<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/NCT01688466</url>
  </required_header>
  <id_info>
    <org_study_id>120197</org_study_id>
    <secondary_id>12-C-0197</secondary_id>
    <nct_id>NCT01688466</nct_id>
  </id_info>
  <brief_title>Pomalidomide for Chronic Graft-versus-Host Disease</brief_title>
  <official_title>A Randomized Phase 2 Single-Center Study of Pomalidomide for Chronic GvHD</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background:&#xD;
&#xD;
      - Pomalidomide is a drug that alters the body's immune response. It may help people who have&#xD;
      chronic graft-versus-host disease (GvHD). GvHD may appear after a stem cell transplant, when&#xD;
      immune cells in the transplant try to attack tissues in the person who received the&#xD;
      transplant. GvHD is not easy to treat, and often does not respond to standard treatments.&#xD;
      Researchers want to see if pomalidomide is a safe and effective treatment for GvHD.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
      - To test the safety and effectiveness of pomalidomide for GvHD that has not responded to&#xD;
      standard treatments.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
      - Individuals at least 18 years of age who have GvHD that has not responded to standard&#xD;
      treatments.&#xD;
&#xD;
      Design:&#xD;
&#xD;
        -  Participants will be screened with a physical exam and medical history. Blood and urine&#xD;
           samples will also be collected. A lung function test and imaging studies will also be&#xD;
           given.&#xD;
&#xD;
        -  Participants will take pomalidomide capsules once a day for 4-week periods called&#xD;
           cycles.&#xD;
&#xD;
        -  Treatment will be monitored with frequent blood tests and imaging studies. Saliva&#xD;
           samples and skin and mouth tissue biopsies will also be collected during treatment.&#xD;
&#xD;
        -  Treatment will continue for six cycles (6 months), unless the GvHD gets worse or side&#xD;
           effects are too severe. If the GvHD has improved at the end of the six cycles,&#xD;
           participants may be able to continue to take pomalidomide for up to six more cycles.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      BACKGROUND:&#xD;
&#xD;
        -  Chronic graft-versus-host disease (cGvHD) is the leading cause of non-relapse morbidity&#xD;
           and mortality in persons after allogeneic hematopoietic cell transplants.&#xD;
&#xD;
        -  About 50% of persons with cGvHD have disease refractory to systemic corticosteroids and&#xD;
           there is no standard second-line therapy.&#xD;
&#xD;
        -  Thalidomide, a drug with immune-modulating effects, was active in advanced cGvHD but was&#xD;
           difficult to use at appropriate doses.&#xD;
&#xD;
        -  Pomalidomide is related to thalidomide but with higher potency and more favorable&#xD;
           toxicity profile. It is active in multiple myeloma and myeloproliferative neoplasm&#xD;
           associated myelofibrosis. Preliminary data in humans with cGvHD are encouraging but data&#xD;
           are limited.&#xD;
&#xD;
      OBJECTIVES:&#xD;
&#xD;
      - Primary: Determine whether pomalidomide is effective in persons with moderate or severe&#xD;
      cGvHD not controlled by corticosteroids.&#xD;
&#xD;
      ELIGIBILITY:&#xD;
&#xD;
      Inclusion Criteria&#xD;
&#xD;
        -  Moderate or severe cGvHD per National Institutes of Health (NIH) criteria&#xD;
&#xD;
        -  Age 18 to 75 years old&#xD;
&#xD;
        -  Karnofsky performance score greater than or equal to 60%&#xD;
&#xD;
        -  Has cGvHD that did not respond to high-dose corticosteroids (average 0.5 mg/kg/d&#xD;
           prednisone for greater than or equal to 8 weeks) or second-line therapy&#xD;
&#xD;
        -  Receiving stable or tapering doses of systemic therapy in the preceding 4 weeks&#xD;
&#xD;
        -  Agree to adhere to methods of contraception and other fertility control measures as&#xD;
           prescribed by the protocol&#xD;
&#xD;
      Exclusion Criteria&#xD;
&#xD;
        -  Acute GvHD (classic and late per NIH criteria)&#xD;
&#xD;
        -  Absolute neutrophils &lt;1.0x10(9)/L, platelets &lt;75x10(9)/L, estimated creatinine clearance&#xD;
           &lt;50 mL/min/1.73m(2)&#xD;
&#xD;
        -  NIH lung score 3&#xD;
&#xD;
        -  Pregnant or lactating&#xD;
&#xD;
        -  Uncontrolled infection&#xD;
&#xD;
      DESIGN:&#xD;
&#xD;
      Randomized phase 2 trial with the single stage selection design. Patients will receive either&#xD;
      a constant low dose of pomalidomide (0.5 mg/day) for six months or a strategy of increasing&#xD;
      dose of pomalidomide from 0.5 mg/d up through each individual patient's maximum tolerated&#xD;
      dose, with escalations by 0.5 mg/d every 2 weeks to a maximum of 2.0 mg/d. As an early&#xD;
      stopping rule for futility, if after 7 patients have enrolled on either arm, 0 have&#xD;
      responded, then no further patients will be accrued to that arm as soon as this can be&#xD;
      determined. To protect patient safety, an early stopping rule will be implemented. With two&#xD;
      arms, each of which has a maximal accrual of 16 patients, up to 32 evaluable patients will be&#xD;
      randomized. Response assessments will occur every 3 months with primary efficacy endpoint&#xD;
      evaluated at 6 months. Patients with responding disease will continue therapy for another 6&#xD;
      months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 30, 2012</start_date>
  <completion_date type="Actual">March 31, 2019</completion_date>
