<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/NCT02198482</url>
  </required_header>
  <id_info>
    <org_study_id>AMLSG 20-13</org_study_id>
    <secondary_id>2014-000477-39</secondary_id>
    <nct_id>NCT02198482</nct_id>
  </id_info>
  <brief_title>Trial of Intensive Chemotherapy With or Without Volasertib in Patients With Newly Diagnosed High-Risk Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML)</brief_title>
  <official_title>Dose Finding Safety Run-in Phase Followed by a Randomized Phase II Trial of Intensive Chemotherapy With or Without Volasertib (BI 6727) Administered Prior or After Chemotherapy in Patients With Newly Diagnosed High-Risk Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Ulm</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Ulm</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Randomized Phase II Trial of Intensive Chemotherapy With or Without Volasertib (BI 6727) in&#xD;
      Patients With Newly Diagnosed High-Risk Myelodysplastic Syndrome (MDS) and Acute Myeloid&#xD;
      Leukemia (AML)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The trial is a randomized, Phase II, open label multi-center trial in adult patients with&#xD;
      newly diagnosed AML or high-risk MDS as defined in the inclusion/exclusion criteria.&#xD;
&#xD;
      An initial safety run-in study will be performed administering intensive induction therapy&#xD;
      consisting of daunorubicin and cytarabine with the study drug volasertib administered prior&#xD;
      or after chemotherapy, as well as consolidation therapy consisting of intermediate-dose&#xD;
      cytarabine with the study drug volasertib administered prior or after chemotherapy. After&#xD;
      establishing the volasertib dose, the randomized Phase II portion of the trial will begin:&#xD;
&#xD;
      Patients will be equally randomized to DA (daunorubicin, cytarabine), V-DA (volasertib&#xD;
      administered prior to daunorubicin, cytarabine), and DA-V (volasertib administered after&#xD;
      daunorubicin, cytarabine). All patients will receive a second induction cycle with reduced&#xD;
      daunorubicin and cytarabine doses. Patients refractory to the first induction cycle and&#xD;
      patients not achieving a CR/CRi after two induction cycles will be off-study and followed up.&#xD;
&#xD;
      Patients in CR/CRi after induction therapy will proceed to consolidation therapy.&#xD;
      Consolidation will be stratified based on the genetic risk profile (according to ELN&#xD;
      criteria) and patient-related factors (e.g., age, HCT-CI, comorbidities, patient wish).&#xD;
      Patients with a favorable genetic risk profile and those patients considered ineligible for&#xD;
      allogeneic HCT will receive repetitive cycles of consolidation according to initial&#xD;
      randomization, either MiDAC, V-MiDAC (volasertib administered prior to cytarabine), or&#xD;
      MiDAC-V (volasertib administered after cytarabine). All other patients are assigned to&#xD;
      allogeneic HCT.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    development program of study drug volasertib was stopped by Boehringer Ingelheim due to&#xD;
    manufacturing problems&#xD;
  </why_stopped>
  <start_date>February 2016</start_date>
  <completion_date type="Actual">November 2016</completion_date>
  <primary_completion_date type="Actual">November 2016</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Rate of complete remission (CR) and CR with incomplete blood count recovery (CRi)</measure>
    <time_frame>2 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cumulative incidence of relapse</measure>
    <time_frame>4 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative incidence of death</measure>
    <time_frame>4 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relapse-free survival</measure>
    <time_frame>4 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Event-free survival</measure>
    <time_frame>4 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>4 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence and intensity of adverse events</measure>
    <time_frame>8 months</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Acute Myeloid Leukemia (AML)</condition>
  <condition>High-risk Myelodysplastic Syndrome (MDS)</condition>
  <arm_group>
    <arm_group_label>Daunorubicin, Cytarabine (DA)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>DA&#xD;
Induction I:&#xD;
Daunorubicin 60 mg/m² i.v., d 1-3&#xD;
Cytarabine 100 mg/m² cont. i.v., d 1-7&#xD;
Induction II:&#xD;
