myeloma (MM) using a novel acquisition scheme. WBMRI with&#xD;
      diffusion weighted imaging (DWI) has demonstrated promising preliminary results for detection&#xD;
      and response monitoring in MM. While DWI generates high lesion-to-background contrast and&#xD;
      excellent lesion conspicuity, it suffers from compromised image quality due to geometric&#xD;
      distortion, particularly at 3 Tesla magnetic resonance imaging (MRI), a platform which is&#xD;
      increasingly used in clinical practice. This disadvantage, along with high costs and patient&#xD;
      dissatisfaction associated with long scan times, have limited wide spread adoption of WBMRI&#xD;
      with DWI in the clinical practice.&#xD;
&#xD;
      To overcome these challenges, the investigators have developed an alternative WBMRI&#xD;
      technique: Dual-Echo T2-weighted acquisition for Enhanced Conspicuity of Tumors (DETECT) for&#xD;
      improved tumor visualization by simultaneously suppressing the confounding signals of fat and&#xD;
      fluid throughout the body.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 30, 2020</start_date>
  <completion_date type="Anticipated">September 1, 2026</completion_date>
  <primary_completion_date type="Anticipated">September 1, 2024</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Detection of lesions</measure>
    <time_frame>Up to 4 years</time_frame>
    <description>Effectiveness of WBMRI DETECT for the detection of lesions in MM patients will be compared to WBMRI Diffusion Weighted Imaging (DWI). A combination of clinical MRI, whole body x-ray, FDG PET, and bone marrow biopsy will be used as the reference standard.&#xD;
The number of lesions identified on WBMRI-DETECT will be compared to the number of lesions identified on WBMRI-DWI. The sensitivity and specificity of WBMRI-DETECT and WBMRI-DWI will be calculated using the reference standard.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Assessment of therapy response</measure>
    <time_frame>Up to 4 years</time_frame>
    <description>Effectiveness of WBMRI for assessing therapy response will be compared to the current standard of care using FDG PET and bone marrow biopsy as the validation standard.&#xD;
The percentage increase in fat fraction measured using WBMRI-DETECT and the percentage increase in apparent diffusion coefficient (ADC) measured using WBMRI-DWI will be used to assess the effectiveness of WBMRI in measuring therapy response. The percentage change in SUVmax measured on PET/CT will be used as the reference standard.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Progression Free Survival (PFS)</measure>
    <time_frame>Up to 4 years</time_frame>
    <description>Will determine if WBMRI prognosis is at baseline, after 4-6 weeks of induction therapy, and before maintenance therapy is associated with PFS.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>Up to 4 years</time_frame>
    <description>Will determine if WBMRI prognosis is at baseline, after 4-6 weeks of induction therapy, and before maintenance therapy is associated with OS.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>Multiple Myeloma Patients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with pathologically confirmed myeloma for cross-sectional study (detection) or scheduled to undergo induction therapy (or have gone 1-2 cycles of induction therapy), followed by either bone marrow transplantation or consolidation therapy for longitudinal study (therapy response assessment).</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>WBMRI</intervention_name>
    <description>WBMRI will be performed either at 1 time point for cross-sectional study or at 4 timepoints for the longitudinal study at the following time points.&#xD;
Baseline: (before or after 1-2 cycles of induction therapy)&#xD;
Between Week 12 - 24 (before Bone Marrow Transplant or undergoing consolidation therapy)&#xD;
Between Week 24 - 36 (before starting maintenance therapy)&#xD;
Between Week 60 - 72 (post bone marrow transplant or consolidation therapy and after approximately 9 months of maintenance therapy)</description>
    <arm_group_label>Multiple Myeloma Patients</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Positron Emission Tomography/Computed Tomography (PET/CT)</intervention_name>
    <description>PET/CT will be performed at at 1 time point for cross-sectional study or at 4 timepoints for the longitudinal study at the following time points.&#xD;
Baseline: (before or after 1-2 cycles of induction therapy)&#xD;
Between Week 12 - 24 (before Bone Marrow Transplant or undergoing consolidation therapy)&#xD;
Between Week 24 - 36 (before starting maintenance therapy)&#xD;
Between Week 60 - 72 (post bone marrow transplant or consolidation therapy and after approximately 9 months of maintenance therapy)</description>
