<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/NCT01712659</url>
  </required_header>
  <id_info>
    <org_study_id>130006</org_study_id>
    <secondary_id>13-C-0006</secondary_id>
    <nct_id>NCT01712659</nct_id>
  </id_info>
  <brief_title>Ruxolitinib for Adult T-Cell Leukemia</brief_title>
  <official_title>Phase I/II Trial Evaluating the Safety and Efficacy of Ruxolitinib in Subjects With Smoldering and Chronic Adult T-cell Leukemia (ATL)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institutes of Health Clinical Center (CC)</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background:&#xD;
&#xD;
        -  The human T-cell leukemia virus 1 (HTLV-1) causes adult T-cell leukemia (ATL). Infection&#xD;
           does not immediately cause ATL, but it can develop over time. ATL is a rare and&#xD;
           aggressive type of cancer that disrupts the body's ability to control the HTLV-1 virus.&#xD;
           Infected T lymphocytes that are transformed by HTLV-1 into malignant ATL cell have&#xD;
           constitutively activated Interleukin-2 (IL-2), IL-9 and IL-15 production pathways that&#xD;
           function as autocrine and paracrine stimulators of these cells by stimulating these&#xD;
           cells through the Janus Kinase (JAK) 1 and 3/Signal transducer and activator of&#xD;
           transcription 5 (STAT5) pathways.&#xD;
&#xD;
        -  Ruxolitinib is a drug that has been approved to treat bone marrow disorders. Ruxolitinib&#xD;
           is a tyrosine kinase inhibitor that disrupts signaling through the JAK 1 and 2/STAT3 and&#xD;
           5 pathways and have potential as a treatment for ATL. Researchers want to see if&#xD;
           ruxolitinib can be a safe and effective treatment for ATL.&#xD;
&#xD;
        -  Initially this trial was designed as a single dose level phase II trial with ruxolitinib&#xD;
           given at the dose approved for the treatment of primary myelofibrosis, post-polycythemia&#xD;
           vera myelofibrosis and post-essential thrombocythemia myelofibrosis.&#xD;
&#xD;
        -  Clinical and correlative laboratory data demonstrated limited inhibition and impact on&#xD;
           the subject's disease with the standard 20 mg twice daily dose. Given that the&#xD;
           manufacturers of ruxolitinib had safety data for administering ruxolitinib to normal&#xD;
           healthy volunteers at doses up to 50 mg twice or 100 mg once daily, the trial was&#xD;
           reconfigured as a phase I dose escalation trial giving these higher doses on the twice&#xD;
           daily schedule&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
      Initial Phase II design:&#xD;
&#xD;
        -  Define clinical or objective response rate for the 20 mg twice daily dose of&#xD;
           Ruxolitinib.&#xD;
&#xD;
        -  Define safety profile, Time to progression and survival time.&#xD;
&#xD;
      Subsequent Phase I dose escalation with expansion cohort treated at the MTD or MAD:&#xD;
&#xD;
        -  Determine the maximum tolerated dose (MTD) and clinical response rate for ruxolitinib&#xD;
           administered at the higher dose levels.&#xD;
&#xD;
        -  Determine safety profile, time to progression&#xD;
&#xD;
        -  To test the safety and effectiveness of ruxolitinib for adult T-cell leukemia.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
      - Individuals at least 18 years of age who have ATL caused by HTLV-1.&#xD;
&#xD;
      Design:&#xD;
&#xD;
        -  Participants will be screened with a physical exam and medical history. Blood and urine&#xD;
           samples will be collected. Imaging studies will also be performed.&#xD;
&#xD;
        -  Participants will take ruxolitinib twice a day for 28 days. They will have blood tests&#xD;
           on days 1, 14, and 28. These tests will look at the levels of HTLV-1 in the blood.&#xD;
           Participants will have a final blood test about 2 weeks later. Treatment will also be&#xD;
           monitored with imaging studies.&#xD;
&#xD;
        -  Participants who have a partial response during treatment may be able to start taking&#xD;
           ruxolitinib again after the final blood test. They will continue to take ruxolitinib for&#xD;
           as long as it is effective and the side effects are not severe.&#xD;
&#xD;
        -  Participants who have a full response during treatment will take ruxolitinib for 56 more&#xD;
           days, and then stop treatment. If ATL returns, they may restart treatment and continue&#xD;
           it for as long as it is effective.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background:&#xD;
&#xD;
        -  Adult T-cell leukemia is a lymphoproliferative disorder characterized by the presence of&#xD;
           cluster of differentiation 4 (CD4)/cluster of differentiation 25 (CD25) expressing T&#xD;
           cells (interleukin-2 receptor (IL-2R) alpha expressing) in the peripheral blood, in&#xD;
           lymphoid and other tissues.&#xD;
&#xD;
        -  In smoldering and chronic adult T-cell leukemia (ATL) the human T-cell leukemia virus 1&#xD;
           (HTLV-1) encoded protein, Tax constitutively activates interleukin-2 (IL-2), IL-9 and&#xD;
           IL-15 autocrine/paracrine systems that in turn activate the Janus kinase&#xD;
           (JAK)-1/3/signal transducer and activator of transcription 5 (STAT5) pathways.&#xD;
&#xD;
        -  Ruxolitinib a therapeutic agent inhibits cytokine mediated Janus kinase (JAK)-1/2&#xD;
           activation and ex vivo proliferation of malignant T cells from subjects with ATL.&#xD;
&#xD;
        -  Ruxolitinib is a potent orally bioavailable JAK1/2 inhibitor not licensed for the&#xD;
           treatment of ATL.&#xD;
&#xD;
      Primary Objective:&#xD;
&#xD;
      Objective Initial Phase II:&#xD;
&#xD;
        -  To determine clinical or objective response rate for ruxolitinib given at 20 mg twice&#xD;
           daily&#xD;
&#xD;
        -  Primary Objective Dose Escalation Phase I: To determine the maximum tolerated dose and&#xD;
           clinical response rate for ruxolitinib given at doses of 30, 40 or 50 mg orally twice&#xD;
           daily in subjects with smoldering, chronic and biologically indolent acute or&#xD;
           lymphomatous subtype of ATL&#xD;
&#xD;
      Eligibility&#xD;
&#xD;
        -  Subjects greater than or equal to 18 years old with pathologically confirmed adult&#xD;
           T-cell leukemia: smoldering or chronic or previously treated lymphomatous or acute&#xD;
           subtypes with clinically indolent behavior indicated by lack of significant symptoms and&#xD;
           treatment free interval of greater than 6 months.&#xD;
&#xD;
        -  Subjects must have measurable or evaluable disease. Subjects with &gt; 10% of their PBMCs&#xD;
           having the characteristic abnormal (i.e., CD3dim, CD4 plus CD25 plus expressing)&#xD;
           fluorescence activated cell sorting (FACS) profile for circulating ATL cells will be&#xD;
           considered to have measurable disease.&#xD;
&#xD;
        -  Subjects with symptomatic leukemic meningitis, bony or gastrointestinal (GI) tract&#xD;
           involvement, serum calcium or Lactate dehydrogenase (LDH) &gt; 1.5 times the upper limit of&#xD;
           normal will be excluded. However, subjects that have both ATL and another HTLV-1&#xD;
           associated disease such as tropical spastic paraparesis (human T-cell leukemia virus 1&#xD;
           (HTLV-1) Associated Myelopathy (HAM)/tropical spastic paraparesis (TSP)) will be&#xD;
           included.&#xD;
&#xD;
        -  No prior treatment with another JAK inhibitor; subjects previously treated in this&#xD;
           protocol at the lower dose are eligible to restart treatment at the higher dose levels.&#xD;
&#xD;
      Design&#xD;
&#xD;
      - This is a pilot open-label, trial with off label-use of oral ruxolitinib that will treat 27&#xD;
      to 33 Subjects with smoldering or chronic or clinically indolent ATL. Groups of 3 to 6 newly&#xD;
      enrolled or reenrolled Subjects will begin treatment at an elevated dose of 30 mg orally&#xD;
      given twice daily. If this dose is tolerated without exceeding the criteria for dose limiting&#xD;
      toxicity (DLT) during the first cycle of treatment, the tolerability of treatment at 40 mg&#xD;
      and then 50 mg twice daily will be evaluated.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    The adult T-cell leukemia (ATL) research program was terminated after the death of the T-cell&#xD;
    malignancy group Lead investigator.&#xD;
  </why_stopped>
  <start_date type="Actual">October 26, 2012</start_date>
  <completion_date type="Actual">January 18, 2022</completion_date>
  <primary_completion_date type="Actual">November 12, 2021</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Phase II: Best Response</measure>
    <time_frame>From the time of the start of treatment to approximately 3 years of 5</time_frame>
    <description>Best response is complete response (CR) plus partial response (PR). Response was measured by the Revised Response Criteria for Lymphoma by Cheson, et al, and the International Consensus Meeting Criteria for Adult T-Cell Lymphoma (ATL). Complete response is disappearance of all clinical, microscopic, and radiographic evidence of disease. Partial response is a ≥50% reduction in the sum of the products of the greatest diameters of measurable disease without the appearance of new lesion. Stable disease is failure to attain complete response, partial response, or progressive disease. Progressive disease in peripheral blood is defined by a 50% increase from nadir in the count of flower cells and an absolute lymphocyte count, including flower cells, of 4x10^9/L; or the appearance of new lesions excluding skin.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase I: Maximum Tolerated Dose (MTD)</measure>
    <time_frame>From the time of the start of treatment to approximately 1 year</time_frame>
    <description>MTD is defined as the dose level at which no more than 1 of up to 6 participants experience dose-limiting toxicity (DLT) during the first cycle (28 days) treatment, and the dose below that at which at least 2 (of ≤6) participants have DLT as a result of the drug. A DLT is any grade 3 or 4 toxicity, if deemed possibly, probably, or definitely related to the study drug by the principal investigator during the first cycle of treatment with some exceptions such as Grade 3 anemia without hemolysis. Grade 3 or 4 granulocytopenia or leukopenia without infection, Grade 3 thrombocytopenia without bleeding, and Grade 3 or 4 lymphopenia. Grade 3 is severe or medically significant. Grade 4 is life-threatening, urgent intervention indicated.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Phase II: Time to Progression (TTP)</measure>
    <time_frame>From the time of the start of treatment to approximately 3 years</time_frame>
    <description>TTP is defined as the date of protocol consent until date of progressive disease is documented. Progressive disease was assessed by the Revised Response Criteria for Lymphoma by Cheson, et al, and the International Consensus Meeting Criteria for Adult T-Cell Lymphoma (guideline (version 1.1). Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, and the appearance of one or more new lesions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase II: Survival Time</measure>
    <time_frame>From the time of the start of treatment to approximately 3 years</time_frame>
    <description>Survival time is defined as the date of protocol consent until the date of the subject's death for any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase I: Grade of Serious and/or Non-serious Adverse Events (SAEs) Related to the Experimental Treatment by Grade</measure>
    <time_frame>From the time of the start of treatment to approximately 1 year</time_frame>
    <description>Grade of serious adverse events (SAEs) related to the experimental treatment. Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, and Grade 4 is life-threatening.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase I: Time to Progression When Ruxolitinib is Administered at Doses of 30, 40 or 50 mg Orally Twice Daily</measure>