Daunorubicin 50 mg/m² i.v. d 1-3&#xD;
Cytarabine 100 mg/m² cont. i.v., d 1-5&#xD;
Consolidation therapy:&#xD;
Patients with genetic favourable risk and those patients not eligible for allogeneic HSCT due to comorbidities, high HCT-CI or patient wish will proceed to 3 cycles of age-adapted consolidation therapy with mitoxantrone and intermediate-dose cytarabine (MiDAC).&#xD;
Mitoxantrone Younger adults (18 to 60 yrs): 10 mg/m2 by i.v. on day 1. Elderly patients (&gt;60 yrs): 8 mg/m2 by i.v. infusion on day 1.&#xD;
Intermediate-dose cytarabine:&#xD;
Younger adults (18 to 60 yrs): 1500 mg/m2 q12h on days 1-3 Elderly patients (&gt;60 yrs): 1000 mg/m2 q12h on days 1-3 An allogeneic HSCT is intended for patients with intermediate I/II and adverse-risk genetics. Optionally, one cycle of consolidation with MiDAC may be given prior to alloHSCT.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Volasertib, Daunorubicin, Cytarabine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>VDA&#xD;
Induction I&#xD;
Volasertib i.v., d1&#xD;
Daunorubicin 60 mg/m² i.v., d 2-4&#xD;
Cytarabine 100 mg/m² cont. i.v., d 2-8 Induction II&#xD;
Volasertib i.v., d1&#xD;
Daunorubicin 50 mg/m² i.v. d 2-4&#xD;
Cytarabine 100 mg/m² cont. i.v., d 2-6&#xD;
Consolidation therapy:&#xD;
Patients with genetic favourable risk and those patients not eligible for allogeneic HSCT will proceed to 3 cycles of age-adapted consolidation therapy with mitoxantrone and intermediate-dose cytarabine in combination with Volasertib (V-MiDAC).&#xD;
Volasertib i.v., d1&#xD;
Mitoxantrone Younger adults (18 to 60 yrs): 10 mg/m2 by i.v. on day 2. Elderly patients (&gt;60 yrs): 8 mg/m2 by i.v. on day 2.&#xD;
Intermediate-dose cytarabine:&#xD;
Younger adults (18 to 60 yrs): 1500 mg/m2 q12h on days 2-4 Elderly patients (&gt;60 yrs): 1000 mg/m2 q12h on days 2-4 An allogeneic HSCT is intended for patients with intermediate I/II and adverse-risk genetics. Optionally, one cycle of consolidation with V-MiDAC may be given prior to alloHSCT.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Daunorubicin, Cytarabine, Volasertib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>DAV&#xD;
Induction I&#xD;
Volasertib i.v., d7&#xD;
Daunorubicin 60 mg/m² i.v., d 1-3&#xD;
Cytarabine 100 mg/m² i.v., d 1-7 Induction II&#xD;
Volasertib i.v., d5&#xD;
Daunorubicin 50 mg/m² i.v. d 1-3&#xD;
Cytarabine 100 mg/m² cont. i.v., d 1-5&#xD;
Consolidation therapy:&#xD;
Patients with genetic fav. risk and those patients not eligible for alloHSCT will proceed to 3 cycles of age-adapted consolidation therapy with mitoxantrone and intermediate-dose cytarabine in combination with Volasertib (MiDAC-V).&#xD;
Volasertib i.v., d4&#xD;
Mitoxantrone Younger adults (18 to 60 yrs): 10 mg/m2 by i.v. on day 1. Elderly patients (&gt;60 yrs): 8 mg/m2 by i.v. on day 1.&#xD;
Intermediate-dose cytarabine:&#xD;
Younger adults (18 to 60 yrs): 1500 mg/m2 q12h on days 1-3 Elderly patients (&gt;60 yrs): 1000 mg/m2 q12h on days 1-3 An allogeneic HSCT is intended for patients with intermediate I/II and adverse-risk genetics. Optionally, one cycle of consolidation with MiDAC-V may be given prior to alloHSCT.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Volasertib</intervention_name>
    <arm_group_label>Daunorubicin, Cytarabine, Volasertib</arm_group_label>
    <arm_group_label>Volasertib, Daunorubicin, Cytarabine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cytarabine</intervention_name>
    <arm_group_label>Daunorubicin, Cytarabine (DA)</arm_group_label>
    <arm_group_label>Daunorubicin, Cytarabine, Volasertib</arm_group_label>
    <arm_group_label>Volasertib, Daunorubicin, Cytarabine</arm_group_label>
    <other_name>ARA-cell</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Daunorubicin</intervention_name>
    <arm_group_label>Daunorubicin, Cytarabine (DA)</arm_group_label>
    <arm_group_label>Daunorubicin, Cytarabine, Volasertib</arm_group_label>
    <arm_group_label>Volasertib, Daunorubicin, Cytarabine</arm_group_label>
    <other_name>Daunoplastin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mitoxantrone</intervention_name>
    <arm_group_label>Daunorubicin, Cytarabine (DA)</arm_group_label>
    <arm_group_label>Daunorubicin, Cytarabine, Volasertib</arm_group_label>
    <arm_group_label>Volasertib, Daunorubicin, Cytarabine</arm_group_label>
    <other_name>Novantron</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with confirmed diagnosis of acute myeloid leukemia (AML) or related precursor&#xD;