  <primary_completion_date type="Actual">March 30, 2017</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall Response at 6 Months</measure>
    <time_frame>6 months</time_frame>
    <description>Overall response was assessed by the National Institutes of Health (NIH) Chronic Graft-Versus Host Disease (cGVHD) Response criteria. Complete response (CR) is complete resolution in all signs and symptoms at all affected organs or tissues. Partial response (PR) is improvement in ≥ 1 organ or tissue with no progression in any other affected organ or tissue. Response &lt; PR is a change towards improvement from the pre-treatment baseline but not meeting the criteria for CR or PR. Stable disease (SD) is no change in cGVHD. Flare is exacerbation of cGVHD manifestations during withdrawal of immunosuppressive therapy which do not exceed those at the beginning of the trial and improves after reinstatement of previous treatment. Progressive disease (PD) is failure of therapy to control cGVHD . Mixed response (improvement in some organs but worsening in others) will be categorized as progressive disease.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Toxicity</measure>
    <time_frame>50 months and 20 days</time_frame>
    <description>Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">34</enrollment>
  <condition>Graft vs Host Disease</condition>
  <condition>Graft-Versus-Host Disease</condition>
  <arm_group>
    <arm_group_label>0.5 mg/day with Dose Escalation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>0.5 mg/day with Dose Escalation by 0.5 mg/day increments every 2 weeks to a maximum of 2.0 mg/day</description>
  </arm_group>
  <arm_group>
    <arm_group_label>0.5 mg/day without Dose Escalation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>0.5 mg/day without Dose Escalation</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pomalidomide</intervention_name>
    <description>0.5 mg/day with and/or without Dose Escalation and 0.5 mg/day- 2.0 mg/day by mouth (PO) QD(every day) of each 28 day cycle</description>
    <arm_group_label>0.5 mg/day with Dose Escalation</arm_group_label>
    <arm_group_label>0.5 mg/day without Dose Escalation</arm_group_label>
    <other_name>POMALYST</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA&#xD;
&#xD;
          -  Moderate or severe chronic graft-versus-host disease (cGvHD) diagnosed and staged per&#xD;
             National Institutes of Health (NIH) criteria&#xD;
&#xD;
          -  Greater than or equal to18-75 years of age, because no dosing or adverse event data&#xD;
             are currently available on the use of pomalidomide in persons greater than or equal&#xD;
             to18 years of age&#xD;
&#xD;
          -  Has cGvHD that did not respond to high-dose corticosteroids (average 0.5 mg/kg/d&#xD;
             prednisone for &gt;8 weeks) or second-line systemic therapy&#xD;
&#xD;
          -  If taking systemic therapy for cGvHD at the time of enrollment, must be on a stable or&#xD;
             tapering schedule in the preceding 4 weeks (extracorporeal photopheresis has to be&#xD;
             stopped at least by 4 weeks before enrollment)&#xD;
&#xD;
          -  Karnofsky performance score greater than or equal to 60%&#xD;
&#xD;
          -  Life expectancy &gt;3 months&#xD;
&#xD;
          -  Stable primary malignancy for previous 3 months&#xD;
&#xD;
          -  Agree to adhere to methods of contraception and other fertility control measures as&#xD;
             prescribed by the protocol&#xD;
&#xD;
          -  Because agents of this class are known to be teratogenic, women of childbearing&#xD;
             potential and men must agree to use effective forms of contraception (hormonal or&#xD;
             barrier method of birth control; abstinence) prior to study entry and for the duration&#xD;
             of study participation. Should a woman become pregnant or suspect she is pregnant&#xD;
             while she or her partner is participating in this study, she should inform her&#xD;
             treating physician immediately.&#xD;
&#xD;
          -  Females of childbearing potential (FCBP) (Cross) must have a negative serum or urine&#xD;
             pregnancy test with a sensitivity of at least 25 mIU/mL within 10&#xD;
&#xD;
             14 days prior to and again within 24 hours of starting pomalidomide and must either&#xD;
             commit to continued abstinence from heterosexual intercourse or begin TWO acceptable&#xD;
             methods of birth control, one highly effective method and one additional effective&#xD;
             method AT THE SAME TIME, at least 28 days before she starts taking pomalidomide. FCBP&#xD;
             must also agree to ongoing pregnancy testing. Men must agree to use a latex condom&#xD;
             during sexual contact with a FCBP even if they have had a vasectomy. All patients must&#xD;
             be counseled at a minimum of every 28 days about pregnancy precautions and risks of&#xD;
             fetal exposure. Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable&#xD;
             Birth Control Methods, AND Education and Counseling Guidance Document.&#xD;
&#xD;
          -  Male Subjects&#xD;
&#xD;
          -  Must agree to use a latex condom during sexual contact with females of childbearing&#xD;
             potential while participating in the study and for at least 28 days following&#xD;
             discontinuation of study drug even if he has undergone a successful vasectomy&#xD;
&#xD;
          -  Will be warned that sharing study drug is prohibited and will be counseled about&#xD;
             pregnancy precautions and potential risks of fetal exposure&#xD;
&#xD;
          -  Must agree to abstain from donating blood, semen, or sperm during study participation&#xD;