    <time_frame>From the time of the start of treatment to approximately 1 year</time_frame>
    <description>TTP is defined as the date of protocol consent until date of progressive disease is documented. Progressive disease was assessed by the Revised Response Criteria for Lymphoma by Cheson, et al, and the International Consensus Meeting Criteria for Adult T-Cell Lymphoma guidelines (version 1.1). Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, and the appearance of one or more new lesions.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Number of Participants With a Dose Limiting Toxicity (DLT)</measure>
    <time_frame>During the first cycle of treatment (28 days)</time_frame>
    <description>A DLT is any grade 3 or 4 toxicity, if deemed possibly, probably or definitely related to the study drug by the principal investigator during the first cycle of treatment with some exceptions such as Grade 3 anemia without hemolysis. Grade 3 or 4 granulocytopenia or leukopenia without infection, Grade 3 thrombocytopenia without bleeding, and Grade 3 or 4 lymphopenia. Grade 3 is severe or medically significant. Grade 4 is life-threatening, urgent intervention indicated.</description>
  </other_outcome>
  <other_outcome>
    <measure>Number of Participants With Non-Serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0).</measure>
    <time_frame>Date treatment consent signed to date off study, approximately 110 months and 27 days.</time_frame>
    <description>Here is the number of participants with non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence.</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">19</enrollment>
  <condition>T Cell Leukemia, Adult</condition>
  <condition>Leukemia, Adult T-Cell</condition>
  <condition>T Cell Leukemia, HTLV I Associated</condition>
  <arm_group>
    <arm_group_label>Original Phase II Standard Ruxolitinib dose cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ruxolitinib 20 mg orally twice daily for 28 days. Subjects may continue to receive treatment until progressive disease (PD) or unacceptable toxicity.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>2- Phase 1 Dose Escalation cohorts</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.&#xD;
Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.&#xD;
Dose level 3: Ruxolitinib: Ruxolitinib 50 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>3- Phase 1 Dose Expansion Cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ruxolitinib at the maximum tolerated dose (MTD) or the maximum administered dose (MAD) defined in the phase 1 dose escalation cohorts. Subjects may continue to receive treatment until progressive disease (PD) or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ruxolitinib</intervention_name>
    <description>Ruxolitinib 20 mg orally twice daily for 28 days. Subjects may continue to receive treatment until progressive disease (PD) or unacceptable toxicity.</description>
    <arm_group_label>3- Phase 1 Dose Expansion Cohort</arm_group_label>
    <arm_group_label>Original Phase II Standard Ruxolitinib dose cohort</arm_group_label>
    <other_name>Jakafi</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ruxolitinib</intervention_name>
    <description>Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.</description>
    <arm_group_label>2- Phase 1 Dose Escalation cohorts</arm_group_label>
    <other_name>Jakafi</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ruxolitinib</intervention_name>
    <description>Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.</description>
    <arm_group_label>2- Phase 1 Dose Escalation cohorts</arm_group_label>
    <other_name>Jakafi</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ruxolitinib</intervention_name>
    <description>Ruxolitinib 50 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.</description>
    <arm_group_label>2- Phase 1 Dose Escalation cohorts</arm_group_label>
    <other_name>Jakafi</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA:&#xD;
&#xD;
        NOTE: After approval and activation of Amendment D, subjects who have failed this protocol&#xD;
        treatment previously at the initial dose level may be eligible for re-enrollment and&#xD;
        retreatment if they otherwise meet eligibility criteria.&#xD;
&#xD;
          -  Subjects greater than or equal to 18 years old with pathologically confirmed adult T-&#xD;
             cell leukemia: smoldering or chronic, or previously treated lymphomatous or acute&#xD;
             subtypes with clinically indolent behavior indicated by lack of significant symptoms&#xD;
             and treatment free interval of greater than 6 months are eligible for treatment in the&#xD;
             dose escalation and expansion cohorts.&#xD;
&#xD;
          -  Subjects must have serum antibodies directed to human T-cell lymphotropic virus type 1&#xD;
             (HTLV-1).&#xD;
&#xD;
          -  Subjects must have measurable or evaluable disease. Subjects with &gt; 10% of the&#xD;
             peripheral blood mononuclear cells (PBMCs) having the characteristic abnormal (i.e.,&#xD;
             CD3dim, cluster of differentiation 4 (CD4) plus cluster of differentiation 25 (CD25)&#xD;
             plus expressing) fluorescence-activated cell sorting (FACS) profile for circulating&#xD;
             adult T-cell leukemia (ATL) cells will be considered to have evaluable disease.&#xD;
&#xD;
          -  Subjects must have adequate physiologic parameters:&#xD;
&#xD;
          -  Absolute granulocyte count greater than or equal to 500 K/microL, platelet count&#xD;
             greater than or equal to 75,000 K/microL and hemoglobin greater than or equal to 10&#xD;
             g/dL.&#xD;
&#xD;
          -  Bilirubin and creatinine less than or equal to 1.5 times institutional upper limit of&#xD;
             normal (ULN).&#xD;
&#xD;
          -  Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) less than or equal to&#xD;
             3.0 times institutional ULN.&#xD;
&#xD;
          -  Karnofsky Performance Score greater than or equal to 70% or Eastern Cooperative&#xD;
             Oncology Group (ECOG) less than or equal 1.&#xD;
&#xD;
          -  Subjects must be able to understand and sign Informed Consent Form.&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
          -  Subjects with symptomatic leukemic meningitis, bony or gastrointestinal (GI) tract&#xD;
             involvement, serum calcium or lactate dehydrogenase (LDH) &gt; 1.5 times the upper limit&#xD;
             of normal will be excluded. However, subjects that have both ATL and another HTLV-1&#xD;
             associated disease such as tropical spastic paraparesis (human T-cell lymphotropic&#xD;
             virus type 1 (HTLV-1) Associated Myelopathy (HAM)/tropical spastic paraparesis (TSP)&#xD;
             will be included.&#xD;
&#xD;
          -  Subjects with symptomatic leukemic meningitis, bony or GI tract involvement, serum&#xD;
             calcium or LDH &gt; 1.5 X the upper limit of normal will be excluded. However, subjects&#xD;
             that have both ATL and another HTLV-1 associated disease such as tropical spastic&#xD;
             paraparesis (HAM/TSP) will be included.&#xD;
&#xD;
          -  Subjects who have received high doses of systemic corticosteroids for the treatment of&#xD;
             their ATL within 4 weeks prior to the start of therapy.&#xD;
&#xD;
          -  Subjects who have received any cytotoxic therapy, immunotherapy, antitumor vaccines or&#xD;
             monoclonal antibodies in the 4 weeks prior to the start of the study.&#xD;
&#xD;
          -  Life expectancy of less than 3 months.&#xD;
&#xD;
          -  Documented active bacterial infections, HTLV-II infection, or hepatitis B or C as&#xD;
             follows:&#xD;
&#xD;
               -  A positive hepatitis B serology indicative of previous immunization (i.e.,&#xD;
                  hepatitis B surface antigen (HBsAb) positive and hepatitis B core antibody&#xD;
                  (HBcAb) negative), or a fully resolved acute hepatitis B infection is not an&#xD;
                  exclusion criterion.&#xD;
&#xD;
               -  Subjects with an indolent chronic hepatitis B infection (normal ALT, AST, albumin&#xD;
                  and no radiographic or biopsy evidence of cirrhosis) may be eligible.&#xD;
&#xD;
               -  Subjects with active hepatitis C are excluded. Subjects positive for hepatitis C&#xD;
                  virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is&#xD;
                  negative for HCV ribonucleic acid (RNA).&#xD;
&#xD;
          -  Subjects who have untreated human immunodeficiency virus (HIV) are not eligible for&#xD;
             this study because by definition they have a defective immune response and are at much&#xD;
             higher risk for opportunistic infections due to immune disregulation by both HTLV-1&#xD;
             and HTLVIII (HIV) viruses. Subjects on HIV therapy with undetectable viral loads as&#xD;
             measured by HIV RNA quantitative real time PCR may be eligible.&#xD;
&#xD;
          -  Inability or refusal to practice effective contraception during therapy. Men and women&#xD;
             of childbearing potential must use an effective method of birth control or abstinence&#xD;
             during treatment and for 1 week after completion of the treatment.&#xD;
&#xD;
          -  Subject has significant and/or uncontrolled cardiac, renal, hepatic or other systemic&#xD;
             disorders or significant psychological conditions at baseline visit that in the&#xD;
             investigators judgment would jeopardize subject enrollment or compliance with the&#xD;
             study procedures.&#xD;
&#xD;
          -  Subjects with an absolute requirement for a medication that is a strong inhibitor of&#xD;
             Cytochrome P450 3A4 (P450 CYP3A4) are not eligible.&#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>Kevin C Conlon, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Cancer Institute (NCI)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Institutes of Health Clinical Center, 9000 Rockville Pike</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2013-C-0006.html</url>
    <description>NIH Clinical Center Detailed Web Page</description>
  </link>
  <reference>
    <citation>Matsuoka M, Jeang KT. Human T-cell leukemia virus type 1 (HTLV-1) and leukemic transformation: viral infectivity, Tax, HBZ and therapy. Oncogene. 2011 Mar 24;30(12):1379-89. doi: 10.1038/onc.2010.537. Epub 2010 Nov 29.</citation>
    <PMID>21119600</PMID>
  </reference>
  <reference>
    <citation>Tsukasaki K, Hermine O, Bazarbachi A, Ratner L, Ramos JC, Harrington W Jr, O'Mahony D, Janik JE, Bittencourt AL, Taylor GP, Yamaguchi K, Utsunomiya A, Tobinai K, Watanabe T. Definition, prognostic factors, treatment, and response criteria of adult T-cell leukemia-lymphoma: a proposal from an international consensus meeting. J Clin Oncol. 2009 Jan 20;27(3):453-9. doi: 10.1200/JCO.2008.18.2428. Epub 2008 Dec 8.</citation>
    <PMID>19064971</PMID>
  </reference>
  <reference>
    <citation>Yamada Y, Atogami S, Hasegawa H, Kamihira S, Soda M, Satake M, Yamaguchi K. [Nationwide survey of adult T-cell leukemia/lymphoma (ATL) in Japan]. Rinsho Ketsueki. 2011 Nov;52(11):1765-71. Japanese.</citation>
    <PMID>22185799</PMID>
  </reference>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>October 20, 2012</study_first_submitted>
  <study_first_submitted_qc>October 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 23, 2012</study_first_posted>
  <results_first_submitted>November 10, 2022</results_first_submitted>
  <results_first_submitted_qc>December 15, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">January 10, 2023</results_first_posted>
  <last_update_submitted>December 15, 2022</last_update_submitted>
  <last_update_submitted_qc>December 15, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 10, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>National Cancer Institute (NCI)</investigator_affiliation>
