<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/NCT01698879</url>
  </required_header>
  <id_info>
    <org_study_id>ICOG-07</org_study_id>
    <secondary_id>2007-006295-11</secondary_id>
    <nct_id>NCT01698879</nct_id>
  </id_info>
  <brief_title>Prospective Study of Mylotarg and G-CSF in Acute Myeloid Leukemia Treatment</brief_title>
  <official_title>Treatment of de Novo Acute Myeloid Leukemia With the Combination of Idarubicin, Cytarabine, and Gemtuzumab Ozogamicin (Mylotarg ®), Associated or Not Priming With G-CSF. Prospective Study of Efficacy and Toxicity</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Acute myeloid leukemia (AML) is a neoplasm of immature hematopoietic cells (blasts) with&#xD;
      altered ripening capacity. Due to excessive proliferation, the blasts displace normal&#xD;
      hematopoietic cells and bone marrow failure appears. Leukemic cells also infiltrate&#xD;
      extramedullary tissues.&#xD;
&#xD;
      Following the standard chemotherapy treatment, the CR rate achieved is around 65-75% for all&#xD;
      patients and 15% lower when considering only patients over 65 years. Modifications to the&#xD;
      standard regimen consist of replacing the DNR for a cytotoxic one, modifying the dose of&#xD;
      ara-C or adding a third drug.&#xD;
&#xD;
      Gemtuzumab ozogamicin (Mylotarg ®) is an immunoconjugate between anti-CD33 antibody and a&#xD;
      cytotoxic antitumor antibiotic, calicheamicin. Mylotarg ® antibody specifically binds to&#xD;
      CD33, a sialic acid-dependent adhesion protein expressed in over 90% of LMA10. Mylotarg ®&#xD;
      selectively transports the cytotoxic agent calicheamicin into leukemic cells and&#xD;
      hematopoietic progenitors differentiated from the myelomonocytic line, while respecting the&#xD;
      pluripotent hematopoietic stem cells. Calicheamicin is released only after the fixation of&#xD;
      the antibody anti-CD33 and its internalization by the cell, after which binds to and damages&#xD;
      the DNA.&#xD;
&#xD;
      Mylotarg ® is approved in the U.S. for the treatment of CD33 positive AML in first relapse,&#xD;
      for patients older than 60 years non-candidates for other intensive treatment modalities.&#xD;
&#xD;
      Since the efficacy of Mylotarg ® is equivalent and its toxicity profile less than the&#xD;
      conventional therapy, it is logical to conduct a phase II trial exploring the role of&#xD;
      Mylotarg ® in the early stages of treatment of AML.&#xD;
&#xD;
      Previous experience with gemtuzumab ozogamicin in relapsed patients led to its use combined&#xD;
      with induction chemotherapy. The aim was to improve the CR rate reached with the latter and&#xD;
      reduce relapse after achieving greater leukemic cytoreduction.&#xD;
&#xD;
      Recent data from the HOVON group support that the administration of G-CSF before and during&#xD;
      induction chemotherapy decreases the incidence of relapse in patients with AML, particularly&#xD;
      those considered to have intermediate risk.&#xD;
&#xD;
      Everything mentioned above justifies to investigate the combination of GO combined with&#xD;
      chemotherapy with IDR and ara-C in standard 3x7 scheme and analyze the effect of&#xD;
      sensitization with G-CSF in patients with AML de novo. If the treatment proposed here is&#xD;
      effective and presents an acceptable toxicity it should be investigated.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>October 2009</start_date>
  <completion_date type="Actual">September 26, 2016</completion_date>
  <primary_completion_date type="Actual">September 14, 2016</primary_completion_date>
  <phase>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>Complete Remission of the Disease</measure>
    <time_frame>28 days after chemotherapy</time_frame>
    <description>Rate of patients that have obtained complete remission. Complete remission is defined as, bone marrow normocellular or slightly hypocellular with proportion of blasts &lt;5%, including the erythroid cell count (and including promonocytes in case of M5), no Auer rods, no extramedullary leukemia, neutrophils and platelets rising. The persistence of minimal residual disease in immunophenotypic study will not invalidate the standard cytogenetic complete remission.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Secondary Toxicity to Mylotarg(R)</measure>
    <time_frame>Baseline, weekly during treatment and at month 3 and month 6 after first induction.</time_frame>
    <description>Hematological toxicity, hepatic and gastrointestinal toxicity, fever and infections, pulmonary complications, duration of hospitalization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality at Induction</measure>
    <time_frame>Weekly during treatment, at third month and at 6 months after last administration of Mylotarg</time_frame>
    <description>all deaths occurring after the first administration of MylotargTM until the time of transplantation with no leukemic relapse has occurred, and all deaths in the 6 first months after administration of the second dose of MylotargTM with no leukemic relapse occurred.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Capacity to Obtain Hematopoietic Progenitor Cells (HPC) for Autotransplantation - DATA NOT COLLECTED</measure>
