<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/NCT03832127</url>
  </required_header>
  <id_info>
    <org_study_id>RC18_0055</org_study_id>
    <nct_id>NCT03832127</nct_id>
  </id_info>
  <brief_title>Evaluation of PET 18F-Fludarabine for the Initial Assessment and End-treatment of Symptomatic Multiple Myeloma Patients</brief_title>
  <acronym>Myelofludate</acronym>
  <official_title>Exploratory Study Evaluating the Interest of PET to 18F-Fludarabine for the Initial Assessment and End-treatment Evaluation of Patients With Symptomatic Multiple Myeloma in the First Line of Treatment, Not Candidates for Marrow Autograft</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nantes University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Cyceron</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Nantes University Hospital</source>
  <oversight_info>
    <has_dmc>No</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>
      The objective of this exploratory study is to evaluate, for the first time, the sensitivity&#xD;
      of 18F-Fludarabine to the initial diagnosis of MM compared to FDG-PET and MRI. The interest&#xD;
      of this molecule will also be investigated as part of the end-of-treatment therapeutic&#xD;
      evaluation.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">April 1, 2022</start_date>
  <completion_date type="Anticipated">April 1, 2026</completion_date>
  <primary_completion_date type="Anticipated">April 1, 2024</primary_completion_date>
  <phase>Phase 1</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 sensitivity of the lesions (osseous and extra-osseous) of 18Fludarabine PET (FludaTEP)</measure>
    <time_frame>Before treatment</time_frame>
    <description>The sensitivity of the initial FludaTEP will be evaluated using an optimal reading mode lesion analysis (ie by consensus of experts) by defining :&#xD;
True positive:&#xD;
positive lesion with 18F-Fludarabine and positive with PET-FDG or MRI&#xD;
or positive lesion with 18-F-Fludarabine, negative with PET-FDG and MRI, but confirmed by further complementary imaging (CT) or histological examination, or confirmed at follow-up&#xD;
False negative:&#xD;
-negative lesion with 18F-Fludarabine and positive FDG-PET and / or MR Lesions positivity in PET-FDG and MRI will be assessed by central reading done by consensus of experts. Lesions positivity with 18F-Fludarabine will be defined by central reading assessed by 2 nuclear physicians experts in hematology with no access to the other exams' results.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To evaluate the specificity and the positive and negative predictive values of the FludaTEP for the initial assessment through an optimal reading mode.</measure>
    <time_frame>Before treatment</time_frame>
    <description>The specificity, positive predictive value (PPV) and negative predictive value (NPV) of the FludaTEP for the initial assessment will be assessed through an optimal reading mode lesion analysis (ie by consensus of experts) using same true positive and false positive définitions as for the main endpoint and defining: -positive lesion with 18F-Fludarabine but not found or confirmed on an histological examination, or other imaging technique (PET-FDG, MRI +/- Scan) or at follow-up&#xD;
True negative:&#xD;
-negative lesion with 18F-Fludarabine and negative with FDG-PET and MRI</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate the sensitivity, specificity, and positive and negative predictive values of the FludaTEP for the initial balance according to the local reading</measure>
    <time_frame>Before treatment</time_frame>
    <description>The specificity, positive predictive value (PPV) and negative predictive value (NPV) of the FludaTEP for the initial balance will be evaluated through lesion analysis based on the local reading investigator center reading using definitions of VP, VN, FP, and FN described above.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate the prognostic impact of FDG-PET and FludaTEP on the number of lesions detected by each imaging technique in a population of MM patients in the 1st line therapeutic but not candidates for marrow autograft.</measure>
    <time_frame>After treatment</time_frame>
    <description>The prognostic impact of FDG-PET and FludaTEP as a function of the number of lesions detected by each imaging technique will be evaluated by evaluating the impact of these data on progression-free survival and overall survival. Progression-free survival is defined as the time between the beginning of treatment of the disease and relapse or progression. Overall survival is defined as the time between the start of treatment and death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate the prognostic impact of FludaTEP on the initial assessment and for the end-of-treatment therapeutic evaluation</measure>