    <arm_group_label>Multiple Myeloma Patients</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with pathologically confirmed myeloma.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1, or 2.&#xD;
&#xD;
          -  For cross-sectional study, no additional required treatment schedule. For longitudinal&#xD;
             study: Patients scheduled to undergo bone marrow biopsy (BMB) and induction therapy&#xD;
             (or have gone through 1-2 cycles of induction therapy), followed by either bone marrow&#xD;
             transplantation (BMT) or consolidation therapy.&#xD;
&#xD;
          -  Women of child-bearing potential must agree to undergo a urine pregnancy screening to&#xD;
             prevent imaging of pregnant patients. A female of child-bearing potential is any woman&#xD;
             (regardless of sexual orientation, having undergone a tubal ligation, or remaining&#xD;
             celibate by choice) who meets the following criteria: 1) Has not undergone a&#xD;
             hysterectomy or bilateral oophorectomy; or 2) Has not been naturally postmenopausal&#xD;
             for at least 12 consecutive months (i.e., has had menses at any time in the preceding&#xD;
             12 consecutive months).&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects may not be receiving any other investigational agents for the treatment of&#xD;
             the cancer under study.&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac&#xD;
             arrhythmia, or psychiatric illness/social situations that, in the opinion of the&#xD;
             investigator, would limit compliance with study requirements.&#xD;
&#xD;
          -  Subjects must not be pregnant or nursing; since pregnancy is a contraindication to&#xD;
             administration of gadolinium-based contrast agents. Furthermore, there is a potential&#xD;
             for congenital abnormalities and the potential to harm nursing infants, associated&#xD;
             with FDG-PET.&#xD;
&#xD;
          -  Any contraindication to MRI per Radiology Department's routine protocol, e.g.&#xD;
             MRI-incompatible objects, including but not limited to medical devices and other&#xD;
             foreign bodies.&#xD;
&#xD;
          -  Known severe allergic reaction to Gadolinium-based contrast agents.&#xD;
&#xD;
          -  Patients with uncontrollable claustrophobia, severe lower back pain, and&#xD;
             uncontrollable tremors, to the point that it would render them unable to tolerate an&#xD;
             MRI study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ananth Madhuranthakam, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UT Southwestern Medical Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Kelli Key, PhD</last_name>
    <phone>214-648-8152</phone>
    <email>Kelli.Key@UTSouthwestern.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>UT Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kelli Key, PhD</last_name>
      <phone>214-648-8152</phone>
      <email>Kelli.Key@UTSouthwestern.edu</email>
    </contact>
    <investigator>
      <last_name>Ananth Madhuranthakam, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>July 23, 2020</study_first_submitted>
  <study_first_submitted_qc>July 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 30, 2020</study_first_posted>
  <last_update_submitted>August 29, 2022</last_update_submitted>
  <last_update_submitted_qc>August 29, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 1, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Texas Southwestern Medical Center</investigator_affiliation>
    <investigator_full_name>Ananth Madhuranthakam</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>magnetic resonance imaging</keyword>
  <keyword>positron emission tomography</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>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT04493411
org study id: STU-2019-0834
nct id: NCT04493411
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study is designed to prospectively determine the sensitivity, specificity, and
      diagnostic accuracy of whole-body MRI (WBMRI) with Dual-Echo T2-weighted acquisition for
      Enhanced Conspicuity of Tumors (DETECT) for the detection of multiple myeloma.

      Subjects will undergo WBMRI and fluorodeoxyglucose (FDG) positron emission tomography (PET)
      for research purposes either at one time point for cross-sectional study or at four time
      points for longitudinal study: baseline, prior to bone marrow transplant (BMT), prior to
      maintenance therapy, and post BMT. The results of these imaging procedures will be compared
      to standard of care whole body x-ray and bone marrow biopsy results.