    <investigator_full_name>Kevin Conlon, MD</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>JAK 1/2</keyword>
  <keyword>Human T-Cell Lymphotropic Virus 1</keyword>
  <keyword>HTLV-1</keyword>
  <keyword>Janus Kinase Inhibitor</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Leukemia, T-Cell</mesh_term>
    <mesh_term>Leukemia-Lymphoma, Adult T-Cell</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request.&#xD;
All collected IPD will be shared with collaborators under the terms of collaborative agreements.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>Clinical data available during the study and indefinitely.</ipd_time_frame>
    <ipd_access_criteria>Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI).</ipd_access_criteria>
  </patient_data>
  <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>February 10, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/59/NCT01712659/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>January 11, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/59/NCT01712659/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>No participants were enrolled on dose level 3 or the expansion cohort for the phase I dose escalation version of the protocol because the adult T-cell leukemia (ATL) research program was terminated after the death of the T-cell malignancy group Lead investigator.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Original Phase II Standard Ruxolitinib Dose Cohort - 20 mg Twice Daily</title>
          <description>Ruxolitinib 20 mg orally twice daily for 28 days. Subject may continue to receive treatment until progressive disease (PD) or unacceptable toxicity.</description>
        </group>
        <group group_id="P2">
          <title>2- Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily</title>
          <description>Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.</description>
        </group>
        <group group_id="P3">
          <title>2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily</title>
          <description>Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.</description>
        </group>
        <group group_id="P4">
          <title>2- Phase 1 Dose Escalation Cohorts Dose Level 3 - 50 mg Twice Daily</title>
          <description>Dose level 3: Ruxolitinib: Ruxolitinib 50 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.</description>
        </group>
        <group group_id="P5">
          <title>3- Phase 1 Dose Expansion Cohort</title>
          <description>Ruxolitinib at the maximum tolerated dose (MTD) or the maximum administered dose (MAD) defined in the phase 1 dose escalation cohorts. Subjects may continue to receive treatment until progressive disease (PD) or unacceptable toxicity.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Dose Escalation</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Unable to take study drug</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Dose Expansion</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Early disease progression</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Participants Re-Enrolled and Treated</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1">Participant treated in the original 20 mg group was re-enrolled and treated at 30 mg twice daily (the protocol allowed this)</participants>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Original Phase II Standard Ruxolitinib Dose Cohort - 20 mg Twice Daily</title>
          <description>Ruxolitinib 20 mg orally twice daily for 28 days. Subject may continue to receive treatment until progressive disease (PD) or unacceptable toxicity.</description>
        </group>
        <group group_id="B2">
          <title>2- Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily</title>
          <description>Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.</description>
        </group>
        <group group_id="B3">
          <title>2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily</title>
          <description>Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="12"/>
            <count group_id="B2" value="6"/>
            <count group_id="B3" value="1"/>
            <count group_id="B4" value="19"/>
          </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 group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="17"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="44.5" spread="14.5"/>
                    <measurement group_id="B2" value="46.3" spread="10.9"/>
                    <measurement group_id="B3" value="65" spread="0"/>
                    <measurement group_id="B4" value="51.93" spread="12.7"/>
                  </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 group_id="B2" value="3"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </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 group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </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="12"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Adult T-Cell Leukemia Lymphoma Diagnosis</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Performance Status</title>
          <description>Performance status 0 is Normal activity. Fully active, able to carry on all pre-disease performance without restriction. Performance status 1 is symptoms, but ambulatory.&#xD;
Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature (e.g., light housework, office work).</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Prior Therapy</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Surgery</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Chemotherapy</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Radiation Therapy</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Molecular</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Immunotherapy</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Treatment Naive</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Phase II: Best Response</title>
        <description>Best response is complete response (CR) plus partial response (PR). Response was measured by the Revised Response Criteria for Lymphoma by Cheson, et al, and the International Consensus Meeting Criteria for Adult T-Cell Lymphoma (ATL). Complete response is disappearance of all clinical, microscopic, and radiographic evidence of disease. Partial response is a ≥50% reduction in the sum of the products of the greatest diameters of measurable disease without the appearance of new lesion. Stable disease is failure to attain complete response, partial response, or progressive disease. Progressive disease in peripheral blood is defined by a 50% increase from nadir in the count of flower cells and an absolute lymphocyte count, including flower cells, of 4x10^9/L; or the appearance of new lesions excluding skin.</description>
        <time_frame>From the time of the start of treatment to approximately 3 years of 5</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Original Phase II Standard Ruxolitinib Dose Cohort - 20 mg Twice Daily</title>
            <description>Ruxolitinib 20 mg orally twice daily for 28 days. Subject may continue to receive treatment until progressive disease (PD) or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>2- Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily</title>
            <description>Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.</description>
          </group>
          <group group_id="O3">
            <title>2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily</title>
            <description>Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase II: Best Response</title>
          <description>Best response is complete response (CR) plus partial response (PR). Response was measured by the Revised Response Criteria for Lymphoma by Cheson, et al, and the International Consensus Meeting Criteria for Adult T-Cell Lymphoma (ATL). Complete response is disappearance of all clinical, microscopic, and radiographic evidence of disease. Partial response is a ≥50% reduction in the sum of the products of the greatest diameters of measurable disease without the appearance of new lesion. Stable disease is failure to attain complete response, partial response, or progressive disease. Progressive disease in peripheral blood is defined by a 50% increase from nadir in the count of flower cells and an absolute lymphocyte count, including flower cells, of 4x10^9/L; or the appearance of new lesions excluding skin.</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="12"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Complete Response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Partial Response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Stable Disease</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Progressive Disease</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not Assessable</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Phase I: Maximum Tolerated Dose (MTD)</title>
        <description>MTD is defined as the dose level at which no more than 1 of up to 6 participants experience dose-limiting toxicity (DLT) during the first cycle (28 days) treatment, and the dose below that at which at least 2 (of ≤6) participants have DLT as a result of the drug. A DLT is any grade 3 or 4 toxicity, if deemed possibly, probably, or definitely related to the study drug by the principal investigator during the first cycle of treatment with some exceptions such as Grade 3 anemia without hemolysis. Grade 3 or 4 granulocytopenia or leukopenia without infection, Grade 3 thrombocytopenia without bleeding, and Grade 3 or 4 lymphopenia. Grade 3 is severe or medically significant. Grade 4 is life-threatening, urgent intervention indicated.</description>
        <time_frame>From the time of the start of treatment to approximately 1 year</time_frame>
        <population>No participants were treated in an expansion cohort (50mg) before the protocol was closed.</population>
        <group_list>
          <group group_id="O1">
            <title>2- Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily</title>
            <description>Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily</title>
            <description>Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.</description>
          </group>
          <group group_id="O3">
            <title>2- Phase 1 Dose Escalation Cohorts Dose Level 3 - 50 mg Twice Daily</title>
            <description>Dose level 3: Ruxolitinib: Ruxolitinib 50 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase I: Maximum Tolerated Dose (MTD)</title>
          <description>MTD is defined as the dose level at which no more than 1 of up to 6 participants experience dose-limiting toxicity (DLT) during the first cycle (28 days) treatment, and the dose below that at which at least 2 (of ≤6) participants have DLT as a result of the drug. A DLT is any grade 3 or 4 toxicity, if deemed possibly, probably, or definitely related to the study drug by the principal investigator during the first cycle of treatment with some exceptions such as Grade 3 anemia without hemolysis. Grade 3 or 4 granulocytopenia or leukopenia without infection, Grade 3 thrombocytopenia without bleeding, and Grade 3 or 4 lymphopenia. Grade 3 is severe or medically significant. Grade 4 is life-threatening, urgent intervention indicated.</description>
          <population>No participants were treated in an expansion cohort (50mg) before the protocol was closed.</population>
          <units>mg</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="1"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA">MTD was not defined because the Adult T-Cell Leukemia (ATL) project was terminated.</measurement>
                    <measurement group_id="O2" value="NA">MTD was not defined because the Adult T-Cell Leukemia (ATL) project was terminated.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase II: Time to Progression (TTP)</title>
        <description>TTP is defined as the date of protocol consent until date of progressive disease is documented. Progressive disease was assessed by the Revised Response Criteria for Lymphoma by Cheson, et al, and the International Consensus Meeting Criteria for Adult T-Cell Lymphoma (guideline (version 1.1). Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, and the appearance of one or more new lesions.</description>