    <time_frame>Before and After treatment</time_frame>
    <description>The prognostic impact of FludaTEP on the initial assessment and for the end-of-treatment therapeutic evaluation will be determined by evaluating the impact of a decrease and a negation of the signal in imaging on an increase in progression-free survival and overall survival.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate in a population of MM patients the existence of a correlation between the 18Fludarabine and FDG uptake intensities</measure>
    <time_frame>Before and After treatment</time_frame>
    <description>Correlations between the 18Fludarabine and FDG uptake intensities assessed by SUVs and the quantitative expression of markers measured in flow cytometry and cytogenetic data (in particular the expression of the coding gene for hexokinases) will be measured using Spearman's correlation coefficient.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate in a population of MM patients the existence of a correlation between the 18Fludarabine and FDG uptake intensities and the cytogenetic data Tolerance to 18F-Fludarabine</measure>
    <time_frame>Before and After treatment</time_frame>
    <description>Tolerance to 18F-Fludarabine will be evaluated by clinical monitoring during 2 hours following the 18F-Fludarabine injection. Clinical data will be taken prior to the 18F-Fludarabine injection, prior to the data capture at 60min and after the last data capture.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">35</enrollment>
  <condition>Myeloma</condition>
  <arm_group>
    <arm_group_label>Fludatep</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>PET with 18F-Fludarabine</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>18F-Fludarabine</intervention_name>
    <description>Two PET with 18F-Fludarabine : one at Baseline, the second one at the end of treatment of myeloma</description>
    <arm_group_label>Fludatep</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Symptomatic MM in the first line in patients who are not candidates for autologous&#xD;
             bone marrow transplantation.&#xD;
&#xD;
          -  Patients eligible for one of the treatments considered as standard in a patient who is&#xD;
             not eligible for autograft, according to ESMO's European recommendations&#xD;
&#xD;
          -  MM with measurable disease either by the serum evaluation of the monoclonal component&#xD;
             or by the determination of free light chains (serum or urinary).&#xD;
&#xD;
          -  Patient affiliated with a social insurance scheme&#xD;
&#xD;
          -  The patient must understand and voluntarily sign the informed consent form&#xD;
&#xD;
          -  Women of childbearing potential must have a serum pregnancy test (performed within 2&#xD;
             days before each PET scan.)&#xD;
&#xD;
          -  Women of childbearing potential must use an effective contraceptive method throughout&#xD;
             the course of the study and for 30 days after the last PET.&#xD;
&#xD;
          -  Male patients (vasectomised or not) with a pregnant partner or a partner of&#xD;
             childbearing potential must use a condom and a spermicide until 90 days after the last&#xD;
             PET.&#xD;
&#xD;
          -  HIV serology known to be negative&#xD;
&#xD;
          -  Karnofsky ≥ 70 or ECOG 0-1&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age under 18 years&#xD;
&#xD;
          -  Pregnancy or breastfeeding&#xD;
&#xD;
          -  Male or female refusing birth control conditions&#xD;
&#xD;
          -  Primary AL amyloidosis and myeloma complicated by amyloidosis&#xD;
&#xD;
          -  Neutropenia &lt;1000 PN / mm3&#xD;
&#xD;
          -  Thrombocytopenia &lt;70,000 / mm3&#xD;
&#xD;
          -  Hepatic impairment: bilirubin&gt; 35μmol / L and SGOT, SGPT, alkaline phosphatase greater&#xD;
             than 3 N&#xD;
&#xD;
          -  Renal impairment defined by creatinine clearance &lt;50 ml / min&#xD;
&#xD;
          -  History of other malignancies with the exception of basal cell carcinoma and stage I&#xD;
             cervical cancer&#xD;
&#xD;
          -  Severe active infection&#xD;
&#xD;
          -  Active infection with known hepatitis B or C virus.&#xD;
&#xD;
          -  Patient with insulin-dependent or non-insulin-dependent diabetes mellitus.&#xD;
&#xD;
          -  Intolerance or known allergy to any of the study drugs or any of its analogues&#xD;
&#xD;
          -  Psychiatric illness that may interfere with participation in the study&#xD;
