<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/NCT03804424</url>
  </required_header>
  <id_info>
    <org_study_id>201807197</org_study_id>
    <nct_id>NCT03804424</nct_id>
  </id_info>
  <brief_title>64Cu-LLP2A for Imaging Multiple Myeloma</brief_title>
  <official_title>Early Phase I Evaluation of 64Cu-LLP2A for Imaging Multiple Myeloma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Washington University School of Medicine</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators are performing a trial with goals to demonstrate the feasibility of imaging&#xD;
      multiple myeloma (MM) patients with 64Cu-LLP2A-positron emission tomography (PET)/magnetic&#xD;
      resonance (MR). The investigators suggest that 64Cu-LLP2A will allow for an accurate&#xD;
      molecular imaging of MM lesions, which will have an important impact on early stage disease&#xD;
      detection and in the long term on the initiation and choice of therapy in these patients.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 20, 2018</start_date>
  <completion_date type="Anticipated">November 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">November 30, 2024</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>Single (Investigator)</masking>
    <masking_description>Images will be assessed by independent observers (nuclear medicine expert in evaluating PET images using novel radiotracers, and MR radiologist expert in evaluating MR images), who will initially be blinded to all clinical information available (such as tumor size and location), which will be followed by un-blinded combined reading of the PET and MR images</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Feasibility of imaging MM patients with 64Cu-LLP2A-PET/MR as measured by average organ activity concentration of 64Cu-LLP2A</measure>
    <time_frame>Up to 30 hours after imaging</time_frame>
    <description>-Average organ activity concentration will be measured and decay corrected by utilizing regions of interest (ROIs) drawn around all organs visible on 64Cu-LLP2A images. Activity organ residence times will be calculated by numerical or analytical integration of the time-activity curves. Uptake/clearance functional fits of mono or bi-exponential functions will be performed and analytical integration, accounted for physical delay, will be performed. The calculated residence times will be used with the program OLINDA/EXM for 64Cu and using the adult human (male/femal) model to calculate the individual organ radiation dose, the whole-body dose, and the effective dose</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Feasibility of imaging MM patients with 64Cu-LLP2A-PET/MR as measured by the number of participants who experience an adverse event related to 64Cu-LLP2A</measure>
    <time_frame>Through 48 hours after last administration of 64Cu-LLP2A (estimated to be at most 4 days)</time_frame>
    <description>-The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Feasibility of imaging MM patients with 64Cu-LLP2A-PET/MR as measured by the optimal image time after injection of 64Cu-LLP2A</measure>
    <time_frame>Up to 30 hours after imaging</time_frame>
    <description>-The optimal imaging time after injection yields the best image quality and tumor-to-non-tumor ratio for visual and quantitative analysis of the lesions</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Feasibility of imaging MM patients with 64Cu-LLP2A-PET/MR as measured by image quality of 64Cu-LLP2A-PET/MR images</measure>
    <time_frame>Up to 30 hours after imaging</time_frame>
    <description>Overall PET image quality will be graded visually (using 4-point scale with 1 being the worst and poor quality, not acceptable for diagnostic interpretation and 4 being good image quality, similar to routine clinical studies).&#xD;
The images will be assessed by independent observers (a nuclear medicine expert in evaluating PET images using novel radiotracers, and a MR radiologist expert in evaluating MR images&#xD;
The images will then be correlated to MRI (and biopsy if available) to assess whether the lesions identified on 64Cu-LLP2A correspond to myeloma lesions</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Feasibility of imaging MM patients with 64Cu-LLP2A-PET/MR as measured by lesion detection of 64Cu-LLP2A-PET/MR images</measure>
    <time_frame>Up to 30 hours after imaging</time_frame>
    <description>-Lesion detection is measured by lesion uptake in comparison with the surrounding tissue</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Comparison of tumor burden (SUVmax) of 64Cu-LLP2A to clinical stage</measure>
    <time_frame>Up to 30 hours after imaging</time_frame>