Whole body magnetic resonance imaging (WBMRI) will be evaluated for detection and assessment
      of therapy response in multiple myeloma (MM) using a novel acquisition scheme. WBMRI with
      diffusion weighted imaging (DWI) has demonstrated promising preliminary results for detection
      and response monitoring in MM. While DWI generates high lesion-to-background contrast and
      excellent lesion conspicuity, it suffers from compromised image quality due to geometric
      distortion, particularly at 3 Tesla magnetic resonance imaging (MRI), a platform which is
      increasingly used in clinical practice. This disadvantage, along with high costs and patient
      dissatisfaction associated with long scan times, have limited wide spread adoption of WBMRI
      with DWI in the clinical practice.

      To overcome these challenges, the investigators have developed an alternative WBMRI
      technique: Dual-Echo T2-weighted acquisition for Enhanced Conspicuity of Tumors (DETECT) for
      improved tumor visualization by simultaneously suppressing the confounding signals of fat and
      fluid throughout the body.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Detection of lesions
time frame: Up to 4 years
description: Effectiveness of WBMRI DETECT for the detection of lesions in MM patients will be compared to WBMRI Diffusion Weighted Imaging (DWI). A combination of clinical MRI, whole body x-ray, FDG PET, and bone marrow biopsy will be used as the reference standard.
The number of lesions identified on WBMRI-DETECT will be compared to the number of lesions identified on WBMRI-DWI. The sensitivity and specificity of WBMRI-DETECT and WBMRI-DWI will be calculated using the reference standard.
measure: Assessment of therapy response
time frame: Up to 4 years
description: Effectiveness of WBMRI for assessing therapy response will be compared to the current standard of care using FDG PET and bone marrow biopsy as the validation standard.
The percentage increase in fat fraction measured using WBMRI-DETECT and the percentage increase in apparent diffusion coefficient (ADC) measured using WBMRI-DWI will be used to assess the effectiveness of WBMRI in measuring therapy response. The percentage change in SUVmax measured on PET/CT will be used as the reference standard.
measure: Progression Free Survival (PFS)
time frame: Up to 4 years
description: Will determine if WBMRI prognosis is at baseline, after 4-6 weeks of induction therapy, and before maintenance therapy is associated with PFS.
measure: Overall Survival (OS)
time frame: Up to 4 years
description: Will determine if WBMRI prognosis is at baseline, after 4-6 weeks of induction therapy, and before maintenance therapy is associated with OS.
arm group label: Multiple Myeloma Patients
arm group type: Experimental
description: Patients with pathologically confirmed myeloma for cross-sectional study (detection) or scheduled to undergo induction therapy (or have gone 1-2 cycles of induction therapy), followed by either bone marrow transplantation or consolidation therapy for longitudinal study (therapy response assessment).
intervention type: Procedure
intervention name: WBMRI
description: WBMRI will be performed either at 1 time point for cross-sectional study or at 4 timepoints for the longitudinal study at the following time points.
Baseline: (before or after 1-2 cycles of induction therapy)
Between Week 12 - 24 (before Bone Marrow Transplant or undergoing consolidation therapy)
Between Week 24 - 36 (before starting maintenance therapy)
Between Week 60 - 72 (post bone marrow transplant or consolidation therapy and after approximately 9 months of maintenance therapy)
arm group label: Multiple Myeloma Patients
intervention type: Procedure
intervention name: Positron Emission Tomography/Computed Tomography (PET/CT)
description: PET/CT will be performed at at 1 time point for cross-sectional study or at 4 timepoints for the longitudinal study at the following time points.
Baseline: (before or after 1-2 cycles of induction therapy)
Between Week 12 - 24 (before Bone Marrow Transplant or undergoing consolidation therapy)
Between Week 24 - 36 (before starting maintenance therapy)
Between Week 60 - 72 (post bone marrow transplant or consolidation therapy and after approximately 9 months of maintenance therapy)
arm group label: Multiple Myeloma Patients
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ananth Madhuranthakam, PhD
role: Principal Investigator
affiliation: UT Southwestern Medical Center
last name: Kelli Key, PhD
phone: 214-648-8152
email: Kelli.Key@UTSouthwestern.edu
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Texas Southwestern Medical Center
investigator full name: Ananth Madhuranthakam
investigator title: Associate Professor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
sharing ipd: No