    <time_frame>One month before transplant, expected at 9 months after end of treatment.</time_frame>
    <description>Rate of patients with capacity to obtain hematopoietic progenitor cells (HPC) for autotransplantation. This analysis has not been performed, because data were not available in sites.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relapse After 6 Months</measure>
    <time_frame>6 months from complete remission</time_frame>
    <description>Rate of patients that have relapse after 6 months of obtained complete remission.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Survival After 6 Months</measure>
    <time_frame>6 months after complete remission</time_frame>
    <description>rate of patients alive within 6 months of obtained complete remission</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">46</enrollment>
  <condition>Novo Acute Myeloid Leukemia</condition>
  <arm_group>
    <arm_group_label>Single arm, three cohorts</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Idarubicin, cytarabine, Mylotarg.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mylotarg</intervention_name>
    <description>Cohort 1 version 1.0. GO: 6mg/m^2 (maximum 10 mg), IV infusion, 2 hours, day 1. Idarubicin: 12 mg/m^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine: 100 mg/m^2 IV days 1 to 7, to begin 4 hours after the administration of GO.&#xD;
Cohort 1.0 version 2.0: GO: 3 mg/m^2 (maximum 5 mg), IV infusion, 2 hours, day 1. Idarubicin: 12 mg/m^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine: 100 mg/m^2 IV days 1 to 7, to begin 4 hours after the administration of GO.&#xD;
Cohort 2: G-CSF: 150 mcg/m^2, SC, days 0 to 7. GO: 3 mg/m^2 (maximum 5 mg), IV infusion, 2 hours, day 1. Idarubicin: 12 mg/m^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine: 100 mg/m^2 IV continuous infusion on days 1 to 7, to begin 4 hours later after the administration of GO.</description>
    <arm_group_label>Single arm, three cohorts</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients with primary or &quot;de novo&quot; AML, different than promyelocytic or M3 subtype.&#xD;
&#xD;
          2. Age 18 to 70 years.&#xD;
&#xD;
          3. Written informed consent form&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Acute leukemia appeared after a myeloproliferative process or a myelodysplastic&#xD;
             syndrome longer than 6 months, AML arising after another cured malignant disease (e.g.&#xD;
             Hodgkin's disease), and secondary AML treated with alkylating agents or radiation.&#xD;
&#xD;
          2. Acute promyelocytic leukemia.&#xD;
&#xD;
          3. Relevant history of liver disease. Significant impaired liver function (bilirubin, AST&#xD;
             or ALT ≥ 2.5 times the normal value) not attributable to leukemic infiltration.&#xD;
&#xD;
          4. Patients with prior heart failure.&#xD;
&#xD;
          5. Symptomatic chronic respiratory failure.&#xD;
&#xD;
          6. Positive serology for HIV, hepatitis C virus or its surface antigen.&#xD;
&#xD;
          7. Estimated life expectancy less than 3 months, despite treatment.&#xD;
&#xD;
          8. Pregnancy or breastfeeding at the time of inclusion in the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jordi Sierra, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital Germans Trias i Pujol</name>
      <address>
        <city>Badalona</city>
        <state>Barcelona</state>
        <zip>08916</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de la Santa Creu i Sant Pau</name>
      <address>
        <city>Barcelona</city>
        <zip>08025</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinic Barcelona</name>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinico Universitario de Salamanca</name>
      <address>
        <city>Salamanca</city>
        <zip>37007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen del Rocio</name>
      <address>
        <city>Sevilla</city>
        <zip>41013</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clínico Universitario de Valencia</name>
      <address>
        <city>Valencia</city>
        <zip>496010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>July 23, 2012</study_first_submitted>
  <study_first_submitted_qc>October 1, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 3, 2012</study_first_posted>
  <results_first_submitted>February 13, 2017</results_first_submitted>
  <results_first_submitted_qc>January 26, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">January 27, 2021</results_first_posted>
  <last_update_submitted>January 26, 2021</last_update_submitted>
  <last_update_submitted_qc>January 26, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 27, 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>Leukemia</mesh_term>
    <mesh_term>Leukemia, Myeloid</mesh_term>
    <mesh_term>Leukemia, Myeloid, Acute</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gemtuzumab</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Cohort 1 Version 1.0</title>
          <description>Mylotarg: Cohort 1 version 1.0 (5 evaluable patients):&#xD;
GO: 6 mg/m^2 (maximum 10 mg), IV infusion, 2 hours, day 1. Idarubicin: 12 mg/m^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine (cytosine arabinoside): 100 mg/m^2 IV continuous infusion on days 1 to 7, to begin 4 hours after the administration of GO.&#xD;