    <description>-SUVmax is a mathematical measurement of tumor burden seen on images and calculated by the following equation SUVmax= r / (a'/w) where r= radioactivity concentration in tumor (kBq/ml) as measured by the PET scanner within a defined region of interest, a'=the decay corrected amount of injected 64Cu-LLP2A and w= weight of the patient in grams When PET imaging shows uptake of 64Cyu-LLP2A in site(s) of known tumor the SUVmax will be compared to overall clinical stage as a way to compare accuracy of imaging to known clinical stage</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of tumor burden (SUVmax) of 64Cu-LLP2A to clinical tumor measurement of tumor burden as measured by M-protein of myeloma</measure>
    <time_frame>Up to 30 hours after imaging</time_frame>
    <description>SUVmax is a mathematical measurement of tumor burden seen on images and calculated by the following equation SUVmax= r / (a'/w) where r= radioactivity concentration in tumor (kBq/ml) as measured by the PET scanner within a defined region of interest, a'=the decay corrected amount of injected 64Cu-LLP2A and w= weight of the patient in grams When PET imaging shows uptake of 64Cyu-LLP2A in site(s) of known tumor the SUVmax will be compared to clinical measurement of tumor burden as seen by the laboratory values for M-protein (lab measurement for myeloma gamma globulin which is increased in multiple myleom due to an abnormal monoclonal proliferation of plasma cells)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparision of tumor burden (SUVmax) of 64Cu-LLP2A to clinical measurement of tumor burden as measured by the plasma cell fraction within the bone marrow</measure>
    <time_frame>Up to 30 hours after imaging</time_frame>
    <description>Hierarchical models will be used to estimate the correlation of SUVmax with M-protein expression&#xD;
Variance components models will be fit to identify component (proportion) of total variance</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">36</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>Cohort 1: Pilot 64Cu-LLP2A Imaging</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>16 adult individuals (6-8 patients with known MM; 6-10 healthy volunteers)&#xD;
All subjects who enter the study in Cohort 1 will be injected with up to 11 mCi of 64Cu-LLP2A and will undergo body imaging at least twice within 0-30 hrs following administration of 64Cu-LLP2A to study tracer biodistribution and calculate human dosimetry&#xD;
6 subjects will also undergo dynamic study for 60 mins immediately after administration of 64Cu-LLP2A.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2: Quantitative 64Cu-LLP2A Imaging</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>20 patients with MM will be recruited&#xD;
Subjects who enter on study in Cohort 2 will undergo a 60-min dynamic imaging over the known site of disease (OR pelvis and lower lumbar spine, if no site of disease is known). Following a simple DIXON MRI or low dose CT scan for attenuation correction, subjects will be injected with a dose of up to11 mCi of 64Cu-LLP2A and a list mode dynamic imaging acquisition will begin for a total of 60 mins. Following the dynamic study, or at the optimal time point determined from cohort 1 imaging, after a simple DIXON or low dose CT scan for body (top of the head to below the knees) attenuation correction, emission scans (2-5 min per bed position) will be performed</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>64Cu-LLP2A</intervention_name>
    <description>-64Cu-LLP2A, will be manufactured following batch production record at the cyclotron GMP facility (Washington University School of Medicine GMP radiochemistry/cyclotron facility)</description>
    <arm_group_label>Cohort 1: Pilot 64Cu-LLP2A Imaging</arm_group_label>
    <arm_group_label>Cohort 2: Quantitative 64Cu-LLP2A Imaging</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>PET/MR</intervention_name>
    <description>-All PET imaging will be performed as PET/MR or PET/CT</description>
    <arm_group_label>Cohort 1: Pilot 64Cu-LLP2A Imaging</arm_group_label>
    <arm_group_label>Cohort 2: Quantitative 64Cu-LLP2A Imaging</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Blood samples for serum stability</intervention_name>
    <description>-3 venous samples obtained from an IV site separate from the site of 64Cu-LLP2A injection (2 mL each) will be obtained at the following time points: Cohort 1: prior to injection, at completion of dynamic scanning in those who undergo dynamic imaging and at completion of one of the body imaging time points. In those who do not undergo dynamic imaging, prior to injection, and after completing body imaging at 2 of the 3 time points. Cohort 2: subjects will have samples drawn prior to injection, at completion of dynamic scanning, and at completion of body imaging.</description>
    <arm_group_label>Cohort 1: Pilot 64Cu-LLP2A Imaging</arm_group_label>
    <arm_group_label>Cohort 2: Quantitative 64Cu-LLP2A Imaging</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Blood samples for metabolite analysis</intervention_name>
    <description>-Typically, 2 blood samples obtained from an IV site separate from the site of 64Cu-LLP2A injection (preferably 1 within the first 5 min and 1 at the completion of the first hour of imaging) will be obtained.</description>
    <arm_group_label>Cohort 1: Pilot 64Cu-LLP2A Imaging</arm_group_label>
    <arm_group_label>Cohort 2: Quantitative 64Cu-LLP2A Imaging</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Urine sample</intervention_name>
    <description>-Cohort 1 only</description>
    <arm_group_label>Cohort 1: Pilot 64Cu-LLP2A Imaging</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Tumor biopsy</intervention_name>
    <description>-Cohort 2 only and only if there hasn't been a recent biopsy of disease</description>
    <arm_group_label>Cohort 2: Quantitative 64Cu-LLP2A Imaging</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Electrocardiogram</intervention_name>
    <description>-A standard 12-lead ECG will be obtained on all subjects at baseline (within 30 mins prior to injection of 64Cu-LLP2A), and at least 60 minutes post injection or prior to study discharge</description>
    <arm_group_label>Cohort 1: Pilot 64Cu-LLP2A Imaging</arm_group_label>
    <arm_group_label>Cohort 2: Quantitative 64Cu-LLP2A Imaging</arm_group_label>
    <other_name>ECG</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>PET/CT</intervention_name>
    <description>-All PET imaging will be performed as PET/MR or PET/CT</description>
    <arm_group_label>Cohort 1: Pilot 64Cu-LLP2A Imaging</arm_group_label>
    <arm_group_label>Cohort 2: Quantitative 64Cu-LLP2A Imaging</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult patients 18 years of age or older with clinically or pathologically defined MM&#xD;
             in accordance with International Myeloma Working Group or as stated in office note /&#xD;
             clinical assessment from treating physician.&#xD;
&#xD;
             *All types of active myeloma are eligible including both newly diagnosed and&#xD;
             previously treated provided plans are to start a new treatment or restart a prior&#xD;
             treatment.&#xD;
&#xD;
          -  Healthy Volunteer Subjects: Adult 18 years of age or older with no known hematologic&#xD;
             disorder such as anemia, leukemia, etc. who is considered healthy based on assessment&#xD;
             by PI. (Cohort 1 only).&#xD;
&#xD;
          -  Able to give informed consent.&#xD;
&#xD;
          -  Does not have any exclusions related to PET/MR imaging: No implanted medical devices&#xD;
             such as: pacemaker, defibrillator, neurostimulator, artificial heart valve, cerebral&#xD;
             aneurysm clips, no accidental exposure to metal fragments (if applicable)&#xD;
&#xD;
          -  If applicable for administration of contrast with MRI imaging subject must have a&#xD;
             calculated GFR of at least 60 mg/mL/1.73 m^2.&#xD;
&#xD;
          -  Not currently pregnant or nursing: Subject must be surgically sterile (has had a&#xD;
             documented bilateral oophorectomy and/or documented hysterectomy), post-menopausal&#xD;
             (cessation of menses for more than 1 year), non-lactating, or of childbearing&#xD;
             potential for whom a urine pregnancy test (with the test performed within the 24 hour&#xD;
             period immediately prior to administration of 64Cu-LLP2A) is negative.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with other invasive malignancies, with the exception of non-melanoma skin&#xD;
             cancer, who had (or have) any evidence of the other cancer present within the last 5&#xD;
             years.&#xD;
&#xD;
          -  Unable to tolerate up to 90 min of PET/MR or PET/CT imaging per imaging session.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Farrokh Dehdashti, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Washington University School of Medicine</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Farrokh Dehdashti, M.D.</last_name>
    <phone>314-362-1474</phone>
    <email>dehdashtif@wustl.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Jennifer Frye, CNMT, CCRC</last_name>
    <phone>314-747-1604</phone>
    <email>fryej@wustl.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Farrokh Dehdashti, M.D.</last_name>
      <phone>314-362-1474</phone>
      <email>dehdashtif@wustl.edu</email>
    </contact>
    <contact_backup>
      <last_name>Jennifer Frye, CNMT, CCRC</last_name>
      <phone>314-747-1604</phone>
      <email>fryej@wustl.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Farrokh Dehdashti, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Ravi Vij, M.D.</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Korresh Shoghi, Ph.D.</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Richard Laforest, Ph.D.</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Amber Salter, Ph.D.</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Tyler Fraum, M.D.</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.siteman.wustl.edu</url>