             and for at least 28 days after discontinuation of study drug.&#xD;
&#xD;
          -  Must agree that if a pregnancy or a positive pregnancy test does occur in a study&#xD;
             subject or the partner of a male study subject during study participation, study drug&#xD;
             must be immediately discontinued.&#xD;
&#xD;
          -  Patients must agree to not share study drug with anyone during participation in the&#xD;
             study.&#xD;
&#xD;
          -  Ability of subject to understand and the willingness to sign a written informed&#xD;
             consent document.&#xD;
&#xD;
          -  All study participants must be registered into the mandatory POMALYST REMS (TM)&#xD;
             program, and be willing and able to comply with the requirements of the POMALYST REMS&#xD;
             (TM) program.&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
          -  Acute GvHD, classic (less than or equal to day 100) or late-onset (&gt;day 100)&#xD;
&#xD;
          -  Systemic immune suppression or systemic therapy for cGvHD started within preceding 4&#xD;
             weeks including extracorporeal photopheresis&#xD;
&#xD;
          -  Hypersensitivity to thalidomide, lenalidomide or pomalidomide&#xD;
&#xD;
          -  Any serious medical condition which places the subject at an unacceptable risk if he&#xD;
             or she were to participate in the study or confounds the ability to interpret data&#xD;
             from the study, including, but not limited to, symptomatic congestive heart failure,&#xD;
             unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations&#xD;
             that would limit compliance with study requirements.&#xD;
&#xD;
          -  Neutrophil &lt;1.0x10(9)/L, platelets &lt;75x10(9)/L, estimated creatinine clearance &lt;50&#xD;
             mL/min/1.73m(2) (Cockroft-Gault formula) total bilirubin &gt;3 mg/dL, transaminase&gt;3xUNL&#xD;
&#xD;
          -  Uncontrolled infection&#xD;
&#xD;
          -  Active human immunodeficiency virus 1 (HIV-1), hepatitis B virus (HBV) and/or&#xD;
             hepatitis C virus (HCV) infection&#xD;
&#xD;
        Uncontrolled arrhythmias or symptomatic heart disease or left ventricular ejection fraction&#xD;
        (LVEF) &lt;45%&#xD;
&#xD;
          -  Other cancer except that for which the transplant was done &lt;2 years before study&#xD;
             entry, except non-melanoma skin cancer or carcinoma in situ of the uterine cervix or&#xD;
             breast&#xD;
&#xD;
          -  Taking other investigational drugs&#xD;
&#xD;
          -  NIH lung score 3&#xD;
&#xD;
          -  Pregnant women are excluded from this study because pomalidomide has potential for&#xD;
             teratogenic effects. Because there is an unknown but potential risk for adverse events&#xD;
             in nursing infants secondary to treatment of the mother with pomalidomide,&#xD;
             breastfeeding must be discontinued while the mother is taking study drug and for at&#xD;
             least 28 days after discontinuation of study drug. These potential risks may also&#xD;
             apply to other agents used in this study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Steven Z Pavletic, 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_2012-C-0197.html</url>
    <description>NIH Clinical Center Detailed Web Page</description>
  </link>
  <reference>
    <citation>Bolanos-Meade J, Vogelsang GB. Chronic graft-versus-host disease. Curr Pharm Des. 2008;14(20):1974-86. doi: 10.2174/138161208785061373.</citation>
    <PMID>18691108</PMID>
  </reference>
  <reference>
    <citation>Lee SJ, Vogelsang G, Flowers ME. Chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2003 Apr;9(4):215-33. doi: 10.1053/bbmt.2003.50026.</citation>
    <PMID>12720215</PMID>
  </reference>
  <reference>
    <citation>Martin PJ, Weisdorf D, Przepiorka D, Hirschfeld S, Farrell A, Rizzo JD, Foley R, Socie G, Carter S, Couriel D, Schultz KR, Flowers ME, Filipovich AH, Saliba R, Vogelsang GB, Pavletic SZ, Lee SJ; Design of Clinical Trials Working Group. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: VI. Design of Clinical Trials Working Group report. Biol Blood Marrow Transplant. 2006 May;12(5):491-505. doi: 10.1016/j.bbmt.2006.03.004.</citation>
    <PMID>16635784</PMID>
  </reference>
  <verification_date>June 2019</verification_date>
  <study_first_submitted>September 15, 2012</study_first_submitted>
  <study_first_submitted_qc>September 15, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 20, 2012</study_first_posted>
  <results_first_submitted>December 21, 2017</results_first_submitted>
  <results_first_submitted_qc>December 28, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">January 23, 2018</results_first_posted>
  <last_update_submitted>June 4, 2019</last_update_submitted>
  <last_update_submitted_qc>June 4, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">June 18, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>National Cancer Institute (NCI)</investigator_affiliation>
    <investigator_full_name>Steven Pavletic, M.D.</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Immune Modulatory</keyword>
  <keyword>Systemic Absorption</keyword>