If chemo-sensitivity is observed after a first course of treatment (50% or more reduction of blasts compared to baseline) a second identical cycle will be administered.</description>
        </group>
        <group group_id="P2">
          <title>Cohort 1 Version 2.0</title>
          <description>Idarubicin, cytarabine, Mylotarg&#xD;
Mylotarg: Cohort 1 (20 evaluable patients):&#xD;
GO: 3 mg/m^2 (maximum 5 mg), IV infusion, 2 hours, day 1. Idarubicin: 12 mg/m^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine (cytosine arabinoside): 100 mg/m^2 IV continuous infusion on days 1 to 7, to begin 4 hours after the administration of GO.</description>
        </group>
        <group group_id="P3">
          <title>Cohort 2</title>
          <description>Cohort 2 (20 evaluable patients):&#xD;
G-CSF: 150 mcg/m^2, SC, days 0 to 7, to begin 12 to 18 hours before treatment with Gemtuzumab. GO: 3 mg/m^2 (maximum 5 mg), IV infusion, 2 hours, day 1.&#xD;
Idarubicin: 12 mg/m^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine (cytosine arabinoside): 100 mg/m^2 IV continuous infusion on days 1 to 7, to begin 4 hours later after the administration of GO.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="20"/>
                <participants group_id="P3" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="20"/>
                <participants group_id="P3" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>From cohort 1 version 1.0, one patient did not receive any study treatment (PIS withdrawal), for that reason is not considered for outcome assessment.</population>
      <group_list>
        <group group_id="B1">
          <title>Cohort 1, Version 1.0</title>
          <description>Mylotarg: Cohort 1 version 1.0 (5 evaluable patients):&#xD;
GO: 6 mg/m^2 (maximum 10 mg), IV infusion, 2 hours, day 1. Idarubicin: 12 mg/m^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine (cytosine arabinoside): 100 mg/m^2 IV continuous infusion on days 1 to 7, to begin 4 hours after the administration of GO.&#xD;
If chemo-sensitivity is observed after a first course of treatment (50% or more reduction of blasts compared to baseline) a second identical cycle will be administered.</description>
        </group>
        <group group_id="B2">
          <title>Cohort 1, Version 2.0</title>
          <description>Mylotarg: Cohort 1 (20 evaluable patients):&#xD;
GO: 3 mg/m^2 (maximum 5 mg), IV infusion, 2 hours, day 1. Idarubicin: 12 mg/m^2, IV, 30 minutes, on days 2, 3, 4.&#xD;
Cytarabine (cytosine arabinoside): 100 mg/m^2 IV continuous infusion on days 1 to 7, to begin 4 hours after the administration of GO.</description>
        </group>
        <group group_id="B3">
          <title>Cohort 2</title>
          <description>Cohort 2 (20 evaluable patients):&#xD;
G-CSF: 150 mcg/m^2, SC, days 0 to 7, to begin 12 to 18 hours before treatment with Gemtuzumab. GO: 3 mg/m^2 (maximum 5 mg), IV infusion, 2 hours, day 1.&#xD;
Idarubicin: 12 mg/m^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine (cytosine arabinoside): 100 mg/m^2 IV continuous infusion on days 1 to 7, to begin 4 hours later after the administration of GO.</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="5"/>
            <count group_id="B2" value="20"/>
            <count group_id="B3" value="20"/>
            <count group_id="B4" value="45"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="56" lower_limit="32" upper_limit="61"/>
                    <measurement group_id="B2" value="49" lower_limit="22" upper_limit="64"/>
                    <measurement group_id="B3" value="61" lower_limit="24" upper_limit="69"/>
                    <measurement group_id="B4" value="61" lower_limit="22" upper_limit="69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <population>The first 5 patients received GO 6mg/m2 but this dose was halted by unacceptable toxicity. Therefore, in Cohort 1 were included 20 patients receiving IA plus 3 mg/m2 GO. Cohort 2 included 20 patients who received treatment as in cohort 1 plus G-CSF priming</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="15"/>
                    <measurement group_id="B4" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <population>One patient has not been evaluated because has not received study treatment.</population>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Spain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="20"/>
                    <measurement group_id="B4" value="45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Leucocites at diagnosis</title>
          <population>The first 5 patients received GO 6mg/m2 but this dose was halted by unacceptable toxicity. Therefore, in Cohort 1 were included 20 patients receiving IA plus 3 mg/m2 GO. Cohort 2 included 20 patients who received treatment as in cohort 1 plus G-CSF priming.</population>
          <units>Cells x 10^9/L</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="13.48" lower_limit="2.1" upper_limit="31.85"/>
                    <measurement group_id="B2" value="7.66" lower_limit="1" upper_limit="96.6"/>
                    <measurement group_id="B3" value="6.96" lower_limit="0.9" upper_limit="114"/>