    <description>Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine</description>
  </link>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>December 10, 2018</study_first_submitted>
  <study_first_submitted_qc>January 10, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 15, 2019</study_first_posted>
  <last_update_submitted>July 30, 2023</last_update_submitted>
  <last_update_submitted_qc>July 30, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 1, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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>Yes</sharing_ipd>
    <ipd_description>A primary means of sharing data will be through publication in peer-reviewed journals. As required by the NIH Public Access Policy, the investigators will submit to the NIH National Library of Medicine's PubMed Central an electronic version of final manuscripts upon acceptance for publication, resulting from research supported by these funds, in whole or in part, with direct costs from NIH.&#xD;
It is expected that approximately 1-2 presentations at national meetings&#xD;
Early phase I evaluation of 64Cu-LLP2A for imaging multiple myeloma will generate imaging, safety and dosimetry data from PET/CT and MR studies of 64Cu-LLP2A. Serum markers such as M-protein, plasma cell density and immunohistochemistry will be correlated with imaging, in order to understand the interaction of 64Cu-LLP2A with VLA-4 in vivo. It is the explicit intention that these data will be placed in a readily accessible public database.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_time_frame>All efforts will be made to rapidly release data through publications of the results as quickly as it is possible to analyze the experiments.</ipd_time_frame>
  </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/NCT03804424
org study id: 201807197
nct id: NCT03804424
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The investigators are performing a trial with goals to demonstrate the feasibility of imaging
      multiple myeloma (MM) patients with 64Cu-LLP2A-positron emission tomography (PET)/magnetic
      resonance (MR). The investigators suggest that 64Cu-LLP2A will allow for an accurate
      molecular imaging of MM lesions, which will have an important impact on early stage disease
      detection and in the long term on the initiation and choice of therapy in these patients.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Diagnostic
masking: Single (Investigator)
masking description: Images will be assessed by independent observers (nuclear medicine expert in evaluating PET images using novel radiotracers, and MR radiologist expert in evaluating MR images), who will initially be blinded to all clinical information available (such as tumor size and location), which will be followed by un-blinded combined reading of the PET and MR images
measure: Feasibility of imaging MM patients with 64Cu-LLP2A-PET/MR as measured by average organ activity concentration of 64Cu-LLP2A
time frame: Up to 30 hours after imaging
description: -Average organ activity concentration will be measured and decay corrected by utilizing regions of interest (ROIs) drawn around all organs visible on 64Cu-LLP2A images. Activity organ residence times will be calculated by numerical or analytical integration of the time-activity curves. Uptake/clearance functional fits of mono or bi-exponential functions will be performed and analytical integration, accounted for physical delay, will be performed. The calculated residence times will be used with the program OLINDA/EXM for 64Cu and using the adult human (male/femal) model to calculate the individual organ radiation dose, the whole-body dose, and the effective dose
measure: Feasibility of imaging MM patients with 64Cu-LLP2A-PET/MR as measured by the number of participants who experience an adverse event related to 64Cu-LLP2A
time frame: Through 48 hours after last administration of 64Cu-LLP2A (estimated to be at most 4 days)
description: -The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.
measure: Feasibility of imaging MM patients with 64Cu-LLP2A-PET/MR as measured by the optimal image time after injection of 64Cu-LLP2A
time frame: Up to 30 hours after imaging
description: -The optimal imaging time after injection yields the best image quality and tumor-to-non-tumor ratio for visual and quantitative analysis of the lesions
measure: Feasibility of imaging MM patients with 64Cu-LLP2A-PET/MR as measured by image quality of 64Cu-LLP2A-PET/MR images
time frame: Up to 30 hours after imaging
description: Overall PET image quality will be graded visually (using 4-point scale with 1 being the worst and poor quality, not acceptable for diagnostic interpretation and 4 being good image quality, similar to routine clinical studies).
