<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/NCT01716793</url>
  </required_header>
  <id_info>
    <org_study_id>AML-99</org_study_id>
    <nct_id>NCT01716793</nct_id>
  </id_info>
  <brief_title>Risk-adapted Therapy for Adult Acute Myeloid Leukemia.</brief_title>
  <official_title>Risk Adapted Treatment for Primary AML in Adults up to the Age of 60 Years.</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>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      In a protocol of treatment of AML used in 1994 for adults with AML up to the age of 50 years,&#xD;
      the Spanish CETLAM group showed a complete remission rate 75 % using the combination of&#xD;
      daunorubicin (60 mg/m2, 3 days) plus conventional dose cytarabine (100mg/m2/day in continuous&#xD;
      infusion during 7 days) and etoposide (100mg/m2 IV/day 3 days). If idarubicin (10 mg/m2, 3&#xD;
      days) was administered instead of daunorubicin, the complete remission (CR) rate in adults up&#xD;
      to 60 years was 75%. To improve the proportion of CRs and to decrease relapse rate appearing&#xD;
      in 50% of patients, the phase II AML-99 trial includes intermediate dose-cytarabine during&#xD;
      induction and risk-adapted post remission treatment based on the improvement in prognostic&#xD;
      characterization of AML and the implementation of novel transplantation techniques.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Induction chemotherapy: idarubicin (12mg/m2/day intravenous), intermediate-dose cytarabine&#xD;
      (500mg/m2/12h, intravenous) and etoposide (100mg/m2/day, intravenous) in 3+7+3 schedule. This&#xD;
      induction therapy is repeated if complete remission (CR) is not achieved after the first&#xD;
      course of treatment.&#xD;
&#xD;
      Consolidation therapy: mitoxantrone (12mg/m2/day, intravenous, days 4, 5 and 6) and&#xD;
      intermediate-dose cytarabine (500mg/m2/12h from day 1 to 6).&#xD;
&#xD;
      Risk-stratification according to cytogenetics, courses to CR and availability of an&#xD;
      HLA-identical sibling:&#xD;
&#xD;
        -  Patients in the favorable cytogenetics group [t(8;21), inv(16) or t(16;16)] are treated&#xD;
           with high-dose cytarabine (3g/m2/12h, intravenous, days 1, 3 and 5).&#xD;
&#xD;
        -  Patients in intermediate cytogenetics group (normal karyotype and a single course to&#xD;
           achieve the CR) receive an autologous peripheral blood stem cell (PBSC) transplant,&#xD;
           regardless of having an HLA-identical sibling.&#xD;
&#xD;
        -  The remaining patients are considered in the high-risk group and are treated with&#xD;
           autologous or allogeneic PBSC transplantation depending on the availability of a sibling&#xD;
           donor. In allotransplants, CD34+ cell selection of hematopoietic cells is performed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 1998</start_date>
  <completion_date type="Actual">November 2003</completion_date>
  <primary_completion_date type="Actual">September 1998</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 rate.</measure>
    <time_frame>2 months.</time_frame>
    <description>Analyze the efficacy and toxicity of IDICE (idarubicin, intermediate doses of ara-C and etoposide) to achieve complete remission.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Disease free survival.</measure>
    <time_frame>4 years.</time_frame>
    <description>Analyze the disease free survival (DFS)of patients in remission, with a therapeutic strategy adjusted to the prognostic factors.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Evaluations of minimal residual disease (MRD) by flow cytometry during and after treatment.</measure>
    <time_frame>4 years.</time_frame>
    <description>Study of the immunophenotypic characteristics of the leukemic population at diagnosis and evaluation of MRD during different treatment phases and follow-up.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Feasibility to mobilize and collect autologous PBSC after consolidation phase.</measure>
    <time_frame>6 months.</time_frame>
    <description>Evaluation of mobilization failures.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluations of the CD34+ cell selection procedure and allogeneic peripheral blood stem cell (PBSC)transplantation outcome.</measure>
    <time_frame>4 years.</time_frame>
    <description>CD34+ cell selection from PBSC of HLA-identical siblings. Conditioning regimen. Infusion and post-transplant follow-up.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">354</enrollment>
  <condition>Leukemia, Myelocytic, Acute</condition>
  <arm_group>
    <arm_group_label>Risk-adapted postremission treatment</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Ara-C, autologous transplantation, Allogeneic HLA-identical sibling transplantation depending on risk factors (cytogenetics, courses to CR)and availability of an HLA-identical sibling, CD34+ selection.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ara-C</intervention_name>
    <description>Intermediate dose during induction phase to remission.&#xD;
High-dose during consolidation phase in patients with favorable cytogenetics.</description>
    <arm_group_label>Risk-adapted postremission treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Autologous transplantation</intervention_name>
    <description>In patients with normal karyotype and one cycle of chemotherapy to achieve complete remission.&#xD;
In patients with other cytogenetics without HLA-Identical sibling.</description>
    <arm_group_label>Risk-adapted postremission treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Allogeneic HLA-identical sibling transplantation</intervention_name>
    <description>Patients without favorable or normal karyotype(and one course to CR).&#xD;
Patients with normal karyotype who need two cycles of chemotherapy to achieve CR, and other cytogenetics.</description>
    <arm_group_label>Risk-adapted postremission treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>CD34+ selection</intervention_name>
    <description>In allotransplants, it is performed a CD34+ cell selection of peripheral blood stem cell transplantation.</description>
    <arm_group_label>Risk-adapted postremission treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with newly diagnosed AML, classified by FAB criteria&#xD;