                    <measurement group_id="B4" value="6.96" lower_limit="0.9" upper_limit="114"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Citogenetic</title>
          <population>1 patient not evaluable because has not received study treatment.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Favorable</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Intermediate</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="12"/>
                    <measurement group_id="B4" value="28"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Adverse</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Complete Remission of the Disease</title>
        <description>Rate of patients that have obtained complete remission. Complete remission is defined as, bone marrow normocellular or slightly hypocellular with proportion of blasts &lt;5%, including the erythroid cell count (and including promonocytes in case of M5), no Auer rods, no extramedullary leukemia, neutrophils and platelets rising. The persistence of minimal residual disease in immunophenotypic study will not invalidate the standard cytogenetic complete remission.</description>
        <time_frame>28 days after chemotherapy</time_frame>
        <population>Initial 5 patients included in cohort 1 version 1.0 (closed due toxicity) have been evaluated for safety outcome but not evaluated for efficacy because the treatment is not feasible.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1, Version 1.0</title>
            <description>Mylotarg: Cohort 1 version 1.0 (5 evaluable patients):&#xD;
GO: 6 mg/m^2 (maximum 10 mg), IV infusion, 2 hours, day 1. Idarubicin: 12 mg/m^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine (cytosine arabinoside): 100 mg/m^2 IV continuous infusion on days 1 to 7, to begin 4 hours after the administration of GO.&#xD;
If chemo-sensitivity is observed after a first course of treatment (50% or more reduction of blasts compared to baseline) a second identical cycle will be administered.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 1, Version 2.0</title>
            <description>Mylotarg: Cohort 1 (20 evaluable patients):&#xD;
GO: 3 mg/m^2 (maximum 5 mg), IV infusion, 2 hours, day 1. Idarubicin: 12 mg/m^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine (cytosine arabinoside): 100 mg/m^2 IV continuous infusion on days 1 to 7, to begin 4 hours after the administration of GO.</description>
          </group>
          <group group_id="O3">
            <title>Cohort 2</title>
            <description>Cohort 2 (20 evaluable patients):&#xD;
G-CSF: 150 mcg/m^2, SC, days 0 to 7, to begin 12 to 18 hours before treatment with Gemtuzumab. GO: 3 mg/m^2 (maximum 5 mg), IV infusion, 2 hours, day 1.&#xD;
Idarubicin: 12 mg/m^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine (cytosine arabinoside): 100 mg/m^2 IV continuous infusion on days 1 to 7, to begin 4 hours later after the administration of GO.</description>
          </group>
        </group_list>
        <measure>
          <title>Complete Remission of the Disease</title>
          <description>Rate of patients that have obtained complete remission. Complete remission is defined as, bone marrow normocellular or slightly hypocellular with proportion of blasts &lt;5%, including the erythroid cell count (and including promonocytes in case of M5), no Auer rods, no extramedullary leukemia, neutrophils and platelets rising. The persistence of minimal residual disease in immunophenotypic study will not invalidate the standard cytogenetic complete remission.</description>
          <population>Initial 5 patients included in cohort 1 version 1.0 (closed due toxicity) have been evaluated for safety outcome but not evaluated for efficacy because the treatment is not feasible.</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="5"/>
                <count group_id="O2" value="20"/>
                <count group_id="O3" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Complete Response</title>
                  <measurement_list>
                    <measurement group_id="O1" value="NA">It has not been evaluated efficacy result of this cohort with unacceptable toxicity profile</measurement>
                    <measurement group_id="O2" value="18"/>
                    <measurement group_id="O3" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Partial Response</title>
                  <measurement_list>
                    <measurement group_id="O1" value="NA">It has not been evaluated efficacy result of this cohort with unacceptable toxicity profile</measurement>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Refractory</title>
                  <measurement_list>
                    <measurement group_id="O1" value="NA">It has not been evaluated efficacy result of this cohort with unacceptable toxicity profile</measurement>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Toxicity to Mylotarg(R)</title>
        <description>Hematological toxicity, hepatic and gastrointestinal toxicity, fever and infections, pulmonary complications, duration of hospitalization</description>
        <time_frame>Baseline, weekly during treatment and at month 3 and month 6 after first induction.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1, Version 1.0</title>
            <description>Initial 5 patients of cohort 1 (closed due toxicity)</description>