             neoplasm, or acute leukemia of ambiguous lineage according to the current World Health&#xD;
             Organization (WHO) classification, or patients with myelodysplastic syndrome (MDS)&#xD;
             classified as refractory anemia with excess blasts-2 (RAEB-2)&#xD;
&#xD;
          -  Consent for a genetic assessment in AMLSG central laboratory&#xD;
&#xD;
          -  Patients considered eligible for intensive chemotherapy&#xD;
&#xD;
          -  ECOG performance status of ≤ 2&#xD;
&#xD;
          -  Age &gt;= 18; there is no upper age limit&#xD;
&#xD;
          -  No prior chemotherapy for acute leukemia except hydroxyurea for up to 5 days during&#xD;
             the diagnostic screening phase; patients may have received prior therapy for&#xD;
             myelodysplastic syndrome.&#xD;
&#xD;
          -  Non-pregnant and non-nursing. Due to the teratogenic potential of volasertib in&#xD;
             humans, pregnant or nursing patients may not be enrolled. Women of childbearing&#xD;
             potential (WOCBP) must have a negative serum or urine pregnancy test within a&#xD;
             sensitivity of at least 25 mIU/mL within 72 hours prior to registration. Women of&#xD;
             child-bearing potential must either commit to continued abstinence from heterosexual&#xD;
             intercourse or begin TWO acceptable methods of birth control - one highly effective&#xD;
             method (e.g., IUD, hormonal, tubal ligation, or partner's vasectomy), and one&#xD;
             additional effective method (e.g., latex condom, diaphragm, or cervical cap) for 6&#xD;
             months after therapy is stopped. &quot;Women of childbearing potential&quot; is defined as a&#xD;
             sexually active mature woman who has not undergone a hysterectomy or who has had&#xD;
             menses at any time in the preceding 24 consecutive months.&#xD;
&#xD;
          -  Men must agree not to father a child and must use a latex condom during any sexual&#xD;
             contact with women of childbearing potential while receiving therapy and for 6 months&#xD;
             after therapy is stopped, even if they have undergone a successful vasectomy&#xD;
&#xD;
          -  Signed written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with acute promyelocytic leukemia exhibiting t(15;17)(q22;q12); PML-RARA, or&#xD;
             with variant translocations&#xD;
&#xD;
          -  Prior treatment with volasertib or any other PLK1 inhibitor&#xD;
&#xD;
          -  Performance status WHO &gt;2 (see Appendix I)&#xD;
&#xD;
          -  Patients with ejection fraction &lt;50% by echocardiography within 14 days of day 1&#xD;
&#xD;
          -  QTcF prolongation &gt;470 ms or QT prolongation deemed clinically relevant by the&#xD;
             investigator (e.g., congenital long QT syndrome). The QTcF will be calculated as the&#xD;
             mean of 3 ECGs taken at screening.&#xD;
&#xD;
          -  Any clinically significant, advanced or unstable disease or history of that may&#xD;
             interfere with primary or secondary variable evaluations or put the patient at special&#xD;
             risk, such as:&#xD;
&#xD;
               -  creatinine &gt;1.5x upper normal serum level;&#xD;
&#xD;
               -  total bilirubin, AST or AP &gt;2.5x upper normal serum level;&#xD;
&#xD;
               -  heart failure NYHA III/IV,&#xD;
&#xD;
               -  uncontrolled hypertension,&#xD;
&#xD;
               -  unstable angina,&#xD;
&#xD;
               -  serious cardiac arrhythmia;&#xD;
&#xD;
               -  severe obstructive or restrictive ventilation disorder&#xD;
&#xD;
               -  uncontrolled infection&#xD;
&#xD;
          -  Patients with a &quot;currently active&quot; second malignancy other than non-melanoma skin&#xD;
             cancers. Patients are not considered to have a &quot;currently active&quot; malignancy, if they&#xD;
             have completed therapy and are considered by their physician to be at less than 30%&#xD;
             risk of relapse within one year.&#xD;
&#xD;
          -  Severe neurological or psychiatric disorder interfering with ability of giving an&#xD;
             informed consent&#xD;
&#xD;
          -  Known or suspected active alcohol or drug abuse&#xD;
&#xD;
          -  Known positive for HIV, active HBV, HCV, or hepatitis A infection&#xD;
&#xD;
          -  Hematologic disorder independent of leukemia&#xD;
&#xD;
          -  No consent for registration, storage and processing of the individual disease&#xD;