&#xD;
          -  Age not superior to 60 years&#xD;
&#xD;
          -  Verbal informed consent for the chemotherapy and written for the mobilization and stem&#xD;
             cell transplantation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients treated previously for its AML with other chemotherapy different from&#xD;
             hydroxyurea&#xD;
&#xD;
          -  Acute promyelocytic leukemia (M3)&#xD;
&#xD;
          -  Chronic myeloid leukemia in blastic crisis&#xD;
&#xD;
          -  Leukemias appearing after other myeloproliferative processes&#xD;
&#xD;
          -  Leukemias surviving after myelodysplastic syndromes with more than 6 months of&#xD;
             evolution&#xD;
&#xD;
          -  Presence of other neoplastic disease in activity&#xD;
&#xD;
          -  Secondary AML which had appeared after cured malignancies (for instance Hodgkin&#xD;
             disease) and those who are still exposed to alkylant agents or radiation&#xD;
&#xD;
          -  Renal and hepatic abnormal function with creatinine values and/or bilirubin two times&#xD;
             higher than the normal threshold, except when this alteration could be attributed to&#xD;
             the leukemia&#xD;
&#xD;
          -  Patients with a fraction of ejection very low (inferior to 40%), symptomatic cardiac&#xD;
             insufficiency or both&#xD;
&#xD;
          -  Patients with a grave concomitant neurological or psychiatric disease&#xD;
&#xD;
          -  Positivity of HIV (donor and/or receptor)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jorge Sierra, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau</affiliation>
  </overall_official>
  <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 Germans Trias i Pujol</name>
      <address>
        <city>Badalona</city>
        <state>Barcelona</state>
        <zip>08916</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ICO Hospital Universitari de Bellvitge</name>
      <address>
        <city>L'Hospitalet del Llobregat</city>
        <state>Barcelona</state>
        <zip>08907</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital A Coruña</name>
      <address>
        <city>A Coruña</city>
        <state>Coruña</state>
        <zip>15006</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Son Espases</name>
      <address>
        <city>Palma de Mallorca</city>
        <state>Mallorca</state>
        <zip>07198</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Joan Bargay</name>
      <address>
        <city>Palma de Mallorca</city>
        <state>Mallorca</state>
        <zip>07198</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Verge de la Cinta</name>
      <address>
        <city>Tortosa</city>
        <state>Tarragona</state>
        <zip>43517</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital del Mar</name>
      <address>
        <city>Barcelona</city>
        <zip>08003</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Medico Teknon</name>
      <address>
        <city>Barcelona</city>
        <zip>08022</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 Vall d'Hebron</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jordi Esteve</name>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Universitari de Girona Dr. Josep Trueta</name>
      <address>
        <city>Girona</city>
        <zip>17007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Arnau de Vilanova</name>
      <address>
        <city>Lleida</city>
        <zip>25006</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen de la Victoria</name>
      <address>
        <city>Malaga</city>
        <zip>29010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitario de Murcia</name>
      <address>
        <city>Murcia</city>
        <zip>30008</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Joan XXIII</name>
      <address>
        <city>Tarragona</city>
        <zip>43007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mutua de Terrassa</name>
      <address>
        <city>Terrassa</city>
        <zip>08225</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>
    <facility>
      <name>Hospital Universitario Rio Hortega</name>
      <address>
        <city>Valladolid</city>
        <zip>41010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>October 2012</verification_date>
  <study_first_submitted>October 22, 2012</study_first_submitted>
  <study_first_submitted_qc>October 29, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 30, 2012</study_first_posted>
  <last_update_submitted>October 31, 2012</last_update_submitted>
  <last_update_submitted_qc>October 31, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 1, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Primary AML</keyword>
  <keyword>Risk-adapted treatment</keyword>
  <keyword>Hematopoietic transplantation</keyword>
  <keyword>CD34+ cell selection</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>
  <!-- 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/NCT01716793
org study id: AML-99
nct id: NCT01716793
lead sponsor: 
has dmc: Yes
In a protocol of treatment of AML used in 1994 for adults with AML up to the age of 50 years,
      the Spanish CETLAM group showed a complete remission rate 75 % using the combination of
      daunorubicin (60 mg/m2, 3 days) plus conventional dose cytarabine (100mg/m2/day in continuous
      infusion during 7 days) and etoposide (100mg/m2 IV/day 3 days). If idarubicin (10 mg/m2, 3
      days) was administered instead of daunorubicin, the complete remission (CR) rate in adults up
      to 60 years was 75%. To improve the proportion of CRs and to decrease relapse rate appearing
      in 50% of patients, the phase II AML-99 trial includes intermediate dose-cytarabine during
      induction and risk-adapted post remission treatment based on the improvement in prognostic
      characterization of AML and the implementation of novel transplantation techniques.
Induction chemotherapy: idarubicin (12mg/m2/day intravenous), intermediate-dose cytarabine
      (500mg/m2/12h, intravenous) and etoposide (100mg/m2/day, intravenous) in 3+7+3 schedule. This
      induction therapy is repeated if complete remission (CR) is not achieved after the first
      course of treatment.