  <keyword>Oral Agent</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Graft vs Host Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pomalidomide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol, Statistical Analysis Plan, and Informed Consent Form: Protocol and Consent and SAP</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>May 17, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/66/NCT01688466/Prot_SAP_ICF_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan: Updated Protocol and SAP</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>September 14, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/66/NCT01688466/Prot_SAP_001.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form: Updated Standard Consent</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>October 25, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/66/NCT01688466/ICF_002.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>0.5 mg/Day With Dose Escalation</title>
          <description>0.5 mg/day with Dose Escalation by 0.5 mg/day increments every 2 weeks to a maximum of 2.0 mg/day&#xD;
Pomalidomide: 0.5 mg/day with and/or without Dose Escalation and 0.5 mg/day- 2.0 mg/day by mouth (PO) QD(every day) of each 28 day cycle</description>
        </group>
        <group group_id="P2">
          <title>0.5 mg/Day Without Dose Escalation</title>
          <description>0.5 mg/day without Dose Escalation&#xD;
Pomalidomide: 0.5 mg/day with and/or without Dose Escalation and 0.5 mg/day- 2.0 mg/day by mouth (PO) QD(every day) of each 28 day cycle</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
                <participants group_id="P2" count="17"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Not evaluable</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>0.5 mg/Day With Dose Escalation</title>
          <description>0.5 mg/day with Dose Escalation by 0.5 mg/day increments every 2 weeks to a maximum of 2.0 mg/day&#xD;
Pomalidomide: 0.5 mg/day with and/or without Dose Escalation and 0.5 mg/day- 2.0 mg/day by mouth (PO) QD(every day) of each 28 day cycle</description>
        </group>
        <group group_id="B2">
          <title>0.5 mg/Day Without Dose Escalation</title>
          <description>0.5 mg/day without Dose Escalation&#xD;
Pomalidomide: 0.5 mg/day with and/or without Dose Escalation and 0.5 mg/day- 2.0 mg/day by mouth (PO) QD(every day) of each 28 day cycle</description>
        </group>
        <group group_id="B3">
          <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="17"/>
            <count group_id="B2" value="17"/>
            <count group_id="B3" value="34"/>
          </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_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="30"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                  </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="48.5" spread="14.2"/>
                    <measurement group_id="B2" value="46.8" spread="13.9"/>
                    <measurement group_id="B3" value="47.65" spread="14.05"/>
                  </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="7"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="22"/>
                  </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_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_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_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </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_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Mexican, Puerto Rican, Cuban, Central/So. American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not meeting definition for Hispanic or Latino</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Overall Response at 6 Months</title>
        <description>Overall response was assessed by the National Institutes of Health (NIH) Chronic Graft-Versus Host Disease (cGVHD) Response criteria. Complete response (CR) is complete resolution in all signs and symptoms at all affected organs or tissues. Partial response (PR) is improvement in ≥ 1 organ or tissue with no progression in any other affected organ or tissue. Response &lt; PR is a change towards improvement from the pre-treatment baseline but not meeting the criteria for CR or PR. Stable disease (SD) is no change in cGVHD. Flare is exacerbation of cGVHD manifestations during withdrawal of immunosuppressive therapy which do not exceed those at the beginning of the trial and improves after reinstatement of previous treatment. Progressive disease (PD) is failure of therapy to control cGVHD . Mixed response (improvement in some organs but worsening in others) will be categorized as progressive disease.</description>
        <time_frame>6 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>0.5 mg/Day With Dose Escalation</title>
            <description>0.5 mg/day with Dose Escalation by 0.5 mg/day increments every 2 weeks to a maximum of 2.0 mg/day&#xD;
Pomalidomide: 0.5 mg/day with and/or without Dose Escalation and 0.5 mg/day- 2.0 mg/day by mouth (PO) QD(every day) of each 28 day cycle</description>
          </group>
          <group group_id="O2">
            <title>0.5 mg/Day Without Dose Escalation</title>
            <description>0.5 mg/day without Dose Escalation&#xD;
Pomalidomide: 0.5 mg/day with and/or without Dose Escalation and 0.5 mg/day- 2.0 mg/day by mouth (PO) QD(every day) of each 28 day cycle</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Response at 6 Months</title>
          <description>Overall response was assessed by the National Institutes of Health (NIH) Chronic Graft-Versus Host Disease (cGVHD) Response criteria. Complete response (CR) is complete resolution in all signs and symptoms at all affected organs or tissues. Partial response (PR) is improvement in ≥ 1 organ or tissue with no progression in any other affected organ or tissue. Response &lt; PR is a change towards improvement from the pre-treatment baseline but not meeting the criteria for CR or PR. Stable disease (SD) is no change in cGVHD. Flare is exacerbation of cGVHD manifestations during withdrawal of immunosuppressive therapy which do not exceed those at the beginning of the trial and improves after reinstatement of previous treatment. Progressive disease (PD) is failure of therapy to control cGVHD . Mixed response (improvement in some organs but worsening in others) will be categorized as progressive disease.</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="17"/>
