<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/NCT03836209</url>
  </required_header>
  <id_info>
    <org_study_id>PrE0905</org_study_id>
    <nct_id>NCT03836209</nct_id>
  </id_info>
  <brief_title>Gilteritinib vs Midostaurin in FLT3 Mutated Acute Myeloid Leukemia</brief_title>
  <official_title>Randomized Trial of Gilteritinib vs Midostaurin in FLT3 Mutated Acute Myeloid Leukemia (AML)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>PrECOG, LLC.</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Astellas Pharma Inc</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>PrECOG, LLC.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Eligible untreated patients with FLT3 acute myeloid leukemia (AML) between the ages of 18 and&#xD;
      70 will be randomized to receive gilteritinib or midostaurin during induction and&#xD;
      consolidation. Patients will also receive standard chemotherapy of daunorubicin and&#xD;
      cytarabine during induction and high-dose cytarabine during consolidation.&#xD;
&#xD;
      Gilteritinib, is an oral drug that works by stopping the leukemia cells from making the FLT3&#xD;
      protein. This may help stop the leukemia cells from growing faster and thus may help make&#xD;
      chemotherapy more effective. Gilteritinib has been approved by the Food and Drug&#xD;
      Administration (FDA) for patients who have relapsed or refractory AML with a FLT3 mutation&#xD;
      but is not approved by the FDA for newly diagnosed FLT3 AML, and its use in this setting is&#xD;
      considered investigational.&#xD;
&#xD;
      Midostaurin is an oral drug that works by blocking several proteins on cancer cells,&#xD;
      including FLT3 that can help leukemia cells grow. Blocking this pathway can cause death to&#xD;
      the leukemic cells. Midostaurin is approved by the FDA for the treatment of FLT3 AML.&#xD;
&#xD;
      The purpose of this study is to compare the effectiveness of gilteritinib to midostaurin in&#xD;
      patients receiving combination chemotherapy for FLT3 AML.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Approximately one third of patients with AML have a particular change in their leukemia cells&#xD;
      (called a mutation) in a gene called FLT3. The presence of a FLT3 mutation can be used to&#xD;
      direct treatment options.&#xD;
&#xD;
      This is an open-label phase II study. Patients will receive standard chemotherapy of&#xD;
      daunorubicin and cytarabine during Induction and high-dose cytarabine during Consolidation.&#xD;
      Patients will be randomized to gilteritinib or midostaurin. After approximately 90 patient's&#xD;
      complete treatment, a review of the effectiveness of gliteritinib compared to midostaurin&#xD;
      will be done. If gilteritinib is not as effective as midostaurin, the study may be stopped.&#xD;
&#xD;
      Bone marrow aspirate and biopsy will be done on Day 21 after start of Induction and after&#xD;
      Induction to assess response. Patients with a complete response may proceed to consolidation&#xD;
      chemotherapy. Another bone marrow aspirate and biopsy will be done after the first cycle of&#xD;
      consolidation is complete.&#xD;
&#xD;
      Mandatory prescreening bone marrow and/or blood samples are required for FLT3 testing. Any&#xD;
      left-over samples will be requested for future research (optional).&#xD;
&#xD;
      Mandatory bone marrow samples for research are required after Induction and if patient&#xD;
      receives Consolidation, after the first cycle of Consolidation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">December 6, 2019</start_date>
  <completion_date type="Anticipated">December 2024</completion_date>
  <primary_completion_date type="Anticipated">October 2023</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>
    <intervention_model_description>Open-Label, Randomized trial of Daunorubicin/Cytarabine and High Dose Cytarabine + Gilteritinib vs Midostaurin for Induction and Consolidation. FLT3 mutated patients will be stratified based on TKD vs ITD. Patients who are FLT3 ITD will be further stratified by Signal Ratio (high vs. low of FLT3 Wild Type) and Nucleophosmin 1-Mutated (NPM1) [positive vs negative].</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>FLT3 Mutation Negative Composite Complete Response (CRc) [includes Complete Response (CR) or CR with incomplete hematologic recovery (CRi)] at end of Induction</measure>
    <time_frame>3 months</time_frame>
    <description>CRc evaluated by polymerase chain reaction (PCR) at the end of Induction</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>FLT3 mutation negative Complete Response (CR) rate at end of Induction</measure>
    <time_frame>3 months</time_frame>
    <description>CR evaluated by FLT3 testing after Induction</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minimal Residual Disease (MRD)- CRc rate at end of Induction</measure>
    <time_frame>3 months</time_frame>