             characteristics and course as well as information of the family physician and/or other&#xD;
             physicians involved in the treatment of the patient about study participation.&#xD;
&#xD;
          -  No consent for biobanking.&#xD;
&#xD;
          -  Current participation in any other interventional clinical study within 30 days before&#xD;
             the first administration of the investigational product or at any time during the&#xD;
             study&#xD;
&#xD;
          -  Breast feeding women or women with a positive pregnancy test at Screening visit&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hartmut Döhner, Prof. Dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>AMLSG Clinical Trials Office</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Peter Paschka, MD</last_name>
    <role>Study Chair</role>
    <affiliation>University Hospital Ulm</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital Aschaffenburg</name>
      <address>
        <city>Aschaffenburg</city>
        <zip>63739</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Helios Hospital Bad Saarow</name>
      <address>
        <city>Bad Saarow</city>
        <zip>15526</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vivantes Hospital Am Urban</name>
      <address>
        <city>Berlin</city>
        <zip>10967</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vivantes Hospital Neukölln</name>
      <address>
        <city>Berlin</city>
        <zip>12351</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charite Berlin Campus Virchow Hospital</name>
      <address>
        <city>Berlin</city>
        <zip>13353</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Knappschaftskrankenhaus Bochum-Langendeer</name>
      <address>
        <city>Bochum</city>
        <zip>44892</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Bonn</name>
      <address>
        <city>Bonn</city>
        <zip>53105</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Community Hospital Braunschweig</name>
      <address>
        <city>Braunschweig</city>
        <zip>38114</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Darmstadt</name>
      <address>
        <city>Darmstadt</city>
        <zip>64283</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Düsseldorf</name>
      <address>
        <city>Düsseldorf</city>
        <zip>40225</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Essen, Protestant Hospital Essen-Werden</name>
      <address>
        <city>Essen</city>
        <zip>45239</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Esslingen</name>
      <address>
        <city>Esslingen</city>
        <zip>73730</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Malteser Hospital St. Franziskus</name>
      <address>
        <city>Flensburg</city>
        <zip>24939</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Frankfurt-Höchst</name>
      <address>
        <city>Frankfurt</city>
        <zip>65929</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical Care Unit Osthessen</name>
      <address>
        <city>Fulda</city>
        <zip>36043</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Gießen</name>
      <address>
        <city>Gießen</city>
        <zip>35392</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wilhelm-Anton-Hospital Goch</name>
      <address>
        <city>Goch</city>
        <zip>47574</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Göttingen</name>
      <address>
        <city>Göttingen</city>
        <zip>37075</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Hamburg-Eppendorf</name>
      <address>
        <city>Hamburg</city>
        <zip>20246</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Asklepios Hospital Altona</name>
      <address>
        <city>Hamburg</city>
        <zip>22763</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Hanau</name>
      <address>
        <city>Hanau</city>
        <zip>63450</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>KRH Hospital Siloah-Oststadt-Heidehaus</name>
      <address>
        <city>Hannover</city>
        <zip>30459</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hannover Medical School</name>
      <address>
        <city>Hannover</city>
        <zip>30625</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SLK-Hospital Heilbronn</name>
      <address>
        <city>Heilbronn</city>
        <zip>74078</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Marienhospital Herne</name>
      <address>
        <city>Herne</city>