                <count group_id="O2" value="17"/>
              </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_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Partial Response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Progressive Disease</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Stable Disease</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mixed Response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Response &lt; Partial Response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Flare</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Did not respond to treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not Evaluable</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Toxicity</title>
        <description>Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.</description>
        <time_frame>50 months and 20 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>0.5 mg/Day With Dose Escalation</title>
            <description>0.5 mg/day with Dose Escalation by 0.5 mg/day increments every 2 weeks to a maximum of 2.0 mg/day&#xD;
Pomalidomide: 0.5 mg/day with and/or without Dose Escalation and 0.5 mg/day- 2.0 mg/day by mouth (PO) QD(every day) of each 28 day cycle</description>
          </group>
          <group group_id="O2">
            <title>0.5 mg/Day Without Dose Escalation</title>
            <description>0.5 mg/day without Dose Escalation&#xD;
Pomalidomide: 0.5 mg/day with and/or without Dose Escalation and 0.5 mg/day- 2.0 mg/day by mouth (PO) QD(every day) of each 28 day cycle</description>
          </group>
        </group_list>
        <measure>
          <title>Toxicity</title>
          <description>Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.</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="17"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17"/>
                    <measurement group_id="O2" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>50 months and 20 days</time_frame>
      <group_list>
        <group group_id="E1">
          <title>0.5 mg/Day With Dose Escalation</title>
          <description>0.5 mg/day with Dose Escalation by 0.5 mg/day increments every 2 weeks to a maximum of 2.0 mg/day&#xD;
Pomalidomide: 0.5 mg/day with and/or without Dose Escalation and 0.5 mg/day- 2.0 mg/day by mouth (PO) QD(every day) of each 28 day cycle</description>
        </group>
        <group group_id="E2">
          <title>0.5 mg/Day Without Dose Escalation</title>
          <description>0.5 mg/day without Dose Escalation&#xD;
Pomalidomide: 0.5 mg/day with and/or without Dose Escalation and 0.5 mg/day- 2.0 mg/day by mouth (PO) QD(every day) of each 28 day cycle</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="17"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Chest pain - cardiac</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Sinus bradycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Retinopathy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Duodenal ulcer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders - Other, specify</sub_title>
                <description>Gastroenteritis</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchial infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Infections and infestations - Other, specify</sub_title>
                <description>CMV reactivation</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
                <counts group_id="E2" events="6" subjects_affected="5" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Salivary gland infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="4" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Wound infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Carbon monoxide diffusing capacity decreased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Generalized muscle weakness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Muscle weakness lower limb</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </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="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Thromboembolic event</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </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="17" subjects_at_risk="17"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="17"/>
              </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="3" subjects_affected="2" subjects_at_risk="17"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Hemolysis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac disorders - Other, specify</sub_title>
                <description>ST depression</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Sinus bradycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Hearing impaired</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blurred vision</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Dry eye</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Glaucoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Photophobia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Retinal vascular disorder</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="17"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Esophageal ulcer</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Gastroesophageal reflux disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders - Other, specify</sub_title>
                <description>reflux + fullness</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="17"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Oral pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="17"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="11" subjects_affected="10" subjects_at_risk="17"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Flu like symptoms</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Immune system disorders - Other, specify</sub_title>
                <description>throat tightness, dry mouth, pruritis</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchial infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Infections and infestations - Other, specify</sub_title>
                <description>CMV reactivation</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="17"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" events="4" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Spinal fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" events="14" subjects_affected="10" subjects_at_risk="17"/>
                <counts group_id="E2" events="9" subjects_affected="8" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Lymphocyte count increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="8" subjects_affected="6" subjects_at_risk="17"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="17"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Hypermagnesemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Hyperuricemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <counts group_id="E1" events="10" subjects_affected="9" subjects_at_risk="17"/>
                <counts group_id="E2" events="5" subjects_affected="4" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Generalized muscle weakness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Joint range of motion decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Joint range of motion decreased cervical spine</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Musculoskeletal and connective tissue disorder - Other, specify</sub_title>
                <description>L. plantar fascilitis</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Myositis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Amnesia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Dysesthesia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Dysphasia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Memory impairment</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Urinary frequency</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Testicular pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Vaginal inflammation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Forced expiratory volume decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Upper respiratory infection</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="17"/>
                <counts group_id="E2" events="14" subjects_affected="9" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Bullous dermatitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Pain of skin</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="5" subjects_affected="3" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="17"/>
                <counts group_id="E2" events="7" subjects_affected="5" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other, specify</sub_title>
                <description>increased plaques</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other, specify</sub_title>
                <description>leg wounds</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other, specify</sub_title>
                <description>upper extremity, neck tightness</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Skin ulceration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="5" subjects_affected="3" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </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>Dr. Steven Z. Pavletic</name_or_title>
      <organization>National cancer Institute</organization>
      <phone>301-402-4899</phone>
      <email>steven_pavletic@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/NCT01688466
org study id: 120197
secondary id: 12-C-0197
nct id: NCT01688466
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
Background:

      - Pomalidomide is a drug that alters the body's immune response. It may help people who have
      chronic graft-versus-host disease (GvHD). GvHD may appear after a stem cell transplant, when
      immune cells in the transplant try to attack tissues in the person who received the
      transplant. GvHD is not easy to treat, and often does not respond to standard treatments.
      Researchers want to see if pomalidomide is a safe and effective treatment for GvHD.

      Objectives:

      - To test the safety and effectiveness of pomalidomide for GvHD that has not responded to
      standard treatments.

      Eligibility:

      - Individuals at least 18 years of age who have GvHD that has not responded to standard
      treatments.

      Design:

        -  Participants will be screened with a physical exam and medical history. Blood and urine
           samples will also be collected. A lung function test and imaging studies will also be
           given.

        -  Participants will take pomalidomide capsules once a day for 4-week periods called
           cycles.

        -  Treatment will be monitored with frequent blood tests and imaging studies. Saliva
           samples and skin and mouth tissue biopsies will also be collected during treatment.