    <description>MRD- CRc evaluated by flow cytometry after Induction</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CRc (CR or CRi) rate at end of Induction</measure>
    <time_frame>3 months</time_frame>
    <description>CRc assessed in accordance with 2017 European LeukemiaNet (ELN)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Event Free Survival (EFS)</measure>
    <time_frame>68 months</time_frame>
    <description>EFS assessed in accordance with 2017 ELN</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>68 months</time_frame>
    <description>OS assessed in accordance with 2017 ELN</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants treatment-related adverse events on Arm A (gilteritinib) as assessed by CTCAE v5.0</measure>
    <time_frame>10 months</time_frame>
    <description>Number of participants with abnormal laboratory values and/or adverse events</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants treatment-related adverse events on Arm B (midostaurin) as assessed by CTCAE v5.0</measure>
    <time_frame>10 months</time_frame>
    <description>Number of participants with abnormal laboratory values and/or adverse events</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">181</enrollment>
  <condition>Acute Myeloid Leukemia</condition>
  <arm_group>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Induction: Daunorubicin, cytarabine and gilteritinib. Depending on response, second cycle of Induction may be given.&#xD;
Consolidation: High-dose cytarabine and gilteritinib.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Induction: Daunorubicin, cytarabine and midostaurin. Depending on response, second cycle of Induction may be given.&#xD;
Consolidation: High-dose cytarabine and midostaurin.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gilteritinib</intervention_name>
    <description>Induction: 120 mg orally daily x 14 days starting on day 8&#xD;
Consolidation: 120 mg orally daily x 14 days starting on day 8 of each cycle (up to 4 cycles)</description>
    <arm_group_label>Arm A</arm_group_label>
    <other_name>ASP2215</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Midostaurin</intervention_name>
    <description>Induction: 50 mg orally twice daily x 14 days beginning on day 8&#xD;
Consolidation: 50 mg orally twice daily x 14 days beginning on day 8 of each cycle (up to 4 cycles)</description>
    <arm_group_label>Arm B</arm_group_label>
    <other_name>RYDAPT</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Daunorubicin</intervention_name>
    <description>First Induction: Daunorubicin 90 mg/m²/day IV Days 1,2,3&#xD;
Second Induction, if needed: Daunorubicin 45 mg/m²/day IV Days 1,2,3</description>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_label>Arm B</arm_group_label>
    <other_name>Daunorubicin hydrochloride</other_name>
    <other_name>Daunomycin</other_name>
    <other_name>Rubidomycin</other_name>
    <other_name>Cerubidine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cytarabine</intervention_name>
    <description>Induction: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1&#xD;
Second Induction, if needed: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1&#xD;
Consolidation: Cytarabine 3 g/m² (recommend 1.5 g/m² for age ≥ 55 or patients with decreased creatinine clearance) every 12 hours IV Days 1,3,5 or Days 1-3 for 6 doses for up to 4 cycles</description>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_label>Arm B</arm_group_label>
    <other_name>Cytosar-U</other_name>
    <other_name>Ara-C</other_name>
    <other_name>Arabinosyl</other_name>
    <other_name>Cytosine Arabinoside</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Registration Criteria:&#xD;
&#xD;
          -  Any patient undergoing bone marrow biopsy with suspicion of or known diagnosis of&#xD;
             acute myeloid leukemia (AML) will be asked to sign a Prescreening Consent to allow for&#xD;
             centralized testing of bone marrow/peripheral blood samples.&#xD;
&#xD;
        Randomization Eligibility Criteria:&#xD;
&#xD;
          -  Patient must have previously untreated FLT3 mutated Non M3 AML (FLT3-TKD or FLT3-ITD&#xD;
             allowed).&#xD;
&#xD;
             ° Standard of care induction 7+3 chemotherapy may start prior to randomization using&#xD;
             same regimen and doses as defined in the protocol while awaiting prescreening test&#xD;
             results.&#xD;
&#xD;
          -  Patient must have had no prior systemic therapy for AML, except as noted below:&#xD;
&#xD;
               -  Hydroxyurea and emergent leukapheresis or preemptive treatment with retinoic acid&#xD;
                  prior to exclusion of Acute Promyelocytic Leukemia (APL) allowed.&#xD;
&#xD;
               -  Prior therapy for myelodysplastic syndrome (MDS) or myeloproliferative neoplasms&#xD;
                  (MPN) (e.g., thalidomide or lenalidomide, interferon, jakafi, cytokines,&#xD;
                  5-azacytidine or decitabine, histone deacetylase inhibitors).&#xD;
&#xD;
               -  Initiation of standard of care 7+3 induction chemotherapy using same regimen and&#xD;
                  doses as defined in protocol while awaiting prescreening test results&#xD;
&#xD;
          -  Patient may not have received hypomethylating agent within 21 days.&#xD;
&#xD;
          -  Patient may not have M3 AML.&#xD;
&#xD;
          -  Patient may not have AML with known Core Binding Factor -t(8;21), inv(16), t(16;16).&#xD;
&#xD;
          -  Patient may not have known active Central Nervous System (CNS) leukemia.&#xD;
&#xD;
             ° Prophylaxis with intrathecal chemotherapy is allowed prior to or during&#xD;
             induction/consolidation.&#xD;
&#xD;
          -  Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of&#xD;
             0-3.&#xD;
&#xD;
          -  Patient must be age ≥ 18 years to ≤ 70 years.&#xD;
&#xD;
          -  Patient must be able to understand and willing to sign Institutional Review Board&#xD;
             (IRB)-approved informed consent.&#xD;
&#xD;
          -  Patient must be willing to provide mandatory bone marrow and blood samples for&#xD;
             research.&#xD;
&#xD;
          -  Patient must have adequate organ function as measured by the following criteria,&#xD;
             obtained ≤ 48 hours prior to randomization except ECG and left ventricular ejection&#xD;
             fraction (LVEF) which can be done ≤ 2 weeks prior to randomization:&#xD;
&#xD;
               -  Serum creatinine ≤ 1.5x institutional upper limit of normal (ULN), or if serum&#xD;
                  creatinine outside normal range, then glomerular filtration rate (GFR) &gt;40 mL/min&#xD;
                  as measured by Cockcroft-Gault formula.&#xD;
&#xD;
               -  Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 3x ULN,&#xD;
                  unless secondary to leukemia.&#xD;
&#xD;
               -  Serum total or direct bilirubin &lt;2 mg/dL, unless due to Gilbert's, hemolysis or&#xD;
                  leukemic infiltration.&#xD;
&#xD;
               -  Fridericia-Corrected QT Interval (QTcF) interval ≤ 500 msec (using Friderica's&#xD;
                  correction).&#xD;
&#xD;
               -  Left Ventricular Ejection Fraction &gt;45%.&#xD;
&#xD;
          -  The patient may not be known to have hypokalemia and/or hypomagnesemia that does not&#xD;
             respond to supplementation.&#xD;
&#xD;
          -  A female patient is eligible to participate if she is not pregnant and at least one of&#xD;
             the following conditions apply:&#xD;
&#xD;
               -  Not a woman of childbearing potential (WOCBP) OR&#xD;
&#xD;
               -  WOCBP who agrees to follow the contraceptive guidance throughout the treatment&#xD;
                  period and for at least 180 days after the final study drug administration.&#xD;
&#xD;
          -  Female patient must agree not to breastfeed or donate ova starting at treatment and&#xD;
             throughout the study period, and for at least 180 days after the final study drug&#xD;
             administration.&#xD;
&#xD;
          -  A male patient must agree not to donate sperm starting at treatment and throughout the&#xD;
             study period, and for at least 120 days after the final study drug administration.&#xD;
&#xD;
          -  A male patient with female partner(s) of child-bearing potential must agree to use&#xD;
             contraception during the treatment period, and for at least 120 days after the final&#xD;
             study drug administration.&#xD;
&#xD;
          -  Male patient with a pregnant or breastfeeding partner(s) must agree to remain&#xD;
             abstinent or use a condom for the duration of the pregnancy or time partner is&#xD;
             breastfeeding throughout the treatment period, and for at least 120 days after the&#xD;
             final study drug administration.&#xD;
&#xD;
          -  Patient may not have another malignancy that could interfere with the evaluation of&#xD;
             safety or efficacy of this combination.&#xD;
&#xD;
          -  Patient may not have a history of Long QT Syndrome.&#xD;
&#xD;
          -  Patient may not have evidence of uncontrolled angina, severe uncontrolled ventricular&#xD;
             arrhythmias, electrocardiographic evidence of acute ischemia, or congestive heart&#xD;
             failure (CHF) New York Heart Association (NYHA) Class 3 or 4. Patient may also not&#xD;
             have a history of CHF NYHA Class 3 or 4 in the past, unless a prescreening&#xD;
             echocardiogram (ECHO) or multigated acquisition scan (MUGA) performed within 2 weeks&#xD;
             prior to study entry with results of left ventricular ejection fraction &gt;45%.&#xD;
&#xD;
          -  Patient may not have had major surgery or radiation therapy within 4 weeks of&#xD;
             registration.&#xD;
&#xD;
          -  Patient may not require treatment with concomitant drugs that are strong inducers of&#xD;
             CYP3A and P-gp.&#xD;
&#xD;
          -  Patient with a known allergy to any of the study medications, their analogues, or&#xD;
             excipients in the various formulations of any agent are not eligible.&#xD;
&#xD;
          -  Patient with known gastrointestinal (GI) disease or prior GI procedure that could&#xD;
             interfere with the oral absorption or tolerance of gilteritinib or midostaurin&#xD;
             including difficulty swallowing are not eligible.&#xD;
&#xD;
          -  Patient with any serious medical or psychiatric illness that could, in the&#xD;
             investigator's opinion, potentially interfere with the completion of the treatment&#xD;
             according to the protocol are not eligible.&#xD;
&#xD;
          -  Patient may not participate in any other therapeutic clinical trials, including those&#xD;
             with other investigational agents not included in this trial during treatment on this&#xD;
             study without prior approval from PrECOG.&#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>Selena Luger, MD</last_name>
    <role>Study Chair</role>
    <affiliation>University of Pennsylvania</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>HonorHealth Research Institute</name>
      <address>
        <city>Scottsdale</city>
        <state>Arizona</state>
        <zip>85258</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California, San Francisco-Fresno (University Oncology Associates)</name>
      <address>
        <city>Clovis</city>
        <state>California</state>
        <zip>93611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCLA</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente Oakland</name>
      <address>
        <city>Oakland</city>
        <state>California</state>
        <zip>94611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UC Irvine Health</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente Roseville</name>
      <address>
        <city>Roseville</city>
        <state>California</state>
        <zip>95661</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente Santa Clara</name>
      <address>
        <city>Santa Clara</city>
        <state>California</state>
        <zip>94115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic- Jacksonville, FL</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Augusta University Medical Center</name>
      <address>
        <city>Augusta</city>
        <state>Georgia</state>
        <zip>30912</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Chicago Medical Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60451</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern University Feinberg School of Medicine</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Franciscan Health Indianapolis</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46237</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kentucky Markey Cancer Center</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40536</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ochsner Clinic Foundation</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70121</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins University</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tufts Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Joseph's Mercy Hospital</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic- Rochester, MN</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Nebraska Medical Center</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Atlantic Health Systems/Morristown Medical Center</name>
      <address>
        <city>Morristown</city>
        <state>New Jersey</state>
        <zip>07962</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwell Health</name>
      <address>
        <city>Lake Success</city>
        <state>New York</state>
        <zip>11042</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mount Sinai</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Weill Cornell Medicine New York Presbyterian Hospital</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Rochester Medical Center</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14642</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SUNY Upstate Medical University</name>
      <address>
        <city>Syracuse</city>
        <state>New York</state>
        <zip>13210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>East Carolina University</name>
      <address>
        <city>Greenville</city>
        <state>North Carolina</state>
        <zip>27834</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Cincinnati Medical Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45267</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospitals Cleveland Medical Center</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Oklahoma Stephenson Cancer Center</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Geisinger Medical Center</name>
      <address>
        <city>Danville</city>
        <state>Pennsylvania</state>
        <zip>17822</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Penn State Milton S. Hershey Medical Center</name>
      <address>
        <city>Hershey</city>
        <state>Pennsylvania</state>
        <zip>17033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Thomas Jefferson University</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pittsburgh Medical Center</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>LDS Hospital</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MultiCare</name>
      <address>
        <city>Spokane</city>
        <state>Washington</state>
        <zip>99218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>West Virginia University</name>
      <address>
        <city>Morgantown</city>
        <state>West Virginia</state>
        <zip>26506</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Wisconsin Clinical Science Center</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53792</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Marshfield Medical Center</name>
      <address>
        <city>Marshfield</city>
        <state>Wisconsin</state>
        <zip>54449</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical College of Wisconsin</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UW Cancer Center at ProHealth Care</name>
      <address>
        <city>Waukesha</city>
        <state>Wisconsin</state>
        <zip>53188</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>February 7, 2019</study_first_submitted>
  <study_first_submitted_qc>February 7, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 11, 2019</study_first_posted>
  <last_update_submitted>June 14, 2023</last_update_submitted>
  <last_update_submitted_qc>June 14, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Gilteritinib</keyword>
  <keyword>Midostaurin</keyword>
  <keyword>Daunorubicin</keyword>
  <keyword>Cytarabine</keyword>
  <keyword>FLT3</keyword>
  <keyword>FLT3 Mutation</keyword>
  <keyword>FLT3 Internal Tandem Duplication (ITD)</keyword>
  <keyword>FLT3 ITD</keyword>
  <keyword>FLT3 Tyrosine Kinase Domain (TKD)</keyword>
  <keyword>FLT3 TKD</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>Cytarabine</mesh_term>
    <mesh_term>Daunorubicin</mesh_term>
    <mesh_term>Midostaurin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Data is proprietary.</ipd_description>
  </patient_data>
  <!-- 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/NCT03836209
org study id: PrE0905
nct id: NCT03836209
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Eligible untreated patients with FLT3 acute myeloid leukemia (AML) between the ages of 18 and
      70 will be randomized to receive gilteritinib or midostaurin during induction and
      consolidation. Patients will also receive standard chemotherapy of daunorubicin and
      cytarabine during induction and high-dose cytarabine during consolidation.

      Gilteritinib, is an oral drug that works by stopping the leukemia cells from making the FLT3
      protein. This may help stop the leukemia cells from growing faster and thus may help make
      chemotherapy more effective. Gilteritinib has been approved by the Food and Drug
      Administration (FDA) for patients who have relapsed or refractory AML with a FLT3 mutation
      but is not approved by the FDA for newly diagnosed FLT3 AML, and its use in this setting is
      considered investigational.

      Midostaurin is an oral drug that works by blocking several proteins on cancer cells,
      including FLT3 that can help leukemia cells grow. Blocking this pathway can cause death to
      the leukemic cells. Midostaurin is approved by the FDA for the treatment of FLT3 AML.

      The purpose of this study is to compare the effectiveness of gilteritinib to midostaurin in
      patients receiving combination chemotherapy for FLT3 AML.
Approximately one third of patients with AML have a particular change in their leukemia cells
      (called a mutation) in a gene called FLT3. The presence of a FLT3 mutation can be used to
      direct treatment options.

      This is an open-label phase II study. Patients will receive standard chemotherapy of
      daunorubicin and cytarabine during Induction and high-dose cytarabine during Consolidation.
      Patients will be randomized to gilteritinib or midostaurin. After approximately 90 patient's
      complete treatment, a review of the effectiveness of gliteritinib compared to midostaurin
      will be done. If gilteritinib is not as effective as midostaurin, the study may be stopped.

      Bone marrow aspirate and biopsy will be done on Day 21 after start of Induction and after
      Induction to assess response. Patients with a complete response may proceed to consolidation
      chemotherapy. Another bone marrow aspirate and biopsy will be done after the first cycle of
      consolidation is complete.

      Mandatory prescreening bone marrow and/or blood samples are required for FLT3 testing. Any
      left-over samples will be requested for future research (optional).

      Mandatory bone marrow samples for research are required after Induction and if patient
      receives Consolidation, after the first cycle of Consolidation.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Open-Label, Randomized trial of Daunorubicin/Cytarabine and High Dose Cytarabine + Gilteritinib vs Midostaurin for Induction and Consolidation. FLT3 mutated patients will be stratified based on TKD vs ITD. Patients who are FLT3 ITD will be further stratified by Signal Ratio (high vs. low of FLT3 Wild Type) and Nucleophosmin 1-Mutated (NPM1) [positive vs negative].
primary purpose: Treatment
masking: None (Open Label)
measure: FLT3 Mutation Negative Composite Complete Response (CRc) [includes Complete Response (CR) or CR with incomplete hematologic recovery (CRi)] at end of Induction
time frame: 3 months
description: CRc evaluated by polymerase chain reaction (PCR) at the end of Induction
measure: FLT3 mutation negative Complete Response (CR) rate at end of Induction
time frame: 3 months
description: CR evaluated by FLT3 testing after Induction
measure: Minimal Residual Disease (MRD)- CRc rate at end of Induction
time frame: 3 months
description: MRD- CRc evaluated by flow cytometry after Induction
measure: CRc (CR or CRi) rate at end of Induction
time frame: 3 months
description: CRc assessed in accordance with 2017 European LeukemiaNet (ELN)
measure: Event Free Survival (EFS)
time frame: 68 months
description: EFS assessed in accordance with 2017 ELN
measure: Overall Survival (OS)
time frame: 68 months
description: OS assessed in accordance with 2017 ELN
measure: Number of participants treatment-related adverse events on Arm A (gilteritinib) as assessed by CTCAE v5.0
time frame: 10 months
description: Number of participants with abnormal laboratory values and/or adverse events
measure: Number of participants treatment-related adverse events on Arm B (midostaurin) as assessed by CTCAE v5.0
time frame: 10 months
description: Number of participants with abnormal laboratory values and/or adverse events
arm group label: Arm A
arm group type: Experimental
description: Induction: Daunorubicin, cytarabine and gilteritinib. Depending on response, second cycle of Induction may be given.
Consolidation: High-dose cytarabine and gilteritinib.
arm group label: Arm B
arm group type: Active Comparator
description: Induction: Daunorubicin, cytarabine and midostaurin. Depending on response, second cycle of Induction may be given.
Consolidation: High-dose cytarabine and midostaurin.
intervention type: Drug
intervention name: Gilteritinib
description: Induction: 120 mg orally daily x 14 days starting on day 8
Consolidation: 120 mg orally daily x 14 days starting on day 8 of each cycle (up to 4 cycles)
arm group label: Arm A
other name: ASP2215
intervention type: Drug
intervention name: Midostaurin
description: Induction: 50 mg orally twice daily x 14 days beginning on day 8
Consolidation: 50 mg orally twice daily x 14 days beginning on day 8 of each cycle (up to 4 cycles)
arm group label: Arm B
other name: RYDAPT
intervention type: Drug
intervention name: Daunorubicin
description: First Induction: Daunorubicin 90 mg/m²/day IV Days 1,2,3
Second Induction, if needed: Daunorubicin 45 mg/m²/day IV Days 1,2,3
arm group label: Arm A
arm group label: Arm B
other name: Daunorubicin hydrochloride
other name: Daunomycin
other name: Rubidomycin
other name: Cerubidine
intervention type: Drug
intervention name: Cytarabine
description: Induction: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1
Second Induction, if needed: Cytarabine 100 mg/m²/day continuous infusion x 7 days starting Day 1
Consolidation: Cytarabine 3 g/m² (recommend 1.5 g/m² for age ≥ 55 or patients with decreased creatinine clearance) every 12 hours IV Days 1,3,5 or Days 1-3 for 6 doses for up to 4 cycles
arm group label: Arm A
arm group label: Arm B
other name: Cytosar-U
other name: Ara-C
other name: Arabinosyl
other name: Cytosine Arabinoside
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Selena Luger, MD
role: Study Chair
affiliation: University of Pennsylvania
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country: United States
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute
mesh term: Cytarabine
mesh term: Daunorubicin
mesh term: Midostaurin
sharing ipd: No
ipd description: Data is proprietary.