        <zip>44625</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital des Saarlandes</name>
      <address>
        <city>Homburg/Saar</city>
        <zip>66421</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Community Hospital Karlsruhe</name>
      <address>
        <city>Karlsruhe</city>
        <zip>76133</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Schleswig-Holstein</name>
      <address>
        <city>Kiel</city>
        <zip>24105</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Caritas Hospital Lebach</name>
      <address>
        <city>Lebach</city>
        <zip>66822</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Lippe-Lemgo</name>
      <address>
        <city>Lemgo</city>
        <zip>32657</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Magdeburg</name>
      <address>
        <city>Magdeburg</city>
        <zip>39120</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Johannes Gutenberg Mainz</name>
      <address>
        <city>Mainz</city>
        <zip>55131</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johannes Wesling Hospital Minden</name>
      <address>
        <city>Minden</city>
        <zip>32429</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stauferklinikum Schwäbisch-Gmünd</name>
      <address>
        <city>Mutlangen</city>
        <zip>73557</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Schwabing</name>
      <address>
        <city>München</city>
        <zip>80804</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital rechts der Isar München</name>
      <address>
        <city>München</city>
        <zip>81675</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Oldenburg</name>
      <address>
        <city>Oldenburg</city>
        <zip>26133</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Passau</name>
      <address>
        <city>Passau</city>
        <zip>94032</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Stuttgart</name>
      <address>
        <city>Stuttgart</city>
        <zip>70174</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Diakonie Hospital Stuttgart</name>
      <address>
        <city>Stuttgart</city>
        <zip>70176</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Traunstein</name>
      <address>
        <city>Traunstein</city>
        <zip>83278</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mutterhaus der Borromäerinnen</name>
      <address>
        <city>Trier</city>
        <zip>54290</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Barmherzige Brüder Trier</name>
      <address>
        <city>Trier</city>
        <zip>54292</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Tübingen</name>
      <address>
        <city>Tübingen</city>
        <zip>72076</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Ulm</name>
      <address>
        <city>Ulm</city>
        <zip>89081</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>February 2018</verification_date>
  <study_first_submitted>July 22, 2014</study_first_submitted>
  <study_first_submitted_qc>July 22, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 23, 2014</study_first_posted>
  <last_update_submitted>February 27, 2018</last_update_submitted>
  <last_update_submitted_qc>February 27, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">February 28, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Ulm</investigator_affiliation>
    <investigator_full_name>Prof. Dr. Hartmut Doehner</investigator_full_name>
    <investigator_title>Prof. Dr.</investigator_title>
  </responsible_party>
  <keyword>Acute Myeloid Leukemia (AML)</keyword>
  <keyword>Volasertib</keyword>
  <keyword>High-risk Myelodysplastic Syndrome (MDS)</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>
    <mesh_term>Preleukemia</mesh_term>
    <mesh_term>Myelodysplastic Syndromes</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cytarabine</mesh_term>
    <mesh_term>Daunorubicin</mesh_term>
    <mesh_term>Mitoxantrone</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/NCT02198482
org study id: AMLSG 20-13
secondary id: 2014-000477-39
nct id: NCT02198482
lead sponsor: 
has dmc: Yes
Randomized Phase II Trial of Intensive Chemotherapy With or Without Volasertib (BI 6727) in
      Patients With Newly Diagnosed High-Risk Myelodysplastic Syndrome (MDS) and Acute Myeloid
      Leukemia (AML)
The trial is a randomized, Phase II, open label multi-center trial in adult patients with
      newly diagnosed AML or high-risk MDS as defined in the inclusion/exclusion criteria.

