<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/NCT02196857</url>
  </required_header>
  <id_info>
    <org_study_id>2014-0076</org_study_id>
    <secondary_id>NCI-2014-01702</secondary_id>
    <nct_id>NCT02196857</nct_id>
  </id_info>
  <brief_title>Sorafenib Plus 5-Azacitidine Initial Therapy of Patients With Acute Myeloid Leukemia (AML) and High Risk Myelodysplastic Syndrome (MS) With FLT3-ITD Mutation</brief_title>
  <official_title>Phase II Study of Sorafenib Plus 5-Azacitidine for the Initial Therapy of Patients With Acute Myeloid Leukemia and High Risk Myelodysplastic Syndrome With FLT3-ITD Mutation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>M.D. Anderson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bayer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>M.D. Anderson Cancer Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The goal of this clinical research study is to learn if 5-azacitidine and sorafenib can help&#xD;
      to control the disease in patients with Acute Myeloid Leukemia (AML) and high risk&#xD;
      Myelodisplastic Syndrome (MDS) with FLT3-ITD mutation. The safety of this drug combination&#xD;
      will also be studied.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study Drug Administration:&#xD;
&#xD;
      If you are found to be eligible to take part in this study, you will receive 5-azacitidine&#xD;
      either as an injection under the skin or by vein on Days 1-7 of each 28-day cycle. If by&#xD;
      vein, the infusion will take about 10-40 minutes.&#xD;
&#xD;
      You will take sorafenib by mouth 2 times a day about 12 hours apart, with at least 1 cup (8&#xD;
      ounces) of water on an empty stomach, every day. If you vomit a dose, do not make it up. You&#xD;
      should wait and take your next scheduled dose.&#xD;
&#xD;
      Each study cycle may last a little longer than 28 days, depending on how you are doing.&#xD;
&#xD;
      Study Visits:&#xD;
&#xD;
      Each week, blood (about 1 tablespoon) will be drawn for routine tests.&#xD;
&#xD;
      Each week for the first 6 weeks, and then as often as your doctor thinks it is needed, you&#xD;
      will have your blood pressure measured.&#xD;
&#xD;
      Before each cycle, you will have a physical exam.&#xD;
&#xD;
      Before every 2-4 cycles, you will have a bone marrow aspirate to check the status of the&#xD;
      disease.&#xD;
&#xD;
      Length of Study:&#xD;
&#xD;
      You may continue taking the study drugs for as long as your doctor thinks it is in your best&#xD;
      interest. You will no longer be able to take the study drugs if the disease gets worse or&#xD;
      intolerable side effects occur, or if you are unable to follow study directions.&#xD;
&#xD;
      Your participation on the study will be over after the follow-up visits.&#xD;
&#xD;
      End-of-Study Visit:&#xD;
&#xD;
      After you have stopped taking the study drugs, the following tests and procedures will be&#xD;
      performed:&#xD;
&#xD;
        -  You will have a physical exam.&#xD;
&#xD;
        -  You will have a bone marrow aspirate to check the status of disease.&#xD;
&#xD;
        -  Blood (about 2 tablespoons) will be drawn for routine tests.&#xD;
&#xD;
      Follow-Up Visits:&#xD;
&#xD;
      After your end-of-study visit, you will return to the clinic every 3 months and have the&#xD;
      following tests and procedures:&#xD;
&#xD;
        -  You will have a physical exam.&#xD;
&#xD;
        -  Blood (about 2 tablespoons) will be drawn for routine tests.&#xD;
&#xD;
      This is an investigational study. Sorafenib is FDA approved and commercially available for&#xD;
      the treatment of kidney cancer and liver cancer. 5-azacitidine is FDA approved for the&#xD;
      treatment of MDS, but combining it with sorafenib is investigational. The study doctor can&#xD;
      tell you how the study drugs are designed to work.&#xD;
&#xD;
      Up to 52 participants will be enrolled in this study. All will take part at MD Anderson.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 6, 2015</start_date>
  <completion_date type="Actual">November 27, 2018</completion_date>
  <primary_completion_date type="Actual">November 27, 2018</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>Participants With a Response CR + PR + CRi</measure>
    <time_frame>After 3, 28 day cycles</time_frame>
    <description>Criteria for response per the International Working Group for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Complete Response (CR) was defined as &lt;/= 5% blasts in the bone marrow (BM) with peripheral blood (PB) demonstrating greater thatn 1x10^9/L platelets with no detectable extramedullary disease. CR with incomplete recovery of PB counts (CRi) is the above criteria but neutrophil or platelet counts less than the stated values. Partial Response (PR) required all of the hematologic values for a CR but with a reduction of at least 50% in the percentage of blasts to 5% to 25% in the bone marrow aspirate.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Toxicity Profile of Azacytidine and Sorafenib</measure>
    <time_frame>After 3, 28 day cycles</time_frame>
    <description>Severity of toxicities graded according to the NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v4.0. Standard reporting guidelines followed for adverse events. Safety data summarized by category, severity and frequency.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Leukemia</condition>
  <arm_group>
    <arm_group_label>Azacytidine + Sorafenib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Azacitidine 75 mg/m2 administered subcutaneously (SQ) or intravenously (IV) daily for 7 days per 28 day cycle. Sorafenib administered orally at a dose of 400 mg twice daily every day continuously.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Azacytidine</intervention_name>
    <description>75 mg/m2 administered subcutaneously (SQ) or intravenously (IV) on Days 1 - 7 for a 28 day cycle.</description>
    <arm_group_label>Azacytidine + Sorafenib</arm_group_label>
    <other_name>5-Azacytidine</other_name>
    <other_name>5-AZA</other_name>
    <other_name>Vidaza</other_name>
    <other_name>5-AZC</other_name>
    <other_name>AZA-CR</other_name>
    <other_name>Ladakamycin</other_name>
    <other_name>NSC-102816</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sorafenib</intervention_name>
    <description>400 mg by mouth twice daily about 12 hours apart, every day for a 28 day cycle.</description>
    <arm_group_label>Azacytidine + Sorafenib</arm_group_label>
    <other_name>Nexavar</other_name>
    <other_name>BAY 43-9006</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients with untreated AML (&gt; or equal to 20% blasts in bone marrow and/or peripheral&#xD;
             blood) or high risk MDS (&gt; or equal to 10% blasts in bone marrow). A. Patients with&#xD;
             AML and history of MDS who have received prior therapy with a hypomethylating agent&#xD;
             (including azacytidine) and/or with lenalidomide for prior MDS are eligible if the&#xD;
             treating physician feels that participation in the study is in the patients' best&#xD;
             interest. B. Patients should have molecular evidence of the presence of FLT3-ITD&#xD;
             mutation with a molecular burden of at least 10%.&#xD;
&#xD;
          2. Age &gt; or equal to 60 years; patients younger than 60 who are unsuitable for or&#xD;
             unwilling to receive standard cytotoxic chemotherapy are also eligible to be enrolled.&#xD;
&#xD;
          3. Eastern Cooperative Oncology Group (ECOG) Performance Status &lt; or equal 2.&#xD;
&#xD;
          4. Adequate liver (bilirubin &lt; or equal to 1.5 x ULN, Alanine Aminotransferase (ALT) or&#xD;
             Aspartate Aminotransferase (AST) &lt; or equal to 2.5 x ULN and Alkaline phosphatase &lt; or&#xD;
             equal to 4 x ULN if not related to leukemic disease) and renal (creatinine &lt; or equal&#xD;
             to 1.5 x ULN) function.&#xD;
&#xD;
          5. Patients must provide written informed consent.&#xD;
&#xD;
          6. Patients must have been off therapy for MDS for 2 weeks prior to entering this study,&#xD;
             and must have recovered from the toxic effects of that therapy to at least grade 1,&#xD;
             unless there is evidence of rapidly progressive disease. Use of hydroxyurea (any dose)&#xD;
             or ara-C (up to 1 g/m^2 X 2 doses) for patients with rapidly proliferative disease is&#xD;
             allowed before the start of study therapy; these should be stopped for 24 hours prior&#xD;
             to the initiation of azacitidine and sorafenib.&#xD;
&#xD;
          7. Women of childbearing potential should be advised to avoid becoming pregnant with an&#xD;
             adequate method of contraception (barrier or hormonal methods) and men should be&#xD;
             advised to not father a child while receiving treatment with azacitidine. All men and&#xD;
             women of childbearing potential must use acceptable methods of birth control&#xD;
             throughout the study as described below: Women of childbearing potential must have a&#xD;
             negative serum pregnancy test performed within 7 days prior to the start of treatment.&#xD;
             Men should use adequate birth control for at least 30 days after the last&#xD;
             administration of sorafenib. Post-menopausal women (defined as no menses for at least&#xD;
             one year) and surgically sterilized women are not required to undergo a pregnancy&#xD;
             test. Females of childbearing potential: Recommendation is for 2 effective&#xD;
             contraceptive methods during the study.&#xD;
&#xD;
          8. 7. Continued: Adequate forms of contraception are double-barrier methods (condoms with&#xD;
             spermicidal jelly or foam and diaphragm with spermicidal jelly or foam), oral, depo&#xD;
             provera, or injectable contraceptives, intrauterine devices, and tubal ligation. Male&#xD;
             patients with female partners who are of childbearing potential: Recommendation is for&#xD;
             male and partner to use at least 2 effective contraceptive methods, as described&#xD;
             above, during the study.&#xD;
&#xD;
          9. Ability to understand and the willingness to sign a written informed consent. A signed&#xD;
             informed consent must be obtained prior to any study specific procedures.&#xD;
&#xD;
         10. International Normalized Ratio (INR) &lt; or equal to 1.5. Patients receiving&#xD;
             anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to&#xD;
             participate. For patients on warfarin, the INR should be measured prior to initiation&#xD;
             of sorafenib and monitored weekly, or as defined by the local standard of care, until&#xD;
             INR is stable.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Nursing and pregnant females.&#xD;
&#xD;
          2. Patients with acute promyelocytic leukemia are excluded.&#xD;
&#xD;
          3. Patients with known allergy to sorafenib or azacitidine, mannitol or any of their&#xD;
             components.&#xD;
&#xD;
          4. Patients with known severe impairment of gastrointestinal (GI) function or GI disease&#xD;
             that may significantly alter the absorption of sorafenib.&#xD;
&#xD;
          5. Patients with any other known disease (except carcinoma in-situ) or concurrent severe&#xD;
             and/or uncontrolled medical condition (e.g. uncontrolled diabetes, cardiovascular&#xD;
             disease including congestive heart failure, myocardial infarction within 6 months and&#xD;
             uncontrolled hypertension, chronic renal disease (creatinine clearance &lt; 20 ml/min&#xD;
             using the Cockcroft and Gault formula), or active uncontrolled infection) which could&#xD;
             compromise participation in the study.&#xD;
&#xD;
          6. Patients with a known confirmed diagnosis of HIV infection or active viral hepatitis&#xD;
             (B or C).&#xD;
&#xD;
          7. Patients who have had any major surgical procedure within 28 days prior to Day 1.&#xD;
&#xD;
          8. Patients unwilling or unable to comply with the protocol.&#xD;
&#xD;
          9. Cardiac disease: Congestive heart failure &gt; class II New York Heart Association&#xD;
             (NYHA). Patients must not have unstable angina (anginal symptoms at rest) or new onset&#xD;
             angina (began within the last 3 months) or myocardial infarction within the past 6&#xD;
             months.&#xD;
&#xD;
         10. Uncontrolled hypertension defined as systolic blood pressure &gt; 150? mmHg or diastolic&#xD;
             pressure &gt; 90 mmHg, despite optimal medical management.&#xD;
&#xD;
         11. Active clinically serious infection &gt; CTCAE v4, Grade 2 not controlled with&#xD;
             antibiotics.&#xD;
&#xD;
         12. Thrombolic or embolic events such as a cerebrovascular accident including transient&#xD;
             ischemic attacks within the past 6 months.&#xD;
&#xD;
         13. Pulmonary hemorrhage/bleeding event &gt; or equal to CTCAE v4. Grade 2 within 4 weeks of&#xD;
             first dose of study drug.&#xD;
&#xD;
         14. Any other hemorrhage/bleeding event &gt; or equal to CTCAE v4. Grade 3 within 4 weeks of&#xD;
             first dose of study drug.&#xD;
&#xD;
         15. Serious non-healing wound, ulcer, or bone fracture.&#xD;
&#xD;
         16. Evidence of bleeding diathesis or coagulopathy within the past 6 months.&#xD;
&#xD;
         17. Known or suspected allergy to sorafenib or any agent given in the course of this&#xD;
             trial.&#xD;
&#xD;
         18. Substance abuse, medical, psychological or social conditions that may interfere with&#xD;
             the patient's participation in the study or evaluation of the study results including&#xD;
             known non-compliance issues on study trials.&#xD;
&#xD;
         19. Use of strong CYP3A4 inducer.&#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>Farhad Ravandi-Kashani, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>M.D. Anderson Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Texas MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mdanderson.org</url>
    <description>University of Texas MD Anderson Cancer Center Website</description>
  </link>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>July 18, 2014</study_first_submitted>
  <study_first_submitted_qc>July 18, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 22, 2014</study_first_posted>
  <results_first_submitted>December 17, 2019</results_first_submitted>
  <results_first_submitted_qc>December 17, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">January 6, 2020</results_first_posted>
  <last_update_submitted>January 6, 2020</last_update_submitted>
  <last_update_submitted_qc>January 6, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 14, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Leukemia</keyword>
  <keyword>Acute myeloid leukemia</keyword>
  <keyword>AML</keyword>
  <keyword>High risk myelodysplastic syndrome</keyword>
  <keyword>MDS</keyword>
  <keyword>FLT3-ITD mutation</keyword>
  <keyword>Azacytidine</keyword>
  <keyword>5-Azacytidine</keyword>
  <keyword>5-AZA</keyword>
  <keyword>Vidaza</keyword>
  <keyword>5-AZC</keyword>
  <keyword>AZA-CR</keyword>
  <keyword>Ladakamycin</keyword>
  <keyword>NSC-102816</keyword>
  <keyword>Sorafenib</keyword>
  <keyword>Nexavar</keyword>
  <keyword>BAY 43-9006</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>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Azacitidine</mesh_term>
    <mesh_term>Sorafenib</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 9, 2015</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/57/NCT02196857/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Recruitment Period: February 2015 - February 2018</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Azacytidine + Sorafenib</title>
          <description>Azacitidine 75 mg/m2 administered subcutaneously (SQ) or intravenously (IV) daily for 7 days per 28 day cycle. Sorafenib administered orally at a dose of 400 mg twice daily every day continuously.&#xD;
Azacytidine: 75 mg/m2 administered subcutaneously (SQ) or intravenously (IV) on Days 1 - 7 for a 28 day cycle.&#xD;
Sorafenib: 400 mg by mouth twice daily about 12 hours apart, every day for a 28 day cycle.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Azacytidine + Sorafenib</title>
          <description>Azacitidine 75 mg/m2 administered subcutaneously (SQ) or intravenously (IV) daily for 7 days per 28 day cycle. Sorafenib administered orally at a dose of 400 mg twice daily every day continuously.&#xD;
Azacytidine: 75 mg/m2 administered subcutaneously (SQ) or intravenously (IV) on Days 1 - 7 for a 28 day cycle.&#xD;
Sorafenib: 400 mg by mouth twice daily about 12 hours apart, every day for a 28 day cycle.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="16"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="75" lower_limit="67" upper_limit="86"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Participants With a Response CR + PR + CRi</title>
        <description>Criteria for response per the International Working Group for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Complete Response (CR) was defined as &lt;/= 5% blasts in the bone marrow (BM) with peripheral blood (PB) demonstrating greater thatn 1x10^9/L platelets with no detectable extramedullary disease. CR with incomplete recovery of PB counts (CRi) is the above criteria but neutrophil or platelet counts less than the stated values. Partial Response (PR) required all of the hematologic values for a CR but with a reduction of at least 50% in the percentage of blasts to 5% to 25% in the bone marrow aspirate.</description>
        <time_frame>After 3, 28 day cycles</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Azacytidine + Sorafenib</title>
            <description>Azacitidine 75 mg/m2 administered subcutaneously (SQ) or intravenously (IV) daily for 7 days per 28 day cycle. Sorafenib administered orally at a dose of 400 mg twice daily every day continuously.&#xD;
Azacytidine: 75 mg/m2 administered subcutaneously (SQ) or intravenously (IV) on Days 1 - 7 for a 28 day cycle.&#xD;
Sorafenib: 400 mg by mouth twice daily about 12 hours apart, every day for a 28 day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Participants With a Response CR + PR + CRi</title>
          <description>Criteria for response per the International Working Group for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Complete Response (CR) was defined as &lt;/= 5% blasts in the bone marrow (BM) with peripheral blood (PB) demonstrating greater thatn 1x10^9/L platelets with no detectable extramedullary disease. CR with incomplete recovery of PB counts (CRi) is the above criteria but neutrophil or platelet counts less than the stated values. Partial Response (PR) required all of the hematologic values for a CR but with a reduction of at least 50% in the percentage of blasts to 5% to 25% in the bone marrow aspirate.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Complete Response (CR)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Partial Response (PR)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CR with incomplete platelet recovery (CRi)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Toxicity Profile of Azacytidine and Sorafenib</title>
        <description>Severity of toxicities graded according to the NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v4.0. Standard reporting guidelines followed for adverse events. Safety data summarized by category, severity and frequency.</description>
        <time_frame>After 3, 28 day cycles</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Azacytidine + Sorafenib</title>
            <description>Azacitidine 75 mg/m2 administered subcutaneously (SQ) or intravenously (IV) daily for 7 days per 28 day cycle. Sorafenib administered orally at a dose of 400 mg twice daily every day continuously.&#xD;
Azacytidine: 75 mg/m2 administered subcutaneously (SQ) or intravenously (IV) on Days 1 - 7 for a 28 day cycle.&#xD;
Sorafenib: 400 mg by mouth twice daily about 12 hours apart, every day for a 28 day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Toxicity Profile of Azacytidine and Sorafenib</title>
          <description>Severity of toxicities graded according to the NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v4.0. Standard reporting guidelines followed for adverse events. Safety data summarized by category, severity and frequency.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Diarrhea</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dyspnea</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Fatigue</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Febrile Neutropenia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nausea</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Rash/Desquamation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to three years</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Azacytidine + Sorafenib</title>
          <description>Azacitidine 75 mg/m2 administered subcutaneously (SQ) or intravenously (IV) daily for 7 days per 28 day cycle. Sorafenib administered orally at a dose of 400 mg twice daily every day continuously.&#xD;
Azacytidine: 75 mg/m2 administered subcutaneously (SQ) or intravenously (IV) on Days 1 - 7 for a 28 day cycle.&#xD;
Sorafenib: 400 mg by mouth twice daily about 12 hours apart, every day for a 28 day cycle.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac Triponin Increase</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Intracranial Hemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute Heart Failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Intestine Obstruction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Facial Pain/Dental</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Febrile Neutropenia</sub_title>
                <counts group_id="E1" events="8" subjects_affected="5" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Urinary Tract Infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Lung Infection</sub_title>
                <counts group_id="E1" events="12" subjects_affected="5" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Skin Infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Stroke</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute Kidney failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>generalized edema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Acute Respiratory Failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Laryngeal Hemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Laryngeal Inflammation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotnesion</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Watery eye</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Edema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Hemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Febrile Neutropenia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypercalcemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Dyspena</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Ravandi-Kashani,Farhad MD./Professor</name_or_title>
      <organization>The University of Texas MD Anderson Cancer Center</organization>
      <phone>713-745-0394</phone>
      <email>fravandi@mdanderson.org</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02196857
org study id: 2014-0076
secondary id: NCI-2014-01702
nct id: NCT02196857
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The goal of this clinical research study is to learn if 5-azacitidine and sorafenib can help
      to control the disease in patients with Acute Myeloid Leukemia (AML) and high risk
      Myelodisplastic Syndrome (MDS) with FLT3-ITD mutation. The safety of this drug combination
      will also be studied.
Study Drug Administration:

      If you are found to be eligible to take part in this study, you will receive 5-azacitidine
      either as an injection under the skin or by vein on Days 1-7 of each 28-day cycle. If by
      vein, the infusion will take about 10-40 minutes.

      You will take sorafenib by mouth 2 times a day about 12 hours apart, with at least 1 cup (8
      ounces) of water on an empty stomach, every day. If you vomit a dose, do not make it up. You
      should wait and take your next scheduled dose.

      Each study cycle may last a little longer than 28 days, depending on how you are doing.

      Study Visits:

      Each week, blood (about 1 tablespoon) will be drawn for routine tests.

      Each week for the first 6 weeks, and then as often as your doctor thinks it is needed, you
      will have your blood pressure measured.

      Before each cycle, you will have a physical exam.

      Before every 2-4 cycles, you will have a bone marrow aspirate to check the status of the
      disease.

      Length of Study:

      You may continue taking the study drugs for as long as your doctor thinks it is in your best
      interest. You will no longer be able to take the study drugs if the disease gets worse or
      intolerable side effects occur, or if you are unable to follow study directions.

      Your participation on the study will be over after the follow-up visits.

      End-of-Study Visit:

      After you have stopped taking the study drugs, the following tests and procedures will be
      performed:

        -  You will have a physical exam.

        -  You will have a bone marrow aspirate to check the status of disease.

        -  Blood (about 2 tablespoons) will be drawn for routine tests.

      Follow-Up Visits:

      After your end-of-study visit, you will return to the clinic every 3 months and have the
      following tests and procedures:

        -  You will have a physical exam.

        -  Blood (about 2 tablespoons) will be drawn for routine tests.

      This is an investigational study. Sorafenib is FDA approved and commercially available for
      the treatment of kidney cancer and liver cancer. 5-azacitidine is FDA approved for the
      treatment of MDS, but combining it with sorafenib is investigational. The study doctor can
      tell you how the study drugs are designed to work.

      Up to 52 participants will be enrolled in this study. All will take part at MD Anderson.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Participants With a Response CR + PR + CRi
time frame: After 3, 28 day cycles
description: Criteria for response per the International Working Group for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Complete Response (CR) was defined as </= 5% blasts in the bone marrow (BM) with peripheral blood (PB) demonstrating greater thatn 1x10^9/L platelets with no detectable extramedullary disease. CR with incomplete recovery of PB counts (CRi) is the above criteria but neutrophil or platelet counts less than the stated values. Partial Response (PR) required all of the hematologic values for a CR but with a reduction of at least 50% in the percentage of blasts to 5% to 25% in the bone marrow aspirate.
measure: Toxicity Profile of Azacytidine and Sorafenib
time frame: After 3, 28 day cycles
description: Severity of toxicities graded according to the NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v4.0. Standard reporting guidelines followed for adverse events. Safety data summarized by category, severity and frequency.
arm group label: Azacytidine + Sorafenib
arm group type: Experimental
description: Azacitidine 75 mg/m2 administered subcutaneously (SQ) or intravenously (IV) daily for 7 days per 28 day cycle. Sorafenib administered orally at a dose of 400 mg twice daily every day continuously.
intervention type: Drug
intervention name: Azacytidine
description: 75 mg/m2 administered subcutaneously (SQ) or intravenously (IV) on Days 1 - 7 for a 28 day cycle.
arm group label: Azacytidine + Sorafenib
other name: 5-Azacytidine
other name: 5-AZA
other name: Vidaza
other name: 5-AZC
other name: AZA-CR
other name: Ladakamycin
other name: NSC-102816
intervention type: Drug
intervention name: Sorafenib
description: 400 mg by mouth twice daily about 12 hours apart, every day for a 28 day cycle.
arm group label: Azacytidine + Sorafenib
other name: Nexavar
other name: BAY 43-9006
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Farhad Ravandi-Kashani, MD
role: Principal Investigator
affiliation: M.D. Anderson Cancer Center
facility: 
country: United States
url: http://www.mdanderson.org
description: University of Texas MD Anderson Cancer Center Website
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute
mesh term: Preleukemia
mesh term: Myelodysplastic Syndromes
mesh term: Azacitidine
mesh term: Sorafenib
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 