<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/NCT01709032</url>
  </required_header>
  <id_info>
    <org_study_id>12-009449</org_study_id>
    <nct_id>NCT01709032</nct_id>
  </id_info>
  <brief_title>Combination Deferasirox and Deferiprone for Severe Iron Overload in Thalassemia</brief_title>
  <official_title>Pilot Study of Deferasirox and Deferiprone Combination Oral Chelation for Individuals With Transfusion Dependent Thalassemia and High Iron Burden</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Children's Hospital of Philadelphia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The Cooley's Anemia Foundation,</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Ann &amp; Robert H Lurie Children's Hospital of Chicago</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Children's Hospital of Philadelphia</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      We hypothesize that the combination treatment with deferasirox and deferiprone will be well&#xD;
      tolerated and will result in significant improvement in cardiac and liver iron levels.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Death and disability from iron related damage to the heart remain the most serious issue&#xD;
      facing transfusion-dependent patients with thalassemia. However, over the past decade there&#xD;
      have been several reports of improved survival and fewer cardiac complications. This&#xD;
      improvement may be related to the availability of three chelators and also the accurate&#xD;
      measurement of iron stores in various organs (e.g. heart and liver) with magnetic resonance&#xD;
      imaging, which allows for personalized, tailored medical care for patients. The chelator&#xD;
      characteristics, side effect profiles, and ability to remove iron from specific organs differ&#xD;
      among the chelators, suggesting that combination therapy may be beneficial. Using two drugs&#xD;
      at lower doses may be more tolerable than escalating doses of a single drug and may improve&#xD;
      iron removal. The combination of deferoxamine and deferiprone has been shown to be&#xD;
      particularly beneficial for reducing cardiac iron, but it requires a painful&#xD;
      injection/infusion, which hinders adherence. This pilot study aims to investigate the safety&#xD;
      of an oral-only combination chelator regimen (deferasirox and deferiprone) in individuals&#xD;
      with thalassemia major with poorly controlled iron overload and to assess how well this&#xD;
      chelator combination lowers iron stores over one year.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 2012</start_date>
  <completion_date type="Actual">August 1, 2017</completion_date>
  <primary_completion_date type="Actual">August 1, 2015</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>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Improvement in Liver Iron Concentration</measure>
    <time_frame>12 months</time_frame>
    <description>Determine the safety of the combination of Deferasirox and Deferiprone for the treatment of subjects with Thalassemia Major and Severe Iron Overload by assessing change in liver iron concentration from baseline to follow-up</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Improvement in Cardiac T2* MRI</measure>
    <time_frame>12 months</time_frame>
    <description>Improvement in Cardiac T2* MRI from baseline to determine if there is a reduction of cardiac iron burden.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">9</enrollment>
  <condition>Thalassemia Major With Severe Transfusional Iron Overload</condition>
  <arm_group>
    <arm_group_label>Deferasirox and deferiprone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Deferasirox and deferiprone</intervention_name>
    <arm_group_label>Deferasirox and deferiprone</arm_group_label>
    <other_name>Exjade</other_name>
    <other_name>Ferriprox</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Alpha or beta thalassemia&#xD;
&#xD;
          -  Receiving chronic transfusions (at least 20 transfusions in lifetime) with iron&#xD;
             overload requiring treatment with chelation&#xD;
&#xD;
          -  Serum ferritin &gt;500 ng/ml&#xD;
&#xD;
          -  Liver iron concentration equal to or greater than 10 mg/g dw (by R2 MRI) or 7 to 10&#xD;
             mg/g dw (by R2 MRI) and not improving OR cardiac T2* between 6 and &lt;20 ms&#xD;
&#xD;
          -  Women of childbearing age must have a negative pregnancy test&#xD;
&#xD;
          -  Agree to use approved method of contraception for the duration of the study&#xD;
&#xD;
          -  Subjects must have a good understanding of the study and be willing to comply with&#xD;
             study procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with past history of unexplained neutropenia (ANC &lt; 1500/mcL), clinically&#xD;
             significant renal disease (creatinine above the upper limit of normal), proteinuria&#xD;
             &gt;300 mg/L, clinically significant liver disease (ALT &gt; 5x upper limit of normal),&#xD;
             pulmonary or cardiovascular disease&#xD;
&#xD;
          -  History of other clinically relevant oral, endocrine, neurologic, psychiatric,&#xD;
             immunologic, bone marrow or skin disorder that contraindicates dosing with deferasirox&#xD;
             or deferiprone&#xD;
&#xD;
          -  History of adverse reaction or known allergy to either deferasirox or deferiprone&#xD;
             necessitating drug discontinuation&#xD;
&#xD;
          -  Currently receiving treatment for active hepatitis&#xD;
&#xD;
          -  Use of any investigational agent in the past 30 days&#xD;
&#xD;
          -  Cardiac T2* &lt;6 ms, left ventricular ejection fraction &lt; 56%, and/or arrhythmia&#xD;
             (certain subjects may be eligible if they have already had a trial of deferoxamine and&#xD;
             deferiprone). Subjects who refuse to use deferoxamine after extensive consultation&#xD;
             with at least 2 health care providers will also be allowed to participate.&#xD;
&#xD;
          -  Pregnant or breastfeeding females&#xD;
&#xD;
          -  Unwilling or unable to comply with study related procedures&#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>Janet L Kwiatkowski, MD, MSCE</last_name>
    <role>Principal Investigator</role>
    <affiliation>Children's Hospital of Philadlephia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Ann &amp; Robert H. Lurie Children's Hospital of Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Philadelphia</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Canada</country>
  </removed_countries>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>October 16, 2012</study_first_submitted>
  <study_first_submitted_qc>October 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 17, 2012</study_first_posted>
  <results_first_submitted>August 1, 2017</results_first_submitted>
  <results_first_submitted_qc>February 13, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">March 6, 2019</results_first_posted>