      An initial safety run-in study will be performed administering intensive induction therapy
      consisting of daunorubicin and cytarabine with the study drug volasertib administered prior
      or after chemotherapy, as well as consolidation therapy consisting of intermediate-dose
      cytarabine with the study drug volasertib administered prior or after chemotherapy. After
      establishing the volasertib dose, the randomized Phase II portion of the trial will begin:

      Patients will be equally randomized to DA (daunorubicin, cytarabine), V-DA (volasertib
      administered prior to daunorubicin, cytarabine), and DA-V (volasertib administered after
      daunorubicin, cytarabine). All patients will receive a second induction cycle with reduced
      daunorubicin and cytarabine doses. Patients refractory to the first induction cycle and
      patients not achieving a CR/CRi after two induction cycles will be off-study and followed up.

      Patients in CR/CRi after induction therapy will proceed to consolidation therapy.
      Consolidation will be stratified based on the genetic risk profile (according to ELN
      criteria) and patient-related factors (e.g., age, HCT-CI, comorbidities, patient wish).
      Patients with a favorable genetic risk profile and those patients considered ineligible for
      allogeneic HCT will receive repetitive cycles of consolidation according to initial
      randomization, either MiDAC, V-MiDAC (volasertib administered prior to cytarabine), or
      MiDAC-V (volasertib administered after cytarabine). All other patients are assigned to
      allogeneic HCT.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Rate of complete remission (CR) and CR with incomplete blood count recovery (CRi)
time frame: 2 months
measure: Cumulative incidence of relapse
time frame: 4 years
measure: Cumulative incidence of death
time frame: 4 years
measure: Relapse-free survival
time frame: 4 years
measure: Event-free survival
time frame: 4 years
measure: Overall survival
time frame: 4 years
measure: Incidence and intensity of adverse events
time frame: 8 months
arm group label: Daunorubicin, Cytarabine (DA)
arm group type: Active Comparator
description: DA
Induction I:
Daunorubicin 60 mg/m² i.v., d 1-3
Cytarabine 100 mg/m² cont. i.v., d 1-7
Induction II:
Daunorubicin 50 mg/m² i.v. d 1-3
Cytarabine 100 mg/m² cont. i.v., d 1-5
Consolidation therapy:
Patients with genetic favourable risk and those patients not eligible for allogeneic HSCT due to comorbidities, high HCT-CI or patient wish will proceed to 3 cycles of age-adapted consolidation therapy with mitoxantrone and intermediate-dose cytarabine (MiDAC).
Mitoxantrone Younger adults (18 to 60 yrs): 10 mg/m2 by i.v. on day 1. Elderly patients (>60 yrs): 8 mg/m2 by i.v. infusion on day 1.
Intermediate-dose cytarabine:
Younger adults (18 to 60 yrs): 1500 mg/m2 q12h on days 1-3 Elderly patients (>60 yrs): 1000 mg/m2 q12h on days 1-3 An allogeneic HSCT is intended for patients with intermediate I/II and adverse-risk genetics. Optionally, one cycle of consolidation with MiDAC may be given prior to alloHSCT.
arm group label: Volasertib, Daunorubicin, Cytarabine
arm group type: Experimental
description: VDA
Induction I
Volasertib i.v., d1
Daunorubicin 60 mg/m² i.v., d 2-4
Cytarabine 100 mg/m² cont. i.v., d 2-8 Induction II
Volasertib i.v., d1
Daunorubicin 50 mg/m² i.v. d 2-4
Cytarabine 100 mg/m² cont. i.v., d 2-6
Consolidation therapy:
Patients with genetic favourable risk and those patients not eligible for allogeneic HSCT will proceed to 3 cycles of age-adapted consolidation therapy with mitoxantrone and intermediate-dose cytarabine in combination with Volasertib (V-MiDAC).
Volasertib i.v., d1
Mitoxantrone Younger adults (18 to 60 yrs): 10 mg/m2 by i.v. on day 2. Elderly patients (>60 yrs): 8 mg/m2 by i.v. on day 2.
Intermediate-dose cytarabine:
Younger adults (18 to 60 yrs): 1500 mg/m2 q12h on days 2-4 Elderly patients (>60 yrs): 1000 mg/m2 q12h on days 2-4 An allogeneic HSCT is intended for patients with intermediate I/II and adverse-risk genetics. Optionally, one cycle of consolidation with V-MiDAC may be given prior to alloHSCT.
arm group label: Daunorubicin, Cytarabine, Volasertib
arm group type: Experimental
description: DAV
Induction I
Volasertib i.v., d7
Daunorubicin 60 mg/m² i.v., d 1-3
Cytarabine 100 mg/m² i.v., d 1-7 Induction II
Volasertib i.v., d5
Daunorubicin 50 mg/m² i.v. d 1-3
Cytarabine 100 mg/m² cont. i.v., d 1-5
Consolidation therapy:
Patients with genetic fav. risk and those patients not eligible for alloHSCT will proceed to 3 cycles of age-adapted consolidation therapy with mitoxantrone and intermediate-dose cytarabine in combination with Volasertib (MiDAC-V).
Volasertib i.v., d4
Mitoxantrone Younger adults (18 to 60 yrs): 10 mg/m2 by i.v. on day 1. Elderly patients (>60 yrs): 8 mg/m2 by i.v. on day 1.
Intermediate-dose cytarabine:
Younger adults (18 to 60 yrs): 1500 mg/m2 q12h on days 1-3 Elderly patients (>60 yrs): 1000 mg/m2 q12h on days 1-3 An allogeneic HSCT is intended for patients with intermediate I/II and adverse-risk genetics. Optionally, one cycle of consolidation with MiDAC-V may be given prior to alloHSCT.
intervention type: Drug
intervention name: Volasertib
arm group label: Daunorubicin, Cytarabine, Volasertib
arm group label: Volasertib, Daunorubicin, Cytarabine
intervention type: Drug
intervention name: Cytarabine
arm group label: Daunorubicin, Cytarabine (DA)
arm group label: Daunorubicin, Cytarabine, Volasertib
arm group label: Volasertib, Daunorubicin, Cytarabine
other name: ARA-cell
intervention type: Drug
intervention name: Daunorubicin
arm group label: Daunorubicin, Cytarabine (DA)
arm group label: Daunorubicin, Cytarabine, Volasertib
arm group label: Volasertib, Daunorubicin, Cytarabine
other name: Daunoplastin
intervention type: Drug
intervention name: Mitoxantrone
arm group label: Daunorubicin, Cytarabine (DA)
arm group label: Daunorubicin, Cytarabine, Volasertib
arm group label: Volasertib, Daunorubicin, Cytarabine
other name: Novantron
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Hartmut Döhner, Prof. Dr.
role: Principal Investigator
affiliation: AMLSG Clinical Trials Office
last name: Peter Paschka, MD
role: Study Chair
affiliation: University Hospital Ulm
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country: Germany
responsible party type: Principal Investigator
investigator affiliation: University of Ulm
investigator full name: Prof. Dr. Hartmut Doehner
investigator title: Prof. Dr.
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute
mesh term: Preleukemia
mesh term: Myelodysplastic Syndromes
mesh term: Syndrome
mesh term: Cytarabine
mesh term: Daunorubicin
mesh term: Mitoxantrone