<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/NCT01700413</url>
  </required_header>
  <id_info>
    <org_study_id>IIBSP-CSF-2011-141</org_study_id>
    <nct_id>NCT01700413</nct_id>
  </id_info>
  <brief_title>Efficacy and Toxicity of Increasing Doses of Idarubicin, Cytarabine and G-CSF in Acute Myeloid Leukemia</brief_title>
  <official_title>Treatment of di Novo Acute Myeloid Leukemia With the Combination of Increasing Doses of Idarubicin, Cytarabine and Sensitization (Priming) With G-CSF. A Phase II Prospective Study of Toxicity and Efficacy.</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>
    <collaborator>
      <agency>Ministry of Health, Spain</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </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>
      While several studies have been reported with increasing doses of daunorubicin in the first&#xD;
      line treatment of Acute Myeloid Leukemia (AML), there is no similar experience with&#xD;
      idarubicin as initial treatment of AML.&#xD;
&#xD;
      As idarubicin is the most common treatment used for AML, it is needed to find the optimal&#xD;
      dose for the combination of idarubicin, cytarabine and G_CSF, to explore if this combination&#xD;
      improves the outcomes of current treatments for AML.&#xD;
&#xD;
      The aim of this dose-finding study is to find the optimal dose for the combination of&#xD;
      idarubicin, cytarabine and G-CSF that could improve the response rate, reduce relapse and&#xD;
      improve survival of patients with primary acute myeloid leukemia. This could be a significant&#xD;
      advance in a field where treatment outcomes have stabilized in the last 15 years. This study&#xD;
      will be the basis for further prospective, randomized, multicenter trial comparing idarubicin&#xD;
      maximum tolerated dose, compared to standard treatment with idarubicin and cytarabine,&#xD;
      including raising both arms in G-CSF. The dose of 12 mg/m2 will be administered as control&#xD;
      arm in this future randomized study, which will investigate the benefit of enhanced dose&#xD;
      identified as optimal in this phase II pilot study.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">April 2015</completion_date>
  <primary_completion_date type="Actual">October 2013</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>Rate of complete remissions (CR)</measure>
    <time_frame>From 28 up to 56 days after first induction</time_frame>
    <description>Identify the highest dose of idarubicin in combination with cytarabine and G-CSF that produces a CR rate equal to or greater than 65% with tolerable toxicity.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Rate of patients with adverse events as a measure of safety and tolerability</measure>
    <time_frame>Weekly during treatment, and on months 3 and 6 after complete response</time_frame>
    <description>Hematologic toxicity Gastrointestinal and liver toxicity Cardiac Toxicity Fever and infection Pulmonary complications Duration of hospitalization Mortality and causes of death induction.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of hospitalization</measure>
    <time_frame>From the inclusion until 9 months after inclusion.</time_frame>
    <description>Number of days in which the patient is hospitalized.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality (as rate) related to study treatment</measure>
    <time_frame>Weekly during treatment, 3 months after complete remission, 6 months after complete remission and 9 months after complete remission</time_frame>
    <description>Causes of death, mortality related treatment, mortality in induction.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relapse at 6 months</measure>
    <time_frame>6 months from complete remission, expected to be within 9 months from inclusion.</time_frame>
    <description>Rate of patients that have relapsed within 6 months after complete remission.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Survival at 9 months from diagnosis</measure>
    <time_frame>9 months after diagnoses</time_frame>
    <description>Rate of patients alive at 9 months after diagnosis.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">48</enrollment>
  <condition>Di Novo Acute Myeloid Leukemia</condition>
  <arm_group>
    <arm_group_label>Idarubicin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cohort 1: Idarubicin 14 mg/m2 (day 1-3), Cytarabine 200 mg/m2 (Days 1-7), G-CSF 150 mcg/m2/day Cohort 2: Idarubicin 16 mg/m2 (day 1-3), Cytarabine 200 mg/m2 (Days 1-7), G-CSF 150 mcg/m2/day Cohort 3: Idarubicin 18 mg/m2 (day 1-3), Cytarabine 200 mg/m2 (Days 1-7), G-CSF 150 mcg/m2/day</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Idarubicin</intervention_name>
    <arm_group_label>Idarubicin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Informed consent signature Patients with newly diagnosed AML, classified according to WHO&#xD;
        criteria. Age more than or equal to 18 and less than or equal to 70 years.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Patients previously treated with chemotherapy for their AML other than hydroxyurea.&#xD;
&#xD;
        Acute promyelocytic leukemia with t (15; 17). Blast crisis of chronic myeloid leukemia.&#xD;
        Leukemias that appear after other myeloproliferative neoplasms. Leukemias ensuing&#xD;
        myelodysplastic syndromes after more than 6 months. Presence of other malignancies in&#xD;