  <last_update_submitted>February 13, 2019</last_update_submitted>
  <last_update_submitted_qc>February 13, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 6, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Thalassemia</keyword>
  <keyword>Chelation</keyword>
  <keyword>Transfusion</keyword>
  <keyword>Safety</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thalassemia</mesh_term>
    <mesh_term>beta-Thalassemia</mesh_term>
    <mesh_term>Iron Overload</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Deferasirox</mesh_term>
    <mesh_term>Deferiprone</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Deferasirox and Deferiprone</title>
          <description>Deferasirox and deferiprone</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Deferasirox and Deferiprone</title>
          <description>Deferasirox and deferiprone</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="9"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="28.9" spread="5.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Improvement in Liver Iron Concentration</title>
        <description>Determine the safety of the combination of Deferasirox and Deferiprone for the treatment of subjects with Thalassemia Major and Severe Iron Overload by assessing change in liver iron concentration from baseline to follow-up</description>
        <time_frame>12 months</time_frame>
        <population>Number with participants with improvement in liver iron concentration</population>
        <group_list>
          <group group_id="O1">
            <title>Deferasirox and Deferiprone</title>
            <description>Deferasirox and deferiprone</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Improvement in Liver Iron Concentration</title>
          <description>Determine the safety of the combination of Deferasirox and Deferiprone for the treatment of subjects with Thalassemia Major and Severe Iron Overload by assessing change in liver iron concentration from baseline to follow-up</description>
          <population>Number with participants with improvement in liver iron concentration</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Improvement in Cardiac T2* MRI</title>
        <description>Improvement in Cardiac T2* MRI from baseline to determine if there is a reduction of cardiac iron burden.</description>
        <time_frame>12 months</time_frame>
        <population>Number of participants with improvement</population>
        <group_list>
          <group group_id="O1">
            <title>Deferasirox and Deferiprone Combination Chelation</title>
            <description>Deferasirox and deferiprone</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Improvement in Cardiac T2* MRI</title>
          <description>Improvement in Cardiac T2* MRI from baseline to determine if there is a reduction of cardiac iron burden.</description>
          <population>Number of participants with improvement</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Deferasirox and Deferiprone</title>
          <description>Deferasirox and deferiprone</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Rectal bleeding from hemorrhoid</sub_title>
                <description>unrelated to study treatment</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>viral syndrome</sub_title>
                <description>Admitted with fever and abdominal pain thought unrelated to study treatment</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>perirectal abscess</sub_title>
                <description>Unrelated to study drug</description>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Tinnitus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Nausea/vomiting</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>ALT elevated</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="7" subjects_affected="4" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Janet Kwiatkowski, MD</name_or_title>
      <organization>Children's Hospital of Philadelphia</organization>
      <phone>215-590-3437</phone>
      <email>kwiatkowski@email.chop.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01709032
org study id: 12-009449
nct id: NCT01709032
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
We hypothesize that the combination treatment with deferasirox and deferiprone will be well
      tolerated and will result in significant improvement in cardiac and liver iron levels.
Death and disability from iron related damage to the heart remain the most serious issue
      facing transfusion-dependent patients with thalassemia. However, over the past decade there
      have been several reports of improved survival and fewer cardiac complications. This
      improvement may be related to the availability of three chelators and also the accurate
      measurement of iron stores in various organs (e.g. heart and liver) with magnetic resonance
      imaging, which allows for personalized, tailored medical care for patients. The chelator
      characteristics, side effect profiles, and ability to remove iron from specific organs differ
      among the chelators, suggesting that combination therapy may be beneficial. Using two drugs
      at lower doses may be more tolerable than escalating doses of a single drug and may improve
      iron removal. The combination of deferoxamine and deferiprone has been shown to be
      particularly beneficial for reducing cardiac iron, but it requires a painful
      injection/infusion, which hinders adherence. This pilot study aims to investigate the safety
      of an oral-only combination chelator regimen (deferasirox and deferiprone) in individuals
      with thalassemia major with poorly controlled iron overload and to assess how well this
      chelator combination lowers iron stores over one year.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With Improvement in Liver Iron Concentration
time frame: 12 months
description: Determine the safety of the combination of Deferasirox and Deferiprone for the treatment of subjects with Thalassemia Major and Severe Iron Overload by assessing change in liver iron concentration from baseline to follow-up
measure: Number of Participants With Improvement in Cardiac T2* MRI
time frame: 12 months
description: Improvement in Cardiac T2* MRI from baseline to determine if there is a reduction of cardiac iron burden.
arm group label: Deferasirox and deferiprone
arm group type: Experimental
intervention type: Drug
intervention name: Deferasirox and deferiprone
arm group label: Deferasirox and deferiprone
other name: Exjade
other name: Ferriprox
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Janet L Kwiatkowski, MD, MSCE
role: Principal Investigator
affiliation: Children's Hospital of Philadlephia
facility: 
facility: 
country: United States
country: Canada
responsible party type: Sponsor
mesh term: Thalassemia
mesh term: beta-Thalassemia
mesh term: Iron Overload
mesh term: Deferasirox
mesh term: Deferiprone
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 