          </group>
          <group group_id="O2">
            <title>Cohort 1, Version 2.0</title>
            <description>Idarubicin, cytarabine, Mylotarg&#xD;
Mylotarg: Cohort 1 (20 evaluable patients):&#xD;
GO: 3 mg/m^2 (maximum 5 mg), IV infusion, 2 hours, day 1. Idarubicin: 12 mg/m^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine (cytosine arabinoside): 100 mg/m^2 IV continuous infusion on days 1 to 7, to begin 4 hours after the administration of GO.</description>
          </group>
          <group group_id="O3">
            <title>Cohort 2</title>
            <description>Cohort 2 (20 evaluable patients):&#xD;
G-CSF: 150 mcg/m^2, SC, days 0 to 7, to begin 12 to 18 hours before treatment with Gemtuzumab. GO: 3 mg/m^2 (maximum 5 mg), IV infusion, 2 hours, day 1.&#xD;
Idarubicin: 12 mg/m^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine (cytosine arabinoside): 100 mg/m^2 IV continuous infusion on days 1 to 7, to begin 4 hours later after the administration of GO.</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Toxicity to Mylotarg(R)</title>
          <description>Hematological toxicity, hepatic and gastrointestinal toxicity, fever and infections, pulmonary complications, duration of hospitalization</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="20"/>
                <count group_id="O3" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Grade IV Hematologic toxicity</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="100"/>
                    <measurement group_id="O3" value="95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade II Hematologic toxicity</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade I/II Hepatic toxicity</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                    <measurement group_id="O2" value="10"/>
                    <measurement group_id="O3" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade III/IV hepatic toxicity</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40"/>
                    <measurement group_id="O2" value="5"/>
                    <measurement group_id="O3" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade I/II Infection</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="10"/>
                    <measurement group_id="O3" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade III/IV Infection</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="5"/>
                    <measurement group_id="O3" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mortality at Induction</title>
        <description>all deaths occurring after the first administration of MylotargTM until the time of transplantation with no leukemic relapse has occurred, and all deaths in the 6 first months after administration of the second dose of MylotargTM with no leukemic relapse occurred.</description>
        <time_frame>Weekly during treatment, at third month and at 6 months after last administration of Mylotarg</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1, Version 1.0</title>
            <description>Initial 5 patients of cohort 1 (closed due toxicity)</description>
          </group>
          <group group_id="O2">
            <title>Cohort 1 Version 2.0</title>
            <description>Mylotarg: Cohort 1 (20 evaluable patients):&#xD;
GO: 3 mg/m^2 (maximum 5 mg), IV infusion, 2 hours, day 1. Idarubicin: 12 mg/m^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine (cytosine arabinoside): 100 mg/m^2 IV continuous infusion on days 1 to 7, to begin 4 hours after the administration of GO.</description>
          </group>
          <group group_id="O3">
            <title>Cohort 2</title>
            <description>Cohort 2 (20 evaluable patients):&#xD;
G-CSF: 150 mcg/m^2, SC, days 0 to 7, to begin 12 to 18 hours before treatment with Gemtuzumab. GO: 3 mg/m^2 (maximum 5 mg), IV infusion, 2 hours, day 1.&#xD;
Idarubicin: 12 mg/m^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine (cytosine arabinoside): 100 mg/m^2 IV continuous infusion on days 1 to 7, to begin 4 hours later after the administration of GO.</description>
          </group>
        </group_list>
        <measure>
          <title>Mortality at Induction</title>
          <description>all deaths occurring after the first administration of MylotargTM until the time of transplantation with no leukemic relapse has occurred, and all deaths in the 6 first months after administration of the second dose of MylotargTM with no leukemic relapse occurred.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="20"/>
                <count group_id="O3" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Capacity to Obtain Hematopoietic Progenitor Cells (HPC) for Autotransplantation - DATA NOT COLLECTED</title>
        <description>Rate of patients with capacity to obtain hematopoietic progenitor cells (HPC) for autotransplantation. This analysis has not been performed, because data were not available in sites.</description>
        <time_frame>One month before transplant, expected at 9 months after end of treatment.</time_frame>
        <population>Initial 5 patients included in cohort 1 version 1.0 (closed due toxicity) have been evaluated for safety outcome but not evaluated for efficacy because the treatment is not feasible. This analysis has not been performed because data were not available for any of the cohorts studied.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1, Version 1.0</title>