&#xD;
          -  Patient under safeguard of justice&#xD;
&#xD;
          -  Intellectual inability to sign informed consent&#xD;
&#xD;
          -  Persons protected by law&#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_contact>
    <last_name>Caroline Bodet-Milin, MD</last_name>
    <phone>33240084136</phone>
    <email>caroline.milin@chu-nantes.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>CHU d'Angers</name>
      <address>
        <city>Angers</city>
        <zip>49100</zip>
        <country>France</country>
      </address>
    </facility>
    <contact>
      <last_name>Pacôme Fosse, MD</last_name>
    </contact>
    <investigator>
      <last_name>Pacôme Fosse, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU de Brest</name>
      <address>
        <city>Brest</city>
        <zip>29000</zip>
        <country>France</country>
      </address>
    </facility>
    <contact>
      <last_name>Pierre Yves Salaün, MD</last_name>
    </contact>
    <investigator>
      <last_name>Pierre Yvese Salaün, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU de Caen</name>
      <address>
        <city>Caen</city>
        <zip>14000</zip>
        <country>France</country>
      </address>
    </facility>
    <contact>
      <last_name>Nicolas Aide, MD</last_name>
    </contact>
    <investigator>
      <last_name>Nicolas Aide, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU de Nantes</name>
      <address>
        <city>Nantes</city>
        <zip>44093</zip>
        <country>France</country>
      </address>
    </facility>
    <contact>
      <last_name>Caroline Bodet-Milin, MD</last_name>
    </contact>
    <investigator>
      <last_name>Caroline bodet Mion, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centre Eugène Marquis</name>
      <address>
        <city>Rennes</city>
        <zip>35000</zip>
        <country>France</country>
      </address>
    </facility>
    <contact>
      <last_name>Anne Devillers, MD</last_name>
    </contact>
    <investigator>
      <last_name>Anne Devillers, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU de Rennes</name>
      <address>
        <city>Rennes</city>
        <zip>35000</zip>
        <country>France</country>
      </address>
    </facility>
    <contact>
      <last_name>Thierry Lamy, MD</last_name>
    </contact>
    <investigator>
      <last_name>Thierry Lamy, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU de Tours</name>
      <address>
        <city>Tours</city>
        <zip>37000</zip>
        <country>France</country>
      </address>
    </facility>
    <contact>
      <last_name>Maria Joao Santiago-Ribeiro, MD</last_name>
    </contact>
    <investigator>
      <last_name>Maria Joao Santiago-Ribeiro, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>December 2021</verification_date>
  <study_first_submitted>July 20, 2018</study_first_submitted>
  <study_first_submitted_qc>February 4, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 6, 2019</study_first_posted>
  <last_update_submitted>December 24, 2021</last_update_submitted>
  <last_update_submitted_qc>December 24, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">December 28, 2021</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fludarabine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03832127
org study id: RC18_0055
nct id: NCT03832127
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The objective of this exploratory study is to evaluate, for the first time, the sensitivity
      of 18F-Fludarabine to the initial diagnosis of MM compared to FDG-PET and MRI. The interest
      of this molecule will also be investigated as part of the end-of-treatment therapeutic
      evaluation.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Detection of sensitivity of the lesions (osseous and extra-osseous) of 18Fludarabine PET (FludaTEP)
time frame: Before treatment
description: The sensitivity of the initial FludaTEP will be evaluated using an optimal reading mode lesion analysis (ie by consensus of experts) by defining :
True positive:
positive lesion with 18F-Fludarabine and positive with PET-FDG or MRI
or positive lesion with 18-F-Fludarabine, negative with PET-FDG and MRI, but confirmed by further complementary imaging (CT) or histological examination, or confirmed at follow-up
False negative:
-negative lesion with 18F-Fludarabine and positive FDG-PET and / or MR Lesions positivity in PET-FDG and MRI will be assessed by central reading done by consensus of experts. Lesions positivity with 18F-Fludarabine will be defined by central reading assessed by 2 nuclear physicians experts in hematology with no access to the other exams' results.
measure: To evaluate the specificity and the positive and negative predictive values of the FludaTEP for the initial assessment through an optimal reading mode.
time frame: Before treatment
description: The specificity, positive predictive value (PPV) and negative predictive value (NPV) of the FludaTEP for the initial assessment will be assessed through an optimal reading mode lesion analysis (ie by consensus of experts) using same true positive and false positive définitions as for the main endpoint and defining: -positive lesion with 18F-Fludarabine but not found or confirmed on an histological examination, or other imaging technique (PET-FDG, MRI +/- Scan) or at follow-up
True negative:
-negative lesion with 18F-Fludarabine and negative with FDG-PET and MRI
measure: To evaluate the sensitivity, specificity, and positive and negative predictive values of the FludaTEP for the initial balance according to the local reading
time frame: Before treatment
description: The specificity, positive predictive value (PPV) and negative predictive value (NPV) of the FludaTEP for the initial balance will be evaluated through lesion analysis based on the local reading investigator center reading using definitions of VP, VN, FP, and FN described above.
measure: To evaluate the prognostic impact of FDG-PET and FludaTEP on the number of lesions detected by each imaging technique in a population of MM patients in the 1st line therapeutic but not candidates for marrow autograft.
time frame: After treatment
description: The prognostic impact of FDG-PET and FludaTEP as a function of the number of lesions detected by each imaging technique will be evaluated by evaluating the impact of these data on progression-free survival and overall survival. Progression-free survival is defined as the time between the beginning of treatment of the disease and relapse or progression. Overall survival is defined as the time between the start of treatment and death.
measure: To evaluate the prognostic impact of FludaTEP on the initial assessment and for the end-of-treatment therapeutic evaluation
time frame: Before and After treatment
description: The prognostic impact of FludaTEP on the initial assessment and for the end-of-treatment therapeutic evaluation will be determined by evaluating the impact of a decrease and a negation of the signal in imaging on an increase in progression-free survival and overall survival.
measure: Evaluate in a population of MM patients the existence of a correlation between the 18Fludarabine and FDG uptake intensities
time frame: Before and After treatment
description: Correlations between the 18Fludarabine and FDG uptake intensities assessed by SUVs and the quantitative expression of markers measured in flow cytometry and cytogenetic data (in particular the expression of the coding gene for hexokinases) will be measured using Spearman's correlation coefficient.
measure: Evaluate in a population of MM patients the existence of a correlation between the 18Fludarabine and FDG uptake intensities and the cytogenetic data Tolerance to 18F-Fludarabine
time frame: Before and After treatment
description: Tolerance to 18F-Fludarabine will be evaluated by clinical monitoring during 2 hours following the 18F-Fludarabine injection. Clinical data will be taken prior to the 18F-Fludarabine injection, prior to the data capture at 60min and after the last data capture.
arm group label: Fludatep
arm group type: Experimental
description: PET with 18F-Fludarabine
intervention type: Drug
intervention name: 18F-Fludarabine
description: Two PET with 18F-Fludarabine : one at Baseline, the second one at the end of treatment of myeloma
arm group label: Fludatep
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Caroline Bodet-Milin, MD
phone: 33240084136
email: caroline.milin@chu-nantes.fr
facility: 
contact: 
investigator: 
facility: 
contact: 
investigator: 
facility: 
contact: 
investigator: 
facility: 
contact: 
investigator: 
facility: 
contact: 
investigator: 
facility: 
contact: 
investigator: 
facility: 
contact: 
investigator: 
country: France
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Fludarabine
sharing ipd: Undecided