        <time_frame>From the time of the start of treatment to approximately 3 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Original Phase II Standard Ruxolitinib Dose Cohort - 20 mg Twice Daily</title>
            <description>Ruxolitinib 20 mg orally twice daily for 28 days. Subject may continue to receive treatment until progressive disease (PD) or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>2- Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily</title>
            <description>Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.</description>
          </group>
          <group group_id="O3">
            <title>2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily</title>
            <description>Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase II: Time to Progression (TTP)</title>
          <description>TTP is defined as the date of protocol consent until date of progressive disease is documented. Progressive disease was assessed by the Revised Response Criteria for Lymphoma by Cheson, et al, and the International Consensus Meeting Criteria for Adult T-Cell Lymphoma (guideline (version 1.1). Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, and the appearance of one or more new lesions.</description>
          <units>Months</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="5"/>
                <count group_id="O3" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.25" spread="7.62"/>
                    <measurement group_id="O2" value="3.36" spread="3.34"/>
                    <measurement group_id="O3" value="1" spread="NA">Standard deviation is NA because it is only one participant.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase II: Survival Time</title>
        <description>Survival time is defined as the date of protocol consent until the date of the subject's death for any cause.</description>
        <time_frame>From the time of the start of treatment to approximately 3 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Original Phase II Standard Ruxolitinib Dose Cohort - 20 mg Twice Daily</title>
            <description>Ruxolitinib 20 mg orally twice daily for 28 days. Subject may continue to receive treatment until progressive disease (PD) or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>2- Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily</title>
            <description>Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.</description>
          </group>
          <group group_id="O3">
            <title>2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily</title>
            <description>Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase II: Survival Time</title>
          <description>Survival time is defined as the date of protocol consent until the date of the subject's death for any cause.</description>
          <units>Months</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.3" lower_limit="15.7" upper_limit="42.9"/>
                    <measurement group_id="O2" value="20.1" lower_limit="3.9" upper_limit="36.3"/>
                    <measurement group_id="O3" value="14.1" lower_limit="NA" upper_limit="NA">95% confidence interval cannot be calculated for one participant.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase I: Grade of Serious and/or Non-serious Adverse Events (SAEs) Related to the Experimental Treatment by Grade</title>
        <description>Grade of serious adverse events (SAEs) related to the experimental treatment. Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, and Grade 4 is life-threatening.</description>
        <time_frame>From the time of the start of treatment to approximately 1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Grade 1 - Original Phase II Standard Ruxolitinib Dose Cohort - 20 mg Twice Daily</title>
            <description>Ruxolitinib 20 mg orally twice daily for 28 days. Subject may continue to receive treatment until progressive disease (PD) or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>Grade 2 - Original Phase II Standard Ruxolitinib Dose Cohort - 20 mg Twice Daily</title>
            <description>Ruxolitinib 20 mg orally twice daily for 28 days. Subject may continue to receive treatment until progressive disease (PD) or unacceptable toxicity.</description>
          </group>
          <group group_id="O3">
            <title>Grade 3 - Original Phase II Standard Ruxolitinib Dose Cohort - 20 mg Twice Daily</title>
            <description>Ruxolitinib 20 mg orally twice daily for 28 days. Subject may continue to receive treatment until progressive disease (PD) or unacceptable toxicity.</description>
          </group>
          <group group_id="O4">
            <title>Grade 4 - Original Phase II Standard Ruxolitinib Dose Cohort - 20 mg Twice Daily</title>
            <description>Ruxolitinib 20 mg orally twice daily for 28 days. Subject may continue to receive treatment until progressive disease (PD) or unacceptable toxicity.</description>
          </group>
          <group group_id="O5">
            <title>Grade 1 - 2- Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily</title>
            <description>Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.</description>
          </group>
          <group group_id="O6">
            <title>Grade 2 - Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily</title>
            <description>Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.</description>
          </group>
          <group group_id="O7">
            <title>Grade 3 - Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily</title>
            <description>Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.</description>
          </group>
          <group group_id="O8">
            <title>Grade 4 - Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily</title>
            <description>Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.</description>
          </group>
          <group group_id="O9">
            <title>Grade 1 - 2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily</title>
            <description>Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.</description>
          </group>
          <group group_id="O10">
            <title>Grade 2 - 2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily</title>
            <description>Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.</description>
          </group>
          <group group_id="O11">
            <title>Grade 3 - 2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily</title>
            <description>Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.</description>
          </group>
          <group group_id="O12">
            <title>Grade 4 - 2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily</title>
            <description>Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase I: Grade of Serious and/or Non-serious Adverse Events (SAEs) Related to the Experimental Treatment by Grade</title>
          <description>Grade of serious adverse events (SAEs) related to the experimental treatment. Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, and Grade 4 is life-threatening.</description>
          <units>Adverse Events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="12"/>
                <count group_id="O3" value="12"/>
                <count group_id="O4" value="12"/>
                <count group_id="O5" value="6"/>
                <count group_id="O6" value="6"/>
                <count group_id="O7" value="6"/>
                <count group_id="O8" value="6"/>
                <count group_id="O9" value="1"/>
                <count group_id="O10" value="1"/>
                <count group_id="O11" value="1"/>
                <count group_id="O12" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Fatigue</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="1"/>
                    <measurement group_id="O6" value="0"/>
                    <measurement group_id="O7" value="0"/>
                    <measurement group_id="O8" value="0"/>
                    <measurement group_id="O9" value="0"/>
                    <measurement group_id="O10" value="0"/>
                    <measurement group_id="O11" value="0"/>
                    <measurement group_id="O12" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nausea</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                    <measurement group_id="O7" value="0"/>
                    <measurement group_id="O8" value="0"/>
                    <measurement group_id="O9" value="0"/>
                    <measurement group_id="O10" value="0"/>
                    <measurement group_id="O11" value="0"/>
                    <measurement group_id="O12" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="1"/>
                    <measurement group_id="O7" value="0"/>
                    <measurement group_id="O8" value="0"/>
                    <measurement group_id="O9" value="0"/>
                    <measurement group_id="O10" value="0"/>
                    <measurement group_id="O11" value="0"/>
                    <measurement group_id="O12" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Alanine aminotransferase increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="1"/>
                    <measurement group_id="O6" value="0"/>
                    <measurement group_id="O7" value="0"/>
                    <measurement group_id="O8" value="0"/>
                    <measurement group_id="O9" value="0"/>
                    <measurement group_id="O10" value="0"/>
                    <measurement group_id="O11" value="0"/>
                    <measurement group_id="O12" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Aspartate aminotransferase increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="1"/>
                    <measurement group_id="O6" value="0"/>
                    <measurement group_id="O7" value="0"/>
                    <measurement group_id="O8" value="0"/>
                    <measurement group_id="O9" value="0"/>
                    <measurement group_id="O10" value="0"/>
                    <measurement group_id="O11" value="0"/>
                    <measurement group_id="O12" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lymphocyte count decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="1"/>
                    <measurement group_id="O6" value="0"/>
                    <measurement group_id="O7" value="0"/>
                    <measurement group_id="O8" value="0"/>
                    <measurement group_id="O9" value="0"/>
                    <measurement group_id="O10" value="0"/>
                    <measurement group_id="O11" value="0"/>
                    <measurement group_id="O12" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Bilirubin increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                    <measurement group_id="O7" value="0"/>
                    <measurement group_id="O8" value="0"/>
                    <measurement group_id="O9" value="0"/>
                    <measurement group_id="O10" value="0"/>
                    <measurement group_id="O11" value="0"/>
                    <measurement group_id="O12" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White blood cells decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="1"/>
                    <measurement group_id="O6" value="0"/>
                    <measurement group_id="O7" value="0"/>
                    <measurement group_id="O8" value="0"/>
                    <measurement group_id="O9" value="1"/>
                    <measurement group_id="O10" value="0"/>
                    <measurement group_id="O11" value="0"/>
                    <measurement group_id="O12" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Platelet count decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                    <measurement group_id="O7" value="0"/>