        activity. AML secondary to chemo-radiotherapy treatment for other malignancies. Abnormal&#xD;
        renal and hepatic function, with creatinine value and / or bilirubin 2 times the normal&#xD;
        limit value, except where the alterations are attributable to leukemia.&#xD;
&#xD;
        Patients with markedly reduced ejection fraction (less than 45%), symptomatic heart&#xD;
        failure, or both of the normal value of the center.&#xD;
&#xD;
        Patients with serious concomitant psychiatric or neurological disease. HIV-positive.&#xD;
        Pregnancy or breastfeeding&#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>Salut Brunet, 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 Universitari Germans Trias I Pujol de Badalona</name>
      <address>
        <city>Badalona</city>
        <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>Hospitals Vall D'Hebron</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinic I Provincial de Barcelona</name>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clínico Universitario de Valencia</name>
      <address>
        <city>Valencia</city>
        <zip>46010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>January 2016</verification_date>
  <study_first_submitted>October 1, 2012</study_first_submitted>
  <study_first_submitted_qc>October 2, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 4, 2012</study_first_posted>
  <last_update_submitted>January 27, 2016</last_update_submitted>
  <last_update_submitted_qc>January 27, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 28, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>acute</keyword>
  <keyword>myeloid</keyword>
  <keyword>leukemia</keyword>
  <keyword>CETLAM</keyword>
  <keyword>Idarubicin</keyword>
  <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>Idarubicin</mesh_term>
  </intervention_browse>
  <!-- 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/NCT01700413
org study id: IIBSP-CSF-2011-141
nct id: NCT01700413
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
While several studies have been reported with increasing doses of daunorubicin in the first
      line treatment of Acute Myeloid Leukemia (AML), there is no similar experience with
      idarubicin as initial treatment of AML.

      As idarubicin is the most common treatment used for AML, it is needed to find the optimal
      dose for the combination of idarubicin, cytarabine and G_CSF, to explore if this combination
      improves the outcomes of current treatments for AML.

      The aim of this dose-finding study is to find the optimal dose for the combination of
      idarubicin, cytarabine and G-CSF that could improve the response rate, reduce relapse and
      improve survival of patients with primary acute myeloid leukemia. This could be a significant
      advance in a field where treatment outcomes have stabilized in the last 15 years. This study
      will be the basis for further prospective, randomized, multicenter trial comparing idarubicin
      maximum tolerated dose, compared to standard treatment with idarubicin and cytarabine,
      including raising both arms in G-CSF. The dose of 12 mg/m2 will be administered as control
      arm in this future randomized study, which will investigate the benefit of enhanced dose
      identified as optimal in this phase II pilot study.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Rate of complete remissions (CR)
time frame: From 28 up to 56 days after first induction
description: Identify the highest dose of idarubicin in combination with cytarabine and G-CSF that produces a CR rate equal to or greater than 65% with tolerable toxicity.
measure: Rate of patients with adverse events as a measure of safety and tolerability
time frame: Weekly during treatment, and on months 3 and 6 after complete response
description: Hematologic toxicity Gastrointestinal and liver toxicity Cardiac Toxicity Fever and infection Pulmonary complications Duration of hospitalization Mortality and causes of death induction.
measure: Duration of hospitalization
time frame: From the inclusion until 9 months after inclusion.
description: Number of days in which the patient is hospitalized.
measure: Mortality (as rate) related to study treatment
time frame: Weekly during treatment, 3 months after complete remission, 6 months after complete remission and 9 months after complete remission
description: Causes of death, mortality related treatment, mortality in induction.
measure: Relapse at 6 months
time frame: 6 months from complete remission, expected to be within 9 months from inclusion.
description: Rate of patients that have relapsed within 6 months after complete remission.
measure: Survival at 9 months from diagnosis
time frame: 9 months after diagnoses
description: Rate of patients alive at 9 months after diagnosis.
arm group label: Idarubicin
arm group type: Experimental
description: Cohort 1: Idarubicin 14 mg/m2 (day 1-3), Cytarabine 200 mg/m2 (Days 1-7), G-CSF 150 mcg/m2/day Cohort 2: Idarubicin 16 mg/m2 (day 1-3), Cytarabine 200 mg/m2 (Days 1-7), G-CSF 150 mcg/m2/day Cohort 3: Idarubicin 18 mg/m2 (day 1-3), Cytarabine 200 mg/m2 (Days 1-7), G-CSF 150 mcg/m2/day
intervention type: Drug
intervention name: Idarubicin
arm group label: Idarubicin
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Salut Brunet, MD
role: Study Chair
affiliation: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
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: Idarubicin