            <description>Mylotarg: Cohort 1 version 1.0 (5 evaluable patients):&#xD;
GO: 6 mg/m^2 (maximum 10 mg), IV infusion, 2 hours, day 1. Idarubicin: 12 mg/m^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine (cytosine arabinoside): 100 mg/m^2 IV continuous infusion on days 1 to 7, to begin 4 hours after the administration of GO.&#xD;
If chemo-sensitivity is observed after a first course of treatment (50% or more reduction of blasts compared to baseline) a second identical cycle will be administered.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 1, Version 2.0</title>
            <description>Idarubicin, cytarabine, Mylotarg&#xD;
Mylotarg: Cohort 1 (20 evaluable patients):&#xD;
GO: 3 mg/m^2 (maximum 5 mg), IV infusion, 2 hours, day 1. Idarubicin: 12 mg/m^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine (cytosine arabinoside): 100 mg/m^2 IV continuous infusion on days 1 to 7, to begin 4 hours after the administration of GO.</description>
          </group>
          <group group_id="O3">
            <title>Cohort 2</title>
            <description>Cohort 2 (20 evaluable patients):&#xD;
G-CSF: 150 mcg/m^2, SC, days 0 to 7, to begin 12 to 18 hours before treatment with Gemtuzumab. GO: 3 mg/m^2 (maximum 5 mg), IV infusion, 2 hours, day 1.&#xD;
Idarubicin: 12 mg/m^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine (cytosine arabinoside): 100 mg/m^2 IV continuous infusion on days 1 to 7, to begin 4 hours later after the administration of GO.</description>
          </group>
        </group_list>
        <measure>
          <title>Capacity to Obtain Hematopoietic Progenitor Cells (HPC) for Autotransplantation - DATA NOT COLLECTED</title>
          <description>Rate of patients with capacity to obtain hematopoietic progenitor cells (HPC) for autotransplantation. This analysis has not been performed, because data were not available in sites.</description>
          <population>Initial 5 patients included in cohort 1 version 1.0 (closed due toxicity) have been evaluated for safety outcome but not evaluated for efficacy because the treatment is not feasible. This analysis has not been performed because data were not available for any of the cohorts studied.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Relapse After 6 Months</title>
        <description>Rate of patients that have relapse after 6 months of obtained complete remission.</description>
        <time_frame>6 months from complete remission</time_frame>
        <population>Initial 5 patients included in cohort 1 version 1.0 (closed due toxicity) have been evaluated for safety outcome but not evaluated for efficacy because the treatment is not feasible.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1, Version 2.0</title>
            <description>Idarubicin, cytarabine, Mylotarg.&#xD;
Mylotarg: Cohort 1 (20 evaluable patients):&#xD;
GO: 3 mg/m^2 (maximum 5 mg), IV infusion, 2 hours, day 1. Idarubicin: 12 mg/m^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine (cytosine arabinoside): 100 mg/m^2 IV continuous infusion on days 1 to 7, to begin 4 hours after the administration of GO.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2</title>
            <description>Cohort 2 (20 evaluable patients):&#xD;
G-CSF: 150 mcg/m^2, SC, days 0 to 7, to begin 12 to 18 hours before treatment with Gemtuzumab. GO: 3 mg/m^2 (maximum 5 mg), IV infusion, 2 hours, day 1.&#xD;
Idarubicin: 12 mg/m^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine (cytosine arabinoside): 100 mg/m^2 IV continuous infusion on days 1 to 7, to begin 4 hours later after the administration of GO.</description>
          </group>
        </group_list>
        <measure>
          <title>Relapse After 6 Months</title>
          <description>Rate of patients that have relapse after 6 months of obtained complete remission.</description>
          <population>Initial 5 patients included in cohort 1 version 1.0 (closed due toxicity) have been evaluated for safety outcome but not evaluated for efficacy because the treatment is not feasible.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30"/>
                    <measurement group_id="O2" value="59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Survival After 6 Months</title>
        <description>rate of patients alive within 6 months of obtained complete remission</description>
        <time_frame>6 months after complete remission</time_frame>
        <population>Initial 5 patients included in cohort 1 version 1.0 (closed due toxicity) have been evaluated for safety outcome but not evaluated for efficacy because the treatment is not feasible.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1</title>
            <description>Idarubicin, cytarabine, Mylotarg, G-CSF.&#xD;
Mylotarg: Cohort 1 (20 evaluable patients):&#xD;
GO: 3 mg/m^2 (maximum 5 mg), IV infusion, 2 hours, day 1. Idarubicin: 12 mg/m^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine (cytosine arabinoside): 100 mg/m^2 IV continuous infusion on days 1 to 7, to begin 4 hours after the administration of GO.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2</title>