                    <measurement group_id="O8" value="0"/>
                    <measurement group_id="O9" value="1"/>
                    <measurement group_id="O10" value="0"/>
                    <measurement group_id="O11" value="0"/>
                    <measurement group_id="O12" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Creatinine increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="2"/>
                    <measurement group_id="O6" value="0"/>
                    <measurement group_id="O7" value="0"/>
                    <measurement group_id="O8" value="0"/>
                    <measurement group_id="O9" value="0"/>
                    <measurement group_id="O10" value="0"/>
                    <measurement group_id="O11" value="0"/>
                    <measurement group_id="O12" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypernatremia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="1"/>
                    <measurement group_id="O7" value="0"/>
                    <measurement group_id="O8" value="0"/>
                    <measurement group_id="O9" value="0"/>
                    <measurement group_id="O10" value="0"/>
                    <measurement group_id="O11" value="0"/>
                    <measurement group_id="O12" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Alkaline phosphatase increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="1"/>
                    <measurement group_id="O6" value="0"/>
                    <measurement group_id="O7" value="0"/>
                    <measurement group_id="O8" value="0"/>
                    <measurement group_id="O9" value="0"/>
                    <measurement group_id="O10" value="0"/>
                    <measurement group_id="O11" value="0"/>
                    <measurement group_id="O12" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Neutrophil count decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                    <measurement group_id="O7" value="1"/>
                    <measurement group_id="O8" value="0"/>
                    <measurement group_id="O9" value="0"/>
                    <measurement group_id="O10" value="1"/>
                    <measurement group_id="O11" value="0"/>
                    <measurement group_id="O12" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase I: Time to Progression When Ruxolitinib is Administered at Doses of 30, 40 or 50 mg Orally Twice Daily</title>
        <description>TTP is defined as the date of protocol consent until date of progressive disease is documented. Progressive disease was assessed by the Revised Response Criteria for Lymphoma by Cheson, et al, and the International Consensus Meeting Criteria for Adult T-Cell Lymphoma guidelines (version 1.1). Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, and the appearance of one or more new lesions.</description>
        <time_frame>From the time of the start of treatment to approximately 1 year</time_frame>
        <population>No participants were enrolled on the expansion cohort for the phase I dose escalation (50mg) version of the protocol.</population>
        <group_list>
          <group group_id="O1">
            <title>Original Phase II Standard Ruxolitinib Dose Cohort - 20 mg Twice Daily</title>
            <description>Ruxolitinib 20 mg orally twice daily for 28 days. Subject may continue to receive treatment until progressive disease (PD) or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>2- Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily</title>
            <description>Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.</description>
          </group>
          <group group_id="O3">
            <title>2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily</title>
            <description>Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.</description>
          </group>
          <group group_id="O4">
            <title>2- Phase 1 Dose Escalation Cohorts Dose Level 3 - 50 mg Twice Daily</title>
            <description>Dose level 3: Ruxolitinib: Ruxolitinib 50 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase I: Time to Progression When Ruxolitinib is Administered at Doses of 30, 40 or 50 mg Orally Twice Daily</title>
          <description>TTP is defined as the date of protocol consent until date of progressive disease is documented. Progressive disease was assessed by the Revised Response Criteria for Lymphoma by Cheson, et al, and the International Consensus Meeting Criteria for Adult T-Cell Lymphoma guidelines (version 1.1). Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, and the appearance of one or more new lesions.</description>
          <population>No participants were enrolled on the expansion cohort for the phase I dose escalation (50mg) version of the protocol.</population>
          <units>Months</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="1"/>
                <count group_id="O4" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.2" lower_limit="0.89" upper_limit="9.51"/>
                    <measurement group_id="O2" value="4.1" lower_limit="0.77" upper_limit="7.43"/>
                    <measurement group_id="O3" value="1" lower_limit="NA" upper_limit="NA">95% confidence interval cannot be calculated for one participant.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Number of Participants With a Dose Limiting Toxicity (DLT)</title>
        <description>A DLT is any grade 3 or 4 toxicity, if deemed possibly, probably or definitely related to the study drug by the principal investigator during the first cycle of treatment with some exceptions such as Grade 3 anemia without hemolysis. Grade 3 or 4 granulocytopenia or leukopenia without infection, Grade 3 thrombocytopenia without bleeding, and Grade 3 or 4 lymphopenia. Grade 3 is severe or medically significant. Grade 4 is life-threatening, urgent intervention indicated.</description>
        <time_frame>During the first cycle of treatment (28 days)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Original Phase II Standard Ruxolitinib Dose Cohort - 20 mg Twice Daily</title>
            <description>Ruxolitinib 20 mg orally twice daily for 28 days. Subject may continue to receive treatment until progressive disease (PD) or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>2- Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily</title>
            <description>Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.</description>
          </group>
          <group group_id="O3">
            <title>2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily</title>
            <description>Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With a Dose Limiting Toxicity (DLT)</title>
          <description>A DLT is any grade 3 or 4 toxicity, if deemed possibly, probably or definitely related to the study drug by the principal investigator during the first cycle of treatment with some exceptions such as Grade 3 anemia without hemolysis. Grade 3 or 4 granulocytopenia or leukopenia without infection, Grade 3 thrombocytopenia without bleeding, and Grade 3 or 4 lymphopenia. Grade 3 is severe or medically significant. Grade 4 is life-threatening, urgent intervention indicated.</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="12"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Number of Participants With Non-Serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0).</title>
        <description>Here is the number of participants with non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence.</description>
        <time_frame>Date treatment consent signed to date off study, approximately 110 months and 27 days.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Original Phase II Standard Ruxolitinib Dose Cohort - 20 mg Twice Daily</title>
            <description>Ruxolitinib 20 mg orally twice daily for 28 days. Subject may continue to receive treatment until progressive disease (PD) or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>2- Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily</title>
            <description>Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.</description>
          </group>
          <group group_id="O3">
            <title>2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily</title>
            <description>Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Non-Serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0).</title>
          <description>Here is the number of participants with non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence.</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="12"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                    <measurement group_id="O2" value="6"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Date treatment consent signed to date off study, approximately 110 months and 27 days.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Original Phase II Standard Ruxolitinib Dose Cohort - 20 mg Twice Daily</title>
          <description>Ruxolitinib 20 mg orally twice daily for 28 days. Subject may continue to receive treatment until progressive disease (PD) or unacceptable toxicity.</description>
        </group>
        <group group_id="E2">
          <title>2- Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily</title>
          <description>Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.</description>
        </group>
        <group group_id="E3">
          <title>2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily</title>
          <description>Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</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="12" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="1"/>
              </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="7" subjects_affected="3" subjects_at_risk="12"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Eye pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </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="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Infusion site extravasation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infections and infestations - Other, Chikungunya virus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Infections and infestations - Other, Haemophilus influenzae bacteremia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Infections and infestations - Other, Shingles</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Activated partial thromboplastin time prolonged</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="12"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="12"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Investigations - Other, Blood lactate dehydrogenase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" events="10" subjects_affected="7" subjects_at_risk="12"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Lymphocyte count increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="9" subjects_affected="6" subjects_at_risk="12"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E3" events="6" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Serum amylase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="3" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hypernatremia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </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="12"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Paresthesia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Hoarseness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other, callous buildup on toes (unsure if related to ATL)</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Skin hyperpigmentation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </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>Kevin C. Conlon</name_or_title>
      <organization>National Cancer Institute</organization>
      <phone>240-858-3570</phone>
      <email>conlonkc@mail.nih.gov</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/NCT01712659
org study id: 130006
secondary id: 13-C-0006
nct id: NCT01712659
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Background:

