<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/NCT01718366</url>
  </required_header>
  <id_info>
    <org_study_id>GFM-EXVD-AZA-2011-005623-41</org_study_id>
    <nct_id>NCT01718366</nct_id>
  </id_info>
  <brief_title>A Study of Combined Deferasirox, Vitamin D and Azacytidine in High Risk MDS</brief_title>
  <acronym>GFM-EXVD-AZA</acronym>
  <official_title>Phase I-II Study of Association of Deferasirox, Vitamin D and Azacytidine as Treatment of High Risk MDS (IPSS Int-2 and High)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Groupe Francophone des Myelodysplasies</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Novartis</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Groupe Francophone des Myelodysplasies</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Determinate safety and response rate of the association Deferasirox -Vitamine D - Azacitidine&#xD;
      in treatment of high risk MDS&#xD;
&#xD;
      Deferasirox Exjade:&#xD;
&#xD;
      The dose of Deferasirox will be assigned according to the ferritin level. Dose escalation is&#xD;
      scheduled during the phase I, with 5 additional patients per group.&#xD;
&#xD;
      The maximal tolerated dose of Deferasirox will be required for the phase II of the study.&#xD;
&#xD;
      The first dose will be assigned according to the ferritin level of the patient at time of&#xD;
      inclusion:&#xD;
&#xD;
      5 mg/kg/d if the ferritin is &gt;300ng/ml and &lt; 1000ng/ml in Group 1 10 mg/kg/d if the ferritin&#xD;
      is ≥1000ng/ml) in Group 2&#xD;
&#xD;
      Group 1 : Ferritin 300 to 1000ng /ml:&#xD;
&#xD;
        -  cohort 1 : 5 mg/kg/d&#xD;
&#xD;
        -  cohort 2 : 10mg/kg/d&#xD;
&#xD;
        -  cohort 3 : 15 mg/kg/d&#xD;
&#xD;
      Group 2 : Ferritin &gt; 1000ng /ml:&#xD;
&#xD;
        -  cohort 1 : 10 mg/kg/d&#xD;
&#xD;
        -  cohort 2 : 15mg/kg/d&#xD;
&#xD;
        -  cohort 3 : 20 mg/kg/d&#xD;
&#xD;
           5 patients will be treated by cohort. In absence of toxicity (extra-hematological&#xD;
           toxicity grade 3 or 4 or hematological grade 4), 5 additional patients will be included&#xD;
           in the next cohort.&#xD;
&#xD;
      Deferasirox will be administrated once daily during all the study period. Uvedose will be&#xD;
      administrated once weekly during all the study period (100.000 UI P.O).&#xD;
&#xD;
      Azacitidine will be administrated sc at 75 mg/m²/d, during 7 days, J1 to J7 of each&#xD;
      cycles(One cycle is 28 days)&#xD;
&#xD;
      During phase I and II, Deferasirox will always be associated with Vitamin D and Azacitidine&#xD;
&#xD;
      Patients will be received 6 cycles of treatment (except if progression, unacceptable toxicity&#xD;
      or withdrawn of patients occured) After 3 and 6 cycles, an evaluation will be done to&#xD;
      evaluate the efficacy of the treatment.&#xD;
&#xD;
      No dose modification of deferasirox will be done after 3 cycles of treatment except in case&#xD;
      of progression). After 6 cycles, patients with CR, PR, marrow CR or HI will be treated with&#xD;
      the same dose of Deferasirox until progression .&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Deferasirox will be administrated once daily in the morning on an empty stomach, 30 minutes&#xD;
      before meal.&#xD;
&#xD;
      Deferasirox will be stopped if the ferritin level is under 100 ng/ml,and could be restarted&#xD;
      is the ferritin level increase to 200 ng/ml&#xD;
&#xD;
      Uvedose dose could be adjusted according to the phosphocalcic metabolism parameters and the&#xD;
      plasma Vitamin D3 level.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">February 2013</start_date>
  <completion_date type="Anticipated">February 2019</completion_date>
  <primary_completion_date type="Anticipated">February 2019</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>To determine the maximal tolerated dose(MTD</measure>
    <time_frame>6 month of treatment</time_frame>
    <description>patient will be evaluable after at least one cycle. Treatment will be administrated during 6 month and responders will be treated until progression or death</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>MDS</condition>
  <arm_group>
    <arm_group_label>ferritin level &gt;300ng/ml and &lt; 1000ng/ml</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will be included in 2 groups according to the ferritin level at time of inclusion.&#xD;
Patients with the ferritin level &gt;300ng/ml and &lt; 1000ng/ml, will be included in Group 1.&#xD;
Interventions: Deferasirox, Vitamin D (100000/week) and Azacitidine (75 mg/kg/day Day1 today 7)&#xD;
5 patients in each cohort: Cohort 1: Deferasirox: 5mg/kg/d Cohort 2: Deferasirox: 10mg/kg/d Cohort 3: Deferasirox: 15mg/kg/d</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ferritin level &gt; 1000ng/ml</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will be included in 2 groups according to the ferritin level at time of inclusion.&#xD;
Patients with the ferritin level &gt; 1000ng/ml, will be included in Group 2. Intervention: Deferasirox, Vitamin D (100000/week) and Azacitidine (75 mg/kg/day Day1 today 7)&#xD;
5 patients in each cohort: Cohort 1: Deferasirox: 10mg/kg/d Cohort 2: Deferasirox: 15mg/kg/d Cohort 3: Deferasirox: 20mg/kg/d</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Deferasirox, Vitamin D and Azacitidine</intervention_name>
    <description>association of Deferasirox (group 1: 5-10-15/mg/kg/day according to dose level group), Vitamine D (100000U/week) and Azacitidine (75 mg/kg/day day1-day7)</description>
    <arm_group_label>ferritin level &gt; 1000ng/ml</arm_group_label>
    <arm_group_label>ferritin level &gt;300ng/ml and &lt; 1000ng/ml</arm_group_label>
    <other_name>Exjade</other_name>
    <other_name>VitaminD</other_name>
    <other_name>Vidaza</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  High risk MDS, according to OMS classification&#xD;
&#xD;
          -  High risk CMML (WBC &lt; 13 G/L)&#xD;
&#xD;
          -  AREBT of the FAB classification with less than 30% of blastes&#xD;
&#xD;
          -  IPSS&gt;=1.5 (int-2 and high risk)&#xD;
&#xD;
          -  Age &gt;=18y&#xD;
&#xD;
          -  Performance status&lt;=2 (ECOG)&#xD;
&#xD;
          -  Bilirubin and transaminase &lt; 1.5 x ULN&#xD;
&#xD;
          -  Normal renal function&#xD;
&#xD;
          -  Patient not eligible for Allogeneic stem cell transplant&#xD;
&#xD;
          -  Male and female patients must use an effective contraceptive method during the study&#xD;
             and for a minimum of 3 months after study treatment.&#xD;
&#xD;
          -  Agree the need for the use of a condom if engaged in sexual activity with a pregnant&#xD;
             woman or a woman of childbearing potential. during the entire period of treatment,&#xD;
             even if disruption of treatment and during 3 months after end of treatment&#xD;
&#xD;
          -  Male patient: Agree not to conceive during treatment and study drug therapy (including&#xD;
             doses interruptions) and for 3 months after the end of the study drug therapy&#xD;
&#xD;
          -  Agree not to donate semen during study drug therapy and for one week after end of&#xD;
             study drug therapy.&#xD;
&#xD;
          -  Agree to learn about the procedures for preservation of sperm,before starting&#xD;
             treatment&#xD;
&#xD;
          -  Patient be able to adhere to the study visit schedule and other protocol requirements&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Active infection or uncontrolled disease&#xD;
&#xD;
          -  Use of cytotoxic chemotherapeutic agents or experimental agents(agents that are not&#xD;
             commercially available) for the treatment of MDS within 28 days. In case of used of&#xD;
             cytotoxic chemotherapeutic agents or hypomethylating agent a wash out of 3 mont is&#xD;
             required.&#xD;
&#xD;
          -  Active Cancer or Cancer within one year before inclusion&#xD;
&#xD;
          -  Previous calcic urinary lithiasis&#xD;
&#xD;
          -  Previous hyperparathyroid primitive disease or uncontrolled&#xD;
&#xD;
          -  Hypercalcemia, hyperphosphoremia, hypervitaminosis D&#xD;
&#xD;
          -  Patient already include in another experimental study&#xD;
&#xD;
          -  Active infection by HIV, hepatite B or C&#xD;
&#xD;
          -  Pregnant or lactating females&#xD;
&#xD;
          -  Patient not able (medical/psychiatric) to understand and sign the written consent&#xD;
&#xD;
          -  Patients with a ferritin level less than 300ng/ml&#xD;
&#xD;
          -  Patient eligible for an Allogeneic stem cell transplant&#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>Olivier Hermine, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Necker Hospital (Paris)</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Pierre Fenaux, MD</last_name>
    <role>Study Director</role>
    <affiliation>Saint Louis Hospital (Paris)</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Felipe Suarez, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Necker Hospital (Paris)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>GENT</name>
      <address>
        <city>Gent</city>
        <zip>9000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier de La Cote Basque</name>
      <address>
        <city>Bayonne</city>
        <zip>64100</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Avicenne</name>
      <address>
        <city>Bobigny</city>
        <zip>93009</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier de Boulogne sur Mer</name>
      <address>
        <city>Boulogne sur Mer</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Le Mans</name>
      <address>
        <city>Le MANS</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Saint Vincent de Paul</name>
      <address>
        <city>Lille</city>
        <zip>59020</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Limoges</name>
      <address>
        <city>Limoges</city>
        <zip>87042</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Brabois</name>
      <address>
        <city>Nancy</city>
        <zip>54511</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Nantes</name>
      <address>
        <city>Nantes</city>
        <zip>44093</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Catherine de Sienne</name>
      <address>
        <city>Nantes</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital saint Louis</name>
      <address>
        <city>Paris</city>
        <zip>75010</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital cochin</name>
      <address>
        <city>Paris</city>
        <zip>75679</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Necker</name>
      <address>
        <city>Paris</city>
        <zip>75743</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Poitiers</name>
      <address>
        <city>Poitiers</city>
        <zip>86021</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IUCT Oncopole Toulouse</name>
      <address>
        <city>Toulouse</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>France</country>
  </location_countries>
  <verification_date>January 2018</verification_date>
  <study_first_submitted>October 24, 2012</study_first_submitted>
  <study_first_submitted_qc>October 30, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 31, 2012</study_first_posted>
  <last_update_submitted>January 9, 2018</last_update_submitted>
  <last_update_submitted_qc>January 9, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">January 10, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vitamin D</mesh_term>
    <mesh_term>Azacitidine</mesh_term>
    <mesh_term>Deferasirox</mesh_term>
  </intervention_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/NCT01718366
org study id: GFM-EXVD-AZA-2011-005623-41
nct id: NCT01718366
lead sponsor: 
collaborator: 
has dmc: Yes
Determinate safety and response rate of the association Deferasirox -Vitamine D - Azacitidine
      in treatment of high risk MDS

      Deferasirox Exjade:

      The dose of Deferasirox will be assigned according to the ferritin level. Dose escalation is
      scheduled during the phase I, with 5 additional patients per group.

      The maximal tolerated dose of Deferasirox will be required for the phase II of the study.

      The first dose will be assigned according to the ferritin level of the patient at time of
      inclusion:

      5 mg/kg/d if the ferritin is >300ng/ml and < 1000ng/ml in Group 1 10 mg/kg/d if the ferritin
      is ≥1000ng/ml) in Group 2

      Group 1 : Ferritin 300 to 1000ng /ml:

        -  cohort 1 : 5 mg/kg/d

        -  cohort 2 : 10mg/kg/d

        -  cohort 3 : 15 mg/kg/d

      Group 2 : Ferritin > 1000ng /ml:

        -  cohort 1 : 10 mg/kg/d

        -  cohort 2 : 15mg/kg/d

        -  cohort 3 : 20 mg/kg/d

           5 patients will be treated by cohort. In absence of toxicity (extra-hematological
           toxicity grade 3 or 4 or hematological grade 4), 5 additional patients will be included
           in the next cohort.

      Deferasirox will be administrated once daily during all the study period. Uvedose will be
      administrated once weekly during all the study period (100.000 UI P.O).

      Azacitidine will be administrated sc at 75 mg/m²/d, during 7 days, J1 to J7 of each
      cycles(One cycle is 28 days)

      During phase I and II, Deferasirox will always be associated with Vitamin D and Azacitidine

      Patients will be received 6 cycles of treatment (except if progression, unacceptable toxicity
      or withdrawn of patients occured) After 3 and 6 cycles, an evaluation will be done to
      evaluate the efficacy of the treatment.

      No dose modification of deferasirox will be done after 3 cycles of treatment except in case
      of progression). After 6 cycles, patients with CR, PR, marrow CR or HI will be treated with
      the same dose of Deferasirox until progression .
Deferasirox will be administrated once daily in the morning on an empty stomach, 30 minutes
      before meal.

      Deferasirox will be stopped if the ferritin level is under 100 ng/ml,and could be restarted
      is the ferritin level increase to 200 ng/ml

      Uvedose dose could be adjusted according to the phosphocalcic metabolism parameters and the
      plasma Vitamin D3 level.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: To determine the maximal tolerated dose(MTD
time frame: 6 month of treatment
description: patient will be evaluable after at least one cycle. Treatment will be administrated during 6 month and responders will be treated until progression or death
arm group label: ferritin level >300ng/ml and < 1000ng/ml
arm group type: Experimental
description: Patients will be included in 2 groups according to the ferritin level at time of inclusion.
Patients with the ferritin level >300ng/ml and < 1000ng/ml, will be included in Group 1.
Interventions: Deferasirox, Vitamin D (100000/week) and Azacitidine (75 mg/kg/day Day1 today 7)
5 patients in each cohort: Cohort 1: Deferasirox: 5mg/kg/d Cohort 2: Deferasirox: 10mg/kg/d Cohort 3: Deferasirox: 15mg/kg/d
arm group label: ferritin level > 1000ng/ml
arm group type: Experimental
description: Patients will be included in 2 groups according to the ferritin level at time of inclusion.
Patients with the ferritin level > 1000ng/ml, will be included in Group 2. Intervention: Deferasirox, Vitamin D (100000/week) and Azacitidine (75 mg/kg/day Day1 today 7)
5 patients in each cohort: Cohort 1: Deferasirox: 10mg/kg/d Cohort 2: Deferasirox: 15mg/kg/d Cohort 3: Deferasirox: 20mg/kg/d
intervention type: Drug
intervention name: Deferasirox, Vitamin D and Azacitidine
description: association of Deferasirox (group 1: 5-10-15/mg/kg/day according to dose level group), Vitamine D (100000U/week) and Azacitidine (75 mg/kg/day day1-day7)
arm group label: ferritin level > 1000ng/ml
arm group label: ferritin level >300ng/ml and < 1000ng/ml
other name: Exjade
other name: VitaminD
other name: Vidaza
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Olivier Hermine, MD
role: Principal Investigator
affiliation: Necker Hospital (Paris)
last name: Pierre Fenaux, MD
role: Study Director
affiliation: Saint Louis Hospital (Paris)
last name: Felipe Suarez, MD
role: Study Chair
affiliation: Necker Hospital (Paris)
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Belgium
country: France
responsible party type: Sponsor
mesh term: Vitamin D
mesh term: Azacitidine
mesh term: Deferasirox
sharing ipd: No