            <description>Cohort 2 (20 evaluable patients):&#xD;
G-CSF: 150 mcg/m^2, SC, days 0 to 7, to begin 12 to 18 hours before treatment with Gemtuzumab. GO: 3 mg/m^2 (maximum 5 mg), IV infusion, 2 hours, day 1.&#xD;
Idarubicin: 12 mg/m^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine (cytosine arabinoside): 100 mg/m^2 IV continuous infusion on days 1 to 7, to begin 4 hours later after the administration of GO.</description>
          </group>
        </group_list>
        <measure>
          <title>Survival After 6 Months</title>
          <description>rate of patients alive within 6 months of obtained complete remission</description>
          <population>Initial 5 patients included in cohort 1 version 1.0 (closed due toxicity) have been evaluated for safety outcome but not evaluated for efficacy because the treatment is not feasible.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="80"/>
                    <measurement group_id="O2" value="80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From October 2008 up to September 2016, 7 years and 11 months.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Cohort 1</title>
          <description>Idarubicin, cytarabine, Mylotarg, G-CSF.&#xD;
Mylotarg: Cohort 1 (20 evaluable patients):&#xD;
GO: 3 mg/m^2 (maximum 5 mg), IV infusion, 2 hours, day 1. Idarubicin: 12 mg/m^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine (cytosine arabinoside): 100 mg/m^2 IV continuous infusion on days 1 to 7, to begin 4 hours after the administration of GO.</description>
        </group>
        <group group_id="E2">
          <title>Cohort 2</title>
          <description>Cohort 2 (20 evaluable patients):&#xD;
G-CSF: 150 mcg/m^2, SC, days 0 to 7, to begin 12 to 18 hours before treatment with Gemtuzumab. GO: 3 mg/m^2 (maximum 5 mg), IV infusion, 2 hours, day 1.&#xD;
Idarubicin: 12 mg/m^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine (cytosine arabinoside): 100 mg/m^2 IV continuous infusion on days 1 to 7, to begin 4 hours later after the administration of GO.</description>
        </group>
        <group group_id="E3">
          <title>5 Patients Treated in Trial With Prrotocol Version 1.0</title>
          <description>Idarubicin, cytarabine, Mylotarg, G-CSF.&#xD;
Mylotarg::&#xD;
GO: 5 mg/m^2 (maximum 10 mg), IV infusion, 2 hours, day 1. If no adequate response, GO: 3 mg/m^2 (maximum 5 mg), IV infusion, 2 hours, day 1.&#xD;
Idarubicin: 12 mg/m^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine (cytosine arabinoside): 100 mg/m^2 IV continuous infusion on days 1 to 7, to begin 4 hours after the administration of GO.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>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="1" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="20"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Liver failure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Hepatic Toxicity</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Septic shock</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Toxic megacolon</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Transient Ischemic event</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Severe respiratory failure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Bilateral pneumonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Acute Pulmonary Edema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </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="20" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="20"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Grade 4 hematologic toxicity</sub_title>
                <counts group_id="E1" events="20" subjects_affected="20" subjects_at_risk="20"/>
                <counts group_id="E2" events="19" subjects_affected="19" subjects_at_risk="20"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>G1/2 Hepatic toxicity</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>G3/G4 Hepatic Toxicity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="20"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Grade I/II infectous toxicity</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="20"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Grade 3 Infectous toxicity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="20"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Jordi Sierra</name_or_title>
      <organization>CETLAM</organization>
      <phone>+34 93 434 44 12</phone>
      <email>jsierra@santpau.cat</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/NCT01698879
org study id: ICOG-07
secondary id: 2007-006295-11
nct id: NCT01698879
lead sponsor: 
has dmc: No
Acute myeloid leukemia (AML) is a neoplasm of immature hematopoietic cells (blasts) with
      altered ripening capacity. Due to excessive proliferation, the blasts displace normal
      hematopoietic cells and bone marrow failure appears. Leukemic cells also infiltrate
      extramedullary tissues.

      Following the standard chemotherapy treatment, the CR rate achieved is around 65-75% for all
      patients and 15% lower when considering only patients over 65 years. Modifications to the
      standard regimen consist of replacing the DNR for a cytotoxic one, modifying the dose of
      ara-C or adding a third drug.

      Gemtuzumab ozogamicin (Mylotarg ®) is an immunoconjugate between anti-CD33 antibody and a
      cytotoxic antitumor antibiotic, calicheamicin. Mylotarg ® antibody specifically binds to
      CD33, a sialic acid-dependent adhesion protein expressed in over 90% of LMA10. Mylotarg ®
      selectively transports the cytotoxic agent calicheamicin into leukemic cells and
      hematopoietic progenitors differentiated from the myelomonocytic line, while respecting the
      pluripotent hematopoietic stem cells. Calicheamicin is released only after the fixation of
      the antibody anti-CD33 and its internalization by the cell, after which binds to and damages
      the DNA.

      Mylotarg ® is approved in the U.S. for the treatment of CD33 positive AML in first relapse,
      for patients older than 60 years non-candidates for other intensive treatment modalities.

      Since the efficacy of Mylotarg ® is equivalent and its toxicity profile less than the
      conventional therapy, it is logical to conduct a phase II trial exploring the role of
      Mylotarg ® in the early stages of treatment of AML.

      Previous experience with gemtuzumab ozogamicin in relapsed patients led to its use combined
      with induction chemotherapy. The aim was to improve the CR rate reached with the latter and
      reduce relapse after achieving greater leukemic cytoreduction.

      Recent data from the HOVON group support that the administration of G-CSF before and during
      induction chemotherapy decreases the incidence of relapse in patients with AML, particularly
      those considered to have intermediate risk.

      Everything mentioned above justifies to investigate the combination of GO combined with
      chemotherapy with IDR and ara-C in standard 3x7 scheme and analyze the effect of
      sensitization with G-CSF in patients with AML de novo. If the treatment proposed here is
      effective and presents an acceptable toxicity it should be investigated.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Complete Remission of the Disease
time frame: 28 days after chemotherapy
description: Rate of patients that have obtained complete remission. Complete remission is defined as, bone marrow normocellular or slightly hypocellular with proportion of blasts <5%, including the erythroid cell count (and including promonocytes in case of M5), no Auer rods, no extramedullary leukemia, neutrophils and platelets rising. The persistence of minimal residual disease in immunophenotypic study will not invalidate the standard cytogenetic complete remission.
measure: Secondary Toxicity to Mylotarg(R)
time frame: Baseline, weekly during treatment and at month 3 and month 6 after first induction.
description: Hematological toxicity, hepatic and gastrointestinal toxicity, fever and infections, pulmonary complications, duration of hospitalization
measure: Mortality at Induction
time frame: Weekly during treatment, at third month and at 6 months after last administration of Mylotarg
description: all deaths occurring after the first administration of MylotargTM until the time of transplantation with no leukemic relapse has occurred, and all deaths in the 6 first months after administration of the second dose of MylotargTM with no leukemic relapse occurred.
measure: Capacity to Obtain Hematopoietic Progenitor Cells (HPC) for Autotransplantation - DATA NOT COLLECTED
time frame: One month before transplant, expected at 9 months after end of treatment.
description: Rate of patients with capacity to obtain hematopoietic progenitor cells (HPC) for autotransplantation. This analysis has not been performed, because data were not available in sites.
measure: Relapse After 6 Months
time frame: 6 months from complete remission
description: Rate of patients that have relapse after 6 months of obtained complete remission.
measure: Survival After 6 Months
time frame: 6 months after complete remission
description: rate of patients alive within 6 months of obtained complete remission
arm group label: Single arm, three cohorts
arm group type: Experimental
description: Idarubicin, cytarabine, Mylotarg.
intervention type: Drug
intervention name: Mylotarg
description: Cohort 1 version 1.0. GO: 6mg/m^2 (maximum 10 mg), IV infusion, 2 hours, day 1. Idarubicin: 12 mg/m^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine: 100 mg/m^2 IV days 1 to 7, to begin 4 hours after the administration of GO.
Cohort 1.0 version 2.0: GO: 3 mg/m^2 (maximum 5 mg), IV infusion, 2 hours, day 1. Idarubicin: 12 mg/m^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine: 100 mg/m^2 IV days 1 to 7, to begin 4 hours after the administration of GO.
Cohort 2: G-CSF: 150 mcg/m^2, SC, days 0 to 7. GO: 3 mg/m^2 (maximum 5 mg), IV infusion, 2 hours, day 1. Idarubicin: 12 mg/m^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine: 100 mg/m^2 IV continuous infusion on days 1 to 7, to begin 4 hours later after the administration of GO.
arm group label: Single arm, three cohorts
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Jordi Sierra, MD
role: Study Chair
affiliation: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Spain
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute
mesh term: Gemtuzumab
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 