        -  The human T-cell leukemia virus 1 (HTLV-1) causes adult T-cell leukemia (ATL). Infection
           does not immediately cause ATL, but it can develop over time. ATL is a rare and
           aggressive type of cancer that disrupts the body's ability to control the HTLV-1 virus.
           Infected T lymphocytes that are transformed by HTLV-1 into malignant ATL cell have
           constitutively activated Interleukin-2 (IL-2), IL-9 and IL-15 production pathways that
           function as autocrine and paracrine stimulators of these cells by stimulating these
           cells through the Janus Kinase (JAK) 1 and 3/Signal transducer and activator of
           transcription 5 (STAT5) pathways.

        -  Ruxolitinib is a drug that has been approved to treat bone marrow disorders. Ruxolitinib
           is a tyrosine kinase inhibitor that disrupts signaling through the JAK 1 and 2/STAT3 and
           5 pathways and have potential as a treatment for ATL. Researchers want to see if
           ruxolitinib can be a safe and effective treatment for ATL.

        -  Initially this trial was designed as a single dose level phase II trial with ruxolitinib
           given at the dose approved for the treatment of primary myelofibrosis, post-polycythemia
           vera myelofibrosis and post-essential thrombocythemia myelofibrosis.

        -  Clinical and correlative laboratory data demonstrated limited inhibition and impact on
           the subject's disease with the standard 20 mg twice daily dose. Given that the
           manufacturers of ruxolitinib had safety data for administering ruxolitinib to normal
           healthy volunteers at doses up to 50 mg twice or 100 mg once daily, the trial was
           reconfigured as a phase I dose escalation trial giving these higher doses on the twice
           daily schedule

      Objectives:

      Initial Phase II design:

        -  Define clinical or objective response rate for the 20 mg twice daily dose of
           Ruxolitinib.

        -  Define safety profile, Time to progression and survival time.

      Subsequent Phase I dose escalation with expansion cohort treated at the MTD or MAD:

        -  Determine the maximum tolerated dose (MTD) and clinical response rate for ruxolitinib
           administered at the higher dose levels.

        -  Determine safety profile, time to progression

        -  To test the safety and effectiveness of ruxolitinib for adult T-cell leukemia.

      Eligibility:

      - Individuals at least 18 years of age who have ATL caused by HTLV-1.

      Design:

        -  Participants will be screened with a physical exam and medical history. Blood and urine
           samples will be collected. Imaging studies will also be performed.

        -  Participants will take ruxolitinib twice a day for 28 days. They will have blood tests
           on days 1, 14, and 28. These tests will look at the levels of HTLV-1 in the blood.
           Participants will have a final blood test about 2 weeks later. Treatment will also be
           monitored with imaging studies.

        -  Participants who have a partial response during treatment may be able to start taking
           ruxolitinib again after the final blood test. They will continue to take ruxolitinib for
           as long as it is effective and the side effects are not severe.

        -  Participants who have a full response during treatment will take ruxolitinib for 56 more
           days, and then stop treatment. If ATL returns, they may restart treatment and continue
           it for as long as it is effective.
Background:

        -  Adult T-cell leukemia is a lymphoproliferative disorder characterized by the presence of
           cluster of differentiation 4 (CD4)/cluster of differentiation 25 (CD25) expressing T
           cells (interleukin-2 receptor (IL-2R) alpha expressing) in the peripheral blood, in
           lymphoid and other tissues.

        -  In smoldering and chronic adult T-cell leukemia (ATL) the human T-cell leukemia virus 1
           (HTLV-1) encoded protein, Tax constitutively activates interleukin-2 (IL-2), IL-9 and
           IL-15 autocrine/paracrine systems that in turn activate the Janus kinase
           (JAK)-1/3/signal transducer and activator of transcription 5 (STAT5) pathways.

        -  Ruxolitinib a therapeutic agent inhibits cytokine mediated Janus kinase (JAK)-1/2
           activation and ex vivo proliferation of malignant T cells from subjects with ATL.

        -  Ruxolitinib is a potent orally bioavailable JAK1/2 inhibitor not licensed for the
           treatment of ATL.

      Primary Objective:

      Objective Initial Phase II:

        -  To determine clinical or objective response rate for ruxolitinib given at 20 mg twice
           daily

        -  Primary Objective Dose Escalation Phase I: To determine the maximum tolerated dose and
           clinical response rate for ruxolitinib given at doses of 30, 40 or 50 mg orally twice
           daily in subjects with smoldering, chronic and biologically indolent acute or
           lymphomatous subtype of ATL

      Eligibility

        -  Subjects greater than or equal to 18 years old with pathologically confirmed adult
           T-cell leukemia: smoldering or chronic or previously treated lymphomatous or acute
           subtypes with clinically indolent behavior indicated by lack of significant symptoms and
           treatment free interval of greater than 6 months.

        -  Subjects must have measurable or evaluable disease. Subjects with > 10% of their PBMCs
           having the characteristic abnormal (i.e., CD3dim, CD4 plus CD25 plus expressing)
           fluorescence activated cell sorting (FACS) profile for circulating ATL cells will be
           considered to have measurable disease.

        -  Subjects with symptomatic leukemic meningitis, bony or gastrointestinal (GI) tract
           involvement, serum calcium or Lactate dehydrogenase (LDH) > 1.5 times the upper limit of
           normal will be excluded. However, subjects that have both ATL and another HTLV-1
           associated disease such as tropical spastic paraparesis (human T-cell leukemia virus 1
           (HTLV-1) Associated Myelopathy (HAM)/tropical spastic paraparesis (TSP)) will be
           included.

        -  No prior treatment with another JAK inhibitor; subjects previously treated in this
           protocol at the lower dose are eligible to restart treatment at the higher dose levels.