      Consolidation therapy: mitoxantrone (12mg/m2/day, intravenous, days 4, 5 and 6) and
      intermediate-dose cytarabine (500mg/m2/12h from day 1 to 6).

      Risk-stratification according to cytogenetics, courses to CR and availability of an
      HLA-identical sibling:

        -  Patients in the favorable cytogenetics group [t(8;21), inv(16) or t(16;16)] are treated
           with high-dose cytarabine (3g/m2/12h, intravenous, days 1, 3 and 5).

        -  Patients in intermediate cytogenetics group (normal karyotype and a single course to
           achieve the CR) receive an autologous peripheral blood stem cell (PBSC) transplant,
           regardless of having an HLA-identical sibling.

        -  The remaining patients are considered in the high-risk group and are treated with
           autologous or allogeneic PBSC transplantation depending on the availability of a sibling
           donor. In allotransplants, CD34+ cell selection of hematopoietic cells is performed.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Complete remission rate.
time frame: 2 months.
description: Analyze the efficacy and toxicity of IDICE (idarubicin, intermediate doses of ara-C and etoposide) to achieve complete remission.
measure: Disease free survival.
time frame: 4 years.
description: Analyze the disease free survival (DFS)of patients in remission, with a therapeutic strategy adjusted to the prognostic factors.
measure: Evaluations of minimal residual disease (MRD) by flow cytometry during and after treatment.
time frame: 4 years.
description: Study of the immunophenotypic characteristics of the leukemic population at diagnosis and evaluation of MRD during different treatment phases and follow-up.
measure: Feasibility to mobilize and collect autologous PBSC after consolidation phase.
time frame: 6 months.
description: Evaluation of mobilization failures.
measure: Evaluations of the CD34+ cell selection procedure and allogeneic peripheral blood stem cell (PBSC)transplantation outcome.
time frame: 4 years.
description: CD34+ cell selection from PBSC of HLA-identical siblings. Conditioning regimen. Infusion and post-transplant follow-up.
arm group label: Risk-adapted postremission treatment
arm group type: Other
description: Ara-C, autologous transplantation, Allogeneic HLA-identical sibling transplantation depending on risk factors (cytogenetics, courses to CR)and availability of an HLA-identical sibling, CD34+ selection.
intervention type: Drug
intervention name: Ara-C
description: Intermediate dose during induction phase to remission.
High-dose during consolidation phase in patients with favorable cytogenetics.
arm group label: Risk-adapted postremission treatment
intervention type: Other
intervention name: Autologous transplantation
description: In patients with normal karyotype and one cycle of chemotherapy to achieve complete remission.
In patients with other cytogenetics without HLA-Identical sibling.
arm group label: Risk-adapted postremission treatment
intervention type: Other
intervention name: Allogeneic HLA-identical sibling transplantation
description: Patients without favorable or normal karyotype(and one course to CR).
Patients with normal karyotype who need two cycles of chemotherapy to achieve CR, and other cytogenetics.
arm group label: Risk-adapted postremission treatment
intervention type: Other
intervention name: CD34+ selection
description: In allotransplants, it is performed a CD34+ cell selection of peripheral blood stem cell transplantation.
arm group label: Risk-adapted postremission treatment
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Jorge Sierra, MD
role: Principal Investigator
affiliation: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
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: 
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country: Spain
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute