<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/NCT01732445</url>
  </required_header>
  <id_info>
    <org_study_id>MC1283</org_study_id>
    <secondary_id>NCI-2012-02201</secondary_id>
    <secondary_id>MC1283</secondary_id>
    <secondary_id>P30CA015083</secondary_id>
    <nct_id>NCT01732445</nct_id>
  </id_info>
  <brief_title>Ruxolitinib Phosphate and Danazol in Treating Anemia in Patients With Myelofibrosis</brief_title>
  <official_title>A Phase 2 Pilot Trial of Ruxolitinib Combined With Danazol for Patients With Primary Myelofibrosis (MF), Post Essential Thrombocythemia-Myelofibrosis (Post ET) and Post Polycythemia Vera Myelofibrosis (PV MF) Suffering From Anemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mayo Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Mayo Clinic</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase II pilot trial studies how well ruxolitinib phosphate and danazol work in treating&#xD;
      anemia in patients with myelofibrosis. Ruxolitinib phosphate and danazol may cause the body&#xD;
      to make more red blood cells. They are used to treat anemia in patients with myelofibrosis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To evaluate the efficacy (best overall response) of ruxolitinib (ruxolitinib phosphate)&#xD;
      and danazol in patients with myelofibrosis suffering from anemia.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To evaluate the overall survival of patients with myelofibrosis suffering from anemia&#xD;
      initiating ruxolitinib and danazol.&#xD;
&#xD;
      II. To evaluate the adverse event profile of ruxolitinib and danazol in patients with&#xD;
      myelofibrosis suffering from anemia.&#xD;
&#xD;
      TERTIARY OBJECTIVES:&#xD;
&#xD;
      I. To evaluate quality of life (QOL) and patient-reported symptoms using the&#xD;
      Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) and European Organization for&#xD;
      Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) with&#xD;
      ruxolitinib and danazol for patients with myelofibrosis suffering from anemia.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive ruxolitinib phosphate orally (PO) twice daily (BID) and danazol PO thrice&#xD;
      daily (TID) on days 1-56. Treatment repeats every 56 days for 6 courses in the absence of&#xD;
      disease progression or unacceptable toxicity. At the treating physician's discretion,&#xD;
      patients may continue treatment past 6 courses if they are without disease progression.&#xD;
&#xD;
      After completion of study treatment, patients are followed up every 6 months for 2 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 2013</start_date>
  <completion_date type="Actual">August 10, 2017</completion_date>
  <primary_completion_date type="Actual">July 14, 2016</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>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Best Overall Response Rate as Determined by International Working Group Criteria</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Best overall response rate as determined by International Working Group criteria: An evaluable patient will be classified as a responder for the primary endpoint if the patient's best overall response is CR, PR or CI (Clinical Improvement) as determined by International Working Group Criteria over all cycles of study treatment. The percentage of successes will be estimated by the number of successes (defined as complete response, partial response, or clinical improvement) divided by the total number of evaluable patients times 100. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Survival Time</measure>
    <time_frame>From registration to death due to any cause, assessed up to 2 years</time_frame>
    <description>Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier. The median and 95% confidence interval are reported below.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4)</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns within patient groups. In addition, we will review all adverse event data that is graded as 3, 4, or 5 and classified as either &quot;unrelated&quot; or &quot;unlikely to be related&quot; to study treatment in the event of an actual relationship developing. The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Patient-reported Symptoms Assessed Using the MPN-SAF, as Measured by the Percentage of Patients With a Decrease in MPN-SAF TSS Greater Than 50% From Baseline</measure>
    <time_frame>Baseline to up to 2 years</time_frame>
    <description>Patient-reported symptoms will be described at each time point using the mean, confidence interval, median, and range. The Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) will be analyzed using published scoring algorithms. MPN-SAF includes 27 items scored on a scale of 0 to 10. The MPN-SAF Total Symptom Score (TSS) (range 0-100) was computed according to the published scoring algorithm. Higher scores represent worse symptom burden. The percentage of patients with a decrease in MPN-SAF TSS greater than 50% from baseline and 95% confidence interval are reported below.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">14</enrollment>
  <condition>Anemia</condition>
  <condition>Primary Myelofibrosis</condition>
  <condition>Secondary Myelofibrosis</condition>
  <arm_group>
    <arm_group_label>Supportive care (ruxolitinib phosphate and danazol)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive ruxolitinib phosphate PO BID and danazol PO TID on days 1-56. Treatment repeats every 56 days for 6 courses in the absence of disease progression or unacceptable toxicity. At the treating physician's discretion, patients may continue treatment past 6 courses if they are without disease progression.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ruxolitinib phosphate</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Supportive care (ruxolitinib phosphate and danazol)</arm_group_label>
    <other_name>INCB18424</other_name>
    <other_name>Jakafi</other_name>
    <other_name>oral JAK inhibitor INCB18424</other_name>
    <other_name>oral Janus-associated kinase inhibitor INCB18424</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>danazol</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Supportive care (ruxolitinib phosphate and danazol)</arm_group_label>
    <other_name>Chronogyn</other_name>
    <other_name>DAN</other_name>
    <other_name>Danocrine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>quality-of-life assessment</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Supportive care (ruxolitinib phosphate and danazol)</arm_group_label>
    <other_name>quality of life assessment</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>questionnaire administration</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Supportive care (ruxolitinib phosphate and danazol)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histological confirmation of primary myelofibrosis (MF), post polycythemia vera (PV)&#xD;
             or post essential thrombocythemia (ET) myelofibrosis (intermediate 1, intermediate II&#xD;
             or high risk) requiring medical therapy&#xD;
&#xD;
          -  Anemia is required for trial entry (defined as hemoglobin &lt; 10g/dL or transfusion&#xD;
             dependent [having needed a transfusion anytime in the past 6 months])&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 at study&#xD;
             entry&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1000/uL&#xD;
&#xD;
          -  Platelet count &gt;= 50,000/uL&#xD;
&#xD;
          -  Serum creatinine =&lt; 1.5 x the upper limit of normal (ULN)&#xD;
&#xD;
          -  Total bilirubin =&lt; 1.5 x ULN; if total bilirubin is &gt; 1.5 x ULN, a direct bilirubin&#xD;
             should be performed and must be &lt; 1.5mg/dL&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =&lt; 3 x ULN; higher&#xD;
             values (i.e., =&lt; 5 x ULN) are allowed if clinically compatible with hepatic&#xD;
             extramedullary hematopoiesis&#xD;
&#xD;
          -  Life expectancy of &gt;= 6 months&#xD;
&#xD;
          -  Patient able to provide voluntary written informed consent to participate&#xD;
&#xD;
          -  Willing to comply with scheduled visits, treatment plans, laboratory assessments, and&#xD;
             other study-related procedures&#xD;
&#xD;
          -  Negative pregnancy test done =&lt; 7 days prior to registration, for women of&#xD;
             childbearing potential only&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any chemotherapy (e.g., hydroxyurea), immunomodulatory drug therapy (e.g.,&#xD;
             thalidomide, interferon-alpha), immunosuppressive therapy, corticosteroids &gt; 10 mg/day&#xD;
             prednisone or equivalent, or growth factor treatment (e.g., erythropoietin), hormones&#xD;
             (e.g., androgens, danazol) =&lt; 14 days prior to registration; note: patients who are on&#xD;
             ruxolitinib may continue on without a 14 day wash out at the treating physician's&#xD;
             discretion&#xD;
&#xD;
          -  Major surgery =&lt; 28 days or radiation =&lt; 6 months prior to registration&#xD;
&#xD;
          -  Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment&#xD;
             of the investigator, would make the patient inappropriate for entry into this study or&#xD;
             interfere significantly with the proper assessment of safety and toxicity of the&#xD;
             prescribed regimens&#xD;
&#xD;
          -  Active acute infection requiring antibiotics&#xD;
&#xD;
          -  Uncontrolled congestive heart failure (New York Heart Association classification 3 or&#xD;
             4), angina, myocardial infarction, cerebrovascular accident, coronary/peripheral&#xD;
             artery bypass, graft surgery, transient ischemic attack, or pulmonary embolism within&#xD;
             3 months prior to registration&#xD;
&#xD;
          -  Participation in any study of an investigational agent (drug, biologic, device) =&lt; 30&#xD;
             days, unless during non-treatment phase&#xD;
&#xD;
          -  Any of the following:&#xD;
&#xD;
               -  Pregnant women&#xD;
&#xD;
               -  Nursing women&#xD;
&#xD;
               -  Men or women of childbearing potential who are unwilling to employ adequate&#xD;
                  contraception&#xD;
&#xD;
          -  Known human immunodeficiency virus or acquired immunodeficiency syndrome-related&#xD;
             illness&#xD;
&#xD;
          -  Clinically active hepatitis B or C&#xD;
&#xD;
          -  Active malignancy other than MF, except adequately treated basal cell carcinoma and&#xD;
             squamous cell carcinoma of the skin, cervical carcinoma in situ or other malignancies&#xD;
             that have been stable and off therapy for 5 years&#xD;
&#xD;
          -  Patient currently taking simvastatin, or lovastatin at a dose greater than 10 mg/day&#xD;
&#xD;
          -  Men with prostate specific antigen (PSA) &gt; 4 ng/ml or with uncontrolled benign&#xD;
             prostatic hypertrophy&#xD;
&#xD;
          -  Patient received prior combination treatment with ruxolitinib and danazol together;&#xD;
             note: previous treatment with ruxolitinib and/or danazol as single agent therapy is&#xD;
             allowed&#xD;
&#xD;
          -  Receiving any medications or substances that are strong or moderate inhibitors of&#xD;
             cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4); use of the following&#xD;
             strong or moderate inhibitors are prohibited =&lt; 7 days prior to registration&#xD;
&#xD;
               -  Strong inhibitors of CYP3A4:&#xD;
&#xD;
                    -  Indinavir (Crixivan)&#xD;
&#xD;
                    -  Nelfinavir (Viracept)&#xD;
&#xD;
                    -  Atazanavir (Reyataz)&#xD;
&#xD;
                    -  Clarithromycin (Biaxin, Biaxin XL)&#xD;
&#xD;
                    -  Itraconazole (Sporanox)&#xD;
&#xD;
                    -  Ketoconazole (Nizoral)&#xD;
&#xD;
                    -  Nefazodone (Serzone)&#xD;
&#xD;
                    -  Saquinavir (Fortovase, Invirase)&#xD;
&#xD;
                    -  Telithromycin (Ketek)&#xD;
&#xD;
               -  Moderate inhibitors of CYP3A4&#xD;
&#xD;
                    -  Erythromycin (Erythrocin, E.E.S., Ery-Tab, Eryc, EryPed, PCE)&#xD;
&#xD;
                    -  Fluconazole (Diflucan)&#xD;
&#xD;
                    -  Grapefruit juice&#xD;
&#xD;
                    -  Verapamil (Calan, Calan SR, Covera-HS, Isoptin SR, Verelan)&#xD;
&#xD;
                    -  Verelan PM&#xD;
&#xD;
                    -  Diltiazem (Cardizem, Cardizem CD, Cardizem LA, Cardizem SR, Cartia XT,&#xD;
                       Dilacor XR, Diltia XT, Taztia XT, Tiazac)&#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>Ruben Mesa</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic in Arizona</name>
      <address>
        <city>Scottsdale</city>
        <state>Arizona</state>
        <zip>85259</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tisch Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2017</verification_date>
  <study_first_submitted>November 19, 2012</study_first_submitted>
  <study_first_submitted_qc>November 21, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 22, 2012</study_first_posted>
  <results_first_submitted>August 4, 2017</results_first_submitted>
  <results_first_submitted_qc>September 15, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">October 18, 2017</results_first_posted>
  <last_update_submitted>September 15, 2017</last_update_submitted>
  <last_update_submitted_qc>September 15, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 18, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anemia</mesh_term>
    <mesh_term>Primary Myelofibrosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Danazol</mesh_term>
    <mesh_term>Janus Kinase Inhibitors</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Supportive Care (Ruxolitinib Phosphate and Danazol)</title>
          <description>Patients receive ruxolitinib phosphate PO 10 mg BID and danazol PO 200 mg TID on days 1-56. Treatment repeats every 56 days for 6 courses in the absence of disease progression or unacceptable toxicity. At the treating physician's discretion, patients may continue treatment past 6 courses if they are without disease progression.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
              </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>Supportive Care (Ruxolitinib Phosphate and Danazol)</title>
          <description>Patients receive ruxolitinib phosphate PO 10 mg BID and danazol PO 200 mg TID on days 1-56. Treatment repeats every 56 days for 6 courses in the absence of disease progression or unacceptable toxicity. At the treating physician's discretion, patients may continue treatment past 6 courses if they are without disease progression.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="14"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <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="70.5" lower_limit="43" upper_limit="78"/>
                  </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="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Best Overall Response Rate as Determined by International Working Group Criteria</title>
        <description>Best overall response rate as determined by International Working Group criteria: An evaluable patient will be classified as a responder for the primary endpoint if the patient's best overall response is CR, PR or CI (Clinical Improvement) as determined by International Working Group Criteria over all cycles of study treatment. The percentage of successes will be estimated by the number of successes (defined as complete response, partial response, or clinical improvement) divided by the total number of evaluable patients times 100. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.</description>
        <time_frame>Up to 2 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Supportive Care (Ruxolitinib Phosphate and Danazol)</title>
            <description>Patients receive ruxolitinib phosphate PO 10 mg BID and danazol PO 200 mg TID on days 1-56. Treatment repeats every 56 days for 6 courses in the absence of disease progression or unacceptable toxicity. At the treating physician's discretion, patients may continue treatment past 6 courses if they are without disease progression.</description>
          </group>
        </group_list>
        <measure>
          <title>Best Overall Response Rate as Determined by International Working Group Criteria</title>
          <description>Best overall response rate as determined by International Working Group criteria: An evaluable patient will be classified as a responder for the primary endpoint if the patient's best overall response is CR, PR or CI (Clinical Improvement) as determined by International Working Group Criteria over all cycles of study treatment. The percentage of successes will be estimated by the number of successes (defined as complete response, partial response, or clinical improvement) divided by the total number of evaluable patients times 100. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.</description>
          <units>percentage of patients with CR, PR or CI</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28.6" lower_limit="8.4" upper_limit="58.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Survival Time</title>
        <description>Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier. The median and 95% confidence interval are reported below.</description>
        <time_frame>From registration to death due to any cause, assessed up to 2 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Supportive Care (Ruxolitinib Phosphate and Danazol)</title>
            <description>Patients receive ruxolitinib phosphate PO 10 mg BID and danazol PO 200 mg TID on days 1-56. Treatment repeats every 56 days for 6 courses in the absence of disease progression or unacceptable toxicity. At the treating physician's discretion, patients may continue treatment past 6 courses if they are without disease progression.</description>
          </group>
        </group_list>
        <measure>
          <title>Survival Time</title>
          <description>Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier. The median and 95% confidence interval are reported below.</description>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.2" lower_limit="4.1" upper_limit="28.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4)</title>
        <description>The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns within patient groups. In addition, we will review all adverse event data that is graded as 3, 4, or 5 and classified as either &quot;unrelated&quot; or &quot;unlikely to be related&quot; to study treatment in the event of an actual relationship developing. The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below.</description>
        <time_frame>Up to 2 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Supportive Care (Ruxolitinib Phosphate and Danazol)</title>
            <description>Patients receive ruxolitinib phosphate PO 10 mg BID and danazol PO 200 mg TID on days 1-56. Treatment repeats every 56 days for 6 courses in the absence of disease progression or unacceptable toxicity. At the treating physician's discretion, patients may continue treatment past 6 courses if they are without disease progression.</description>
          </group>
        </group_list>
        <measure>
          <title>Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4)</title>
          <description>The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns within patient groups. In addition, we will review all adverse event data that is graded as 3, 4, or 5 and classified as either &quot;unrelated&quot; or &quot;unlikely to be related&quot; to study treatment in the event of an actual relationship developing. The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below.</description>
          <units>percentage of patients</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Platelet count decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="64.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White blood cell decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Neutrophil count decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypertension</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Premature menopause</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Patient-reported Symptoms Assessed Using the MPN-SAF, as Measured by the Percentage of Patients With a Decrease in MPN-SAF TSS Greater Than 50% From Baseline</title>
        <description>Patient-reported symptoms will be described at each time point using the mean, confidence interval, median, and range. The Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) will be analyzed using published scoring algorithms. MPN-SAF includes 27 items scored on a scale of 0 to 10. The MPN-SAF Total Symptom Score (TSS) (range 0-100) was computed according to the published scoring algorithm. Higher scores represent worse symptom burden. The percentage of patients with a decrease in MPN-SAF TSS greater than 50% from baseline and 95% confidence interval are reported below.</description>
        <time_frame>Baseline to up to 2 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Supportive Care (Ruxolitinib Phosphate and Danazol)</title>
            <description>Patients receive ruxolitinib phosphate PO 10 mg BID and danazol PO 200 mg TID on days 1-56. Treatment repeats every 56 days for 6 courses in the absence of disease progression or unacceptable toxicity. At the treating physician's discretion, patients may continue treatment past 6 courses if they are without disease progression.</description>
          </group>
        </group_list>
        <measure>
          <title>Patient-reported Symptoms Assessed Using the MPN-SAF, as Measured by the Percentage of Patients With a Decrease in MPN-SAF TSS Greater Than 50% From Baseline</title>
          <description>Patient-reported symptoms will be described at each time point using the mean, confidence interval, median, and range. The Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) will be analyzed using published scoring algorithms. MPN-SAF includes 27 items scored on a scale of 0 to 10. The MPN-SAF Total Symptom Score (TSS) (range 0-100) was computed according to the published scoring algorithm. Higher scores represent worse symptom burden. The percentage of patients with a decrease in MPN-SAF TSS greater than 50% from baseline and 95% confidence interval are reported below.</description>
          <units>percentage of patients</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28.6" lower_limit="8.4" upper_limit="58.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 2 years</time_frame>
      <desc>CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation and scientific analysis and is a single MedDRA Lowest Level Term (LLT).</desc>
      <group_list>
        <group group_id="E1">
          <title>Supportive Care (Ruxolitinib Phosphate and Danazol)</title>
          <description>Patients receive ruxolitinib phosphate PO 10 mg BID and danazol PO 200 mg TID on days 1-56. Treatment repeats every 56 days for 6 courses in the absence of disease progression or unacceptable toxicity. At the treating physician's discretion, patients may continue treatment past 6 courses if they are without disease progression.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 12</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="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>General disorders and administration site conditions - Other, specify</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Sudden death NOS</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Intracranial hemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Transient ischemic attacks</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 12</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="14" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="24" subjects_affected="9" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="6" subjects_affected="3" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="6" subjects_affected="3" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="29" subjects_affected="12" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" events="9" subjects_affected="5" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Irregular menstruation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Premature menopause</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Periorbital edema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Photosensitivity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE 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>Ruben A. Mesa, M.D.</name_or_title>
      <organization>Mayo Clinic</organization>
      <phone>480/301-8335</phone>
      <email>mesa.ruben@mayo.edu</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/NCT01732445
org study id: MC1283
secondary id: NCI-2012-02201
secondary id: MC1283
secondary id: P30CA015083
nct id: NCT01732445
lead sponsor: 
collaborator: 
has dmc: Yes
This phase II pilot trial studies how well ruxolitinib phosphate and danazol work in treating
      anemia in patients with myelofibrosis. Ruxolitinib phosphate and danazol may cause the body
      to make more red blood cells. They are used to treat anemia in patients with myelofibrosis.
PRIMARY OBJECTIVES:

      I. To evaluate the efficacy (best overall response) of ruxolitinib (ruxolitinib phosphate)
      and danazol in patients with myelofibrosis suffering from anemia.

      SECONDARY OBJECTIVES:

      I. To evaluate the overall survival of patients with myelofibrosis suffering from anemia
      initiating ruxolitinib and danazol.

      II. To evaluate the adverse event profile of ruxolitinib and danazol in patients with
      myelofibrosis suffering from anemia.

      TERTIARY OBJECTIVES:

      I. To evaluate quality of life (QOL) and patient-reported symptoms using the
      Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) and European Organization for
      Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) with
      ruxolitinib and danazol for patients with myelofibrosis suffering from anemia.

      OUTLINE:

      Patients receive ruxolitinib phosphate orally (PO) twice daily (BID) and danazol PO thrice
      daily (TID) on days 1-56. Treatment repeats every 56 days for 6 courses in the absence of
      disease progression or unacceptable toxicity. At the treating physician's discretion,
      patients may continue treatment past 6 courses if they are without disease progression.

      After completion of study treatment, patients are followed up every 6 months for 2 years.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Supportive Care
masking: None (Open Label)
measure: Best Overall Response Rate as Determined by International Working Group Criteria
time frame: Up to 2 years
description: Best overall response rate as determined by International Working Group criteria: An evaluable patient will be classified as a responder for the primary endpoint if the patient's best overall response is CR, PR or CI (Clinical Improvement) as determined by International Working Group Criteria over all cycles of study treatment. The percentage of successes will be estimated by the number of successes (defined as complete response, partial response, or clinical improvement) divided by the total number of evaluable patients times 100. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.
measure: Survival Time
time frame: From registration to death due to any cause, assessed up to 2 years
description: Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier. The median and 95% confidence interval are reported below.
measure: Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4)
time frame: Up to 2 years
description: The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns within patient groups. In addition, we will review all adverse event data that is graded as 3, 4, or 5 and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing. The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below.
measure: Patient-reported Symptoms Assessed Using the MPN-SAF, as Measured by the Percentage of Patients With a Decrease in MPN-SAF TSS Greater Than 50% From Baseline
time frame: Baseline to up to 2 years
description: Patient-reported symptoms will be described at each time point using the mean, confidence interval, median, and range. The Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) will be analyzed using published scoring algorithms. MPN-SAF includes 27 items scored on a scale of 0 to 10. The MPN-SAF Total Symptom Score (TSS) (range 0-100) was computed according to the published scoring algorithm. Higher scores represent worse symptom burden. The percentage of patients with a decrease in MPN-SAF TSS greater than 50% from baseline and 95% confidence interval are reported below.
arm group label: Supportive care (ruxolitinib phosphate and danazol)
arm group type: Experimental
description: Patients receive ruxolitinib phosphate PO BID and danazol PO TID on days 1-56. Treatment repeats every 56 days for 6 courses in the absence of disease progression or unacceptable toxicity. At the treating physician's discretion, patients may continue treatment past 6 courses if they are without disease progression.
intervention type: Drug
intervention name: ruxolitinib phosphate
description: Given PO
arm group label: Supportive care (ruxolitinib phosphate and danazol)
other name: INCB18424
other name: Jakafi
other name: oral JAK inhibitor INCB18424
other name: oral Janus-associated kinase inhibitor INCB18424
intervention type: Drug
intervention name: danazol
description: Given PO
arm group label: Supportive care (ruxolitinib phosphate and danazol)
other name: Chronogyn
other name: DAN
other name: Danocrine
intervention type: Other
intervention name: quality-of-life assessment
description: Ancillary studies
arm group label: Supportive care (ruxolitinib phosphate and danazol)
other name: quality of life assessment
intervention type: Other
intervention name: questionnaire administration
description: Ancillary studies
arm group label: Supportive care (ruxolitinib phosphate and danazol)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ruben Mesa
role: Principal Investigator
affiliation: Mayo Clinic
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Anemia
mesh term: Primary Myelofibrosis
mesh term: Danazol
mesh term: Janus Kinase Inhibitors
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 