      Design

      - This is a pilot open-label, trial with off label-use of oral ruxolitinib that will treat 27
      to 33 Subjects with smoldering or chronic or clinically indolent ATL. Groups of 3 to 6 newly
      enrolled or reenrolled Subjects will begin treatment at an elevated dose of 30 mg orally
      given twice daily. If this dose is tolerated without exceeding the criteria for dose limiting
      toxicity (DLT) during the first cycle of treatment, the tolerability of treatment at 40 mg
      and then 50 mg twice daily will be evaluated.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Phase II: Best Response
time frame: From the time of the start of treatment to approximately 3 years of 5
description: Best response is complete response (CR) plus partial response (PR). Response was measured by the Revised Response Criteria for Lymphoma by Cheson, et al, and the International Consensus Meeting Criteria for Adult T-Cell Lymphoma (ATL). Complete response is disappearance of all clinical, microscopic, and radiographic evidence of disease. Partial response is a ≥50% reduction in the sum of the products of the greatest diameters of measurable disease without the appearance of new lesion. Stable disease is failure to attain complete response, partial response, or progressive disease. Progressive disease in peripheral blood is defined by a 50% increase from nadir in the count of flower cells and an absolute lymphocyte count, including flower cells, of 4x10^9/L; or the appearance of new lesions excluding skin.
measure: Phase I: Maximum Tolerated Dose (MTD)
time frame: From the time of the start of treatment to approximately 1 year
description: MTD is defined as the dose level at which no more than 1 of up to 6 participants experience dose-limiting toxicity (DLT) during the first cycle (28 days) treatment, and the dose below that at which at least 2 (of ≤6) participants have DLT as a result of the drug. A DLT is any grade 3 or 4 toxicity, if deemed possibly, probably, or definitely related to the study drug by the principal investigator during the first cycle of treatment with some exceptions such as Grade 3 anemia without hemolysis. Grade 3 or 4 granulocytopenia or leukopenia without infection, Grade 3 thrombocytopenia without bleeding, and Grade 3 or 4 lymphopenia. Grade 3 is severe or medically significant. Grade 4 is life-threatening, urgent intervention indicated.
measure: Phase II: Time to Progression (TTP)
time frame: From the time of the start of treatment to approximately 3 years
description: TTP is defined as the date of protocol consent until date of progressive disease is documented. Progressive disease was assessed by the Revised Response Criteria for Lymphoma by Cheson, et al, and the International Consensus Meeting Criteria for Adult T-Cell Lymphoma (guideline (version 1.1). Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, and the appearance of one or more new lesions.
measure: Phase II: Survival Time
time frame: From the time of the start of treatment to approximately 3 years
description: Survival time is defined as the date of protocol consent until the date of the subject's death for any cause.
measure: Phase I: Grade of Serious and/or Non-serious Adverse Events (SAEs) Related to the Experimental Treatment by Grade
time frame: From the time of the start of treatment to approximately 1 year
description: Grade of serious adverse events (SAEs) related to the experimental treatment. Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, and Grade 4 is life-threatening.
measure: Phase I: Time to Progression When Ruxolitinib is Administered at Doses of 30, 40 or 50 mg Orally Twice Daily
time frame: From the time of the start of treatment to approximately 1 year
description: TTP is defined as the date of protocol consent until date of progressive disease is documented. Progressive disease was assessed by the Revised Response Criteria for Lymphoma by Cheson, et al, and the International Consensus Meeting Criteria for Adult T-Cell Lymphoma guidelines (version 1.1). Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, and the appearance of one or more new lesions.
measure: Number of Participants With a Dose Limiting Toxicity (DLT)
time frame: During the first cycle of treatment (28 days)
description: A DLT is any grade 3 or 4 toxicity, if deemed possibly, probably or definitely related to the study drug by the principal investigator during the first cycle of treatment with some exceptions such as Grade 3 anemia without hemolysis. Grade 3 or 4 granulocytopenia or leukopenia without infection, Grade 3 thrombocytopenia without bleeding, and Grade 3 or 4 lymphopenia. Grade 3 is severe or medically significant. Grade 4 is life-threatening, urgent intervention indicated.
measure: Number of Participants With Non-Serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0).
time frame: Date treatment consent signed to date off study, approximately 110 months and 27 days.
description: Here is the number of participants with non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence.
arm group label: Original Phase II Standard Ruxolitinib dose cohort
arm group type: Experimental
description: Ruxolitinib 20 mg orally twice daily for 28 days. Subjects may continue to receive treatment until progressive disease (PD) or unacceptable toxicity.
arm group label: 2- Phase 1 Dose Escalation cohorts
arm group type: Experimental
description: Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.
Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.
Dose level 3: Ruxolitinib: Ruxolitinib 50 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.
arm group label: 3- Phase 1 Dose Expansion Cohort
arm group type: Experimental
description: Ruxolitinib at the maximum tolerated dose (MTD) or the maximum administered dose (MAD) defined in the phase 1 dose escalation cohorts. Subjects may continue to receive treatment until progressive disease (PD) or unacceptable toxicity.
intervention type: Drug
intervention name: Ruxolitinib
description: Ruxolitinib 20 mg orally twice daily for 28 days. Subjects may continue to receive treatment until progressive disease (PD) or unacceptable toxicity.
arm group label: 3- Phase 1 Dose Expansion Cohort
arm group label: Original Phase II Standard Ruxolitinib dose cohort
other name: Jakafi
intervention type: Drug
intervention name: Ruxolitinib
description: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.
arm group label: 2- Phase 1 Dose Escalation cohorts
other name: Jakafi
intervention type: Drug
intervention name: Ruxolitinib
description: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.
arm group label: 2- Phase 1 Dose Escalation cohorts
other name: Jakafi
intervention type: Drug
intervention name: Ruxolitinib
description: Ruxolitinib 50 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.
arm group label: 2- Phase 1 Dose Escalation cohorts
other name: Jakafi
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Kevin C Conlon, M.D.
role: Principal Investigator
affiliation: National Cancer Institute (NCI)
facility: 
country: United States
url: https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2013-C-0006.html
description: NIH Clinical Center Detailed Web Page
citation: Matsuoka M, Jeang KT. Human T-cell leukemia virus type 1 (HTLV-1) and leukemic transformation: viral infectivity, Tax, HBZ and therapy. Oncogene. 2011 Mar 24;30(12):1379-89. doi: 10.1038/onc.2010.537. Epub 2010 Nov 29.
PMID: 21119600
citation: Tsukasaki K, Hermine O, Bazarbachi A, Ratner L, Ramos JC, Harrington W Jr, O'Mahony D, Janik JE, Bittencourt AL, Taylor GP, Yamaguchi K, Utsunomiya A, Tobinai K, Watanabe T. Definition, prognostic factors, treatment, and response criteria of adult T-cell leukemia-lymphoma: a proposal from an international consensus meeting. J Clin Oncol. 2009 Jan 20;27(3):453-9. doi: 10.1200/JCO.2008.18.2428. Epub 2008 Dec 8.
PMID: 19064971
citation: Yamada Y, Atogami S, Hasegawa H, Kamihira S, Soda M, Satake M, Yamaguchi K. [Nationwide survey of adult T-cell leukemia/lymphoma (ATL) in Japan]. Rinsho Ketsueki. 2011 Nov;52(11):1765-71. Japanese.
PMID: 22185799
responsible party type: Principal Investigator
investigator affiliation: National Cancer Institute (NCI)
investigator full name: Kevin Conlon, MD
investigator title: Principal Investigator
mesh term: Leukemia
mesh term: Leukemia, T-Cell
mesh term: Leukemia-Lymphoma, Adult T-Cell
sharing ipd: Yes
ipd description: All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request.
All collected IPD will be shared with collaborators under the terms of collaborative agreements.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd time frame: Clinical data available during the study and indefinitely.
ipd access criteria: Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI).
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 