The images will be assessed by independent observers (a nuclear medicine expert in evaluating PET images using novel radiotracers, and a MR radiologist expert in evaluating MR images
The images will then be correlated to MRI (and biopsy if available) to assess whether the lesions identified on 64Cu-LLP2A correspond to myeloma lesions
measure: Feasibility of imaging MM patients with 64Cu-LLP2A-PET/MR as measured by lesion detection of 64Cu-LLP2A-PET/MR images
time frame: Up to 30 hours after imaging
description: -Lesion detection is measured by lesion uptake in comparison with the surrounding tissue
measure: Comparison of tumor burden (SUVmax) of 64Cu-LLP2A to clinical stage
time frame: Up to 30 hours after imaging
description: -SUVmax is a mathematical measurement of tumor burden seen on images and calculated by the following equation SUVmax= r / (a'/w) where r= radioactivity concentration in tumor (kBq/ml) as measured by the PET scanner within a defined region of interest, a'=the decay corrected amount of injected 64Cu-LLP2A and w= weight of the patient in grams When PET imaging shows uptake of 64Cyu-LLP2A in site(s) of known tumor the SUVmax will be compared to overall clinical stage as a way to compare accuracy of imaging to known clinical stage
measure: Comparison of tumor burden (SUVmax) of 64Cu-LLP2A to clinical tumor measurement of tumor burden as measured by M-protein of myeloma
time frame: Up to 30 hours after imaging
description: SUVmax is a mathematical measurement of tumor burden seen on images and calculated by the following equation SUVmax= r / (a'/w) where r= radioactivity concentration in tumor (kBq/ml) as measured by the PET scanner within a defined region of interest, a'=the decay corrected amount of injected 64Cu-LLP2A and w= weight of the patient in grams When PET imaging shows uptake of 64Cyu-LLP2A in site(s) of known tumor the SUVmax will be compared to clinical measurement of tumor burden as seen by the laboratory values for M-protein (lab measurement for myeloma gamma globulin which is increased in multiple myleom due to an abnormal monoclonal proliferation of plasma cells)
measure: Comparision of tumor burden (SUVmax) of 64Cu-LLP2A to clinical measurement of tumor burden as measured by the plasma cell fraction within the bone marrow
time frame: Up to 30 hours after imaging
description: Hierarchical models will be used to estimate the correlation of SUVmax with M-protein expression
Variance components models will be fit to identify component (proportion) of total variance
arm group label: Cohort 1: Pilot 64Cu-LLP2A Imaging
arm group type: Experimental
description: 16 adult individuals (6-8 patients with known MM; 6-10 healthy volunteers)
All subjects who enter the study in Cohort 1 will be injected with up to 11 mCi of 64Cu-LLP2A and will undergo body imaging at least twice within 0-30 hrs following administration of 64Cu-LLP2A to study tracer biodistribution and calculate human dosimetry
6 subjects will also undergo dynamic study for 60 mins immediately after administration of 64Cu-LLP2A.
arm group label: Cohort 2: Quantitative 64Cu-LLP2A Imaging
arm group type: Experimental
description: 20 patients with MM will be recruited
Subjects who enter on study in Cohort 2 will undergo a 60-min dynamic imaging over the known site of disease (OR pelvis and lower lumbar spine, if no site of disease is known). Following a simple DIXON MRI or low dose CT scan for attenuation correction, subjects will be injected with a dose of up to11 mCi of 64Cu-LLP2A and a list mode dynamic imaging acquisition will begin for a total of 60 mins. Following the dynamic study, or at the optimal time point determined from cohort 1 imaging, after a simple DIXON or low dose CT scan for body (top of the head to below the knees) attenuation correction, emission scans (2-5 min per bed position) will be performed
intervention type: Drug
intervention name: 64Cu-LLP2A
description: -64Cu-LLP2A, will be manufactured following batch production record at the cyclotron GMP facility (Washington University School of Medicine GMP radiochemistry/cyclotron facility)
arm group label: Cohort 1: Pilot 64Cu-LLP2A Imaging
arm group label: Cohort 2: Quantitative 64Cu-LLP2A Imaging
intervention type: Device
intervention name: PET/MR
description: -All PET imaging will be performed as PET/MR or PET/CT
arm group label: Cohort 1: Pilot 64Cu-LLP2A Imaging
arm group label: Cohort 2: Quantitative 64Cu-LLP2A Imaging
intervention type: Procedure
intervention name: Blood samples for serum stability
description: -3 venous samples obtained from an IV site separate from the site of 64Cu-LLP2A injection (2 mL each) will be obtained at the following time points: Cohort 1: prior to injection, at completion of dynamic scanning in those who undergo dynamic imaging and at completion of one of the body imaging time points. In those who do not undergo dynamic imaging, prior to injection, and after completing body imaging at 2 of the 3 time points. Cohort 2: subjects will have samples drawn prior to injection, at completion of dynamic scanning, and at completion of body imaging.
arm group label: Cohort 1: Pilot 64Cu-LLP2A Imaging
arm group label: Cohort 2: Quantitative 64Cu-LLP2A Imaging
intervention type: Procedure
intervention name: Blood samples for metabolite analysis
description: -Typically, 2 blood samples obtained from an IV site separate from the site of 64Cu-LLP2A injection (preferably 1 within the first 5 min and 1 at the completion of the first hour of imaging) will be obtained.
arm group label: Cohort 1: Pilot 64Cu-LLP2A Imaging
arm group label: Cohort 2: Quantitative 64Cu-LLP2A Imaging
intervention type: Procedure
intervention name: Urine sample
description: -Cohort 1 only
arm group label: Cohort 1: Pilot 64Cu-LLP2A Imaging
intervention type: Procedure
intervention name: Tumor biopsy
description: -Cohort 2 only and only if there hasn't been a recent biopsy of disease
arm group label: Cohort 2: Quantitative 64Cu-LLP2A Imaging
intervention type: Procedure
intervention name: Electrocardiogram
description: -A standard 12-lead ECG will be obtained on all subjects at baseline (within 30 mins prior to injection of 64Cu-LLP2A), and at least 60 minutes post injection or prior to study discharge
arm group label: Cohort 1: Pilot 64Cu-LLP2A Imaging
arm group label: Cohort 2: Quantitative 64Cu-LLP2A Imaging
other name: ECG
intervention type: Device
intervention name: PET/CT
description: -All PET imaging will be performed as PET/MR or PET/CT
arm group label: Cohort 1: Pilot 64Cu-LLP2A Imaging
arm group label: Cohort 2: Quantitative 64Cu-LLP2A Imaging
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Farrokh Dehdashti, M.D.
role: Principal Investigator
affiliation: Washington University School of Medicine
last name: Farrokh Dehdashti, M.D.
phone: 314-362-1474
email: dehdashtif@wustl.edu
last name: Jennifer Frye, CNMT, CCRC
phone: 314-747-1604
email: fryej@wustl.edu
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
country: United States
url: http://www.siteman.wustl.edu
description: Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
sharing ipd: Yes
ipd description: A primary means of sharing data will be through publication in peer-reviewed journals. As required by the NIH Public Access Policy, the investigators will submit to the NIH National Library of Medicine's PubMed Central an electronic version of final manuscripts upon acceptance for publication, resulting from research supported by these funds, in whole or in part, with direct costs from NIH.
It is expected that approximately 1-2 presentations at national meetings
Early phase I evaluation of 64Cu-LLP2A for imaging multiple myeloma will generate imaging, safety and dosimetry data from PET/CT and MR studies of 64Cu-LLP2A. Serum markers such as M-protein, plasma cell density and immunohistochemistry will be correlated with imaging, in order to understand the interaction of 64Cu-LLP2A with VLA-4 in vivo. It is the explicit intention that these data will be placed in a readily accessible public database.
ipd info type: Study Protocol
ipd time frame: All efforts will be made to rapidly release data through publications of the results as quickly as it is possible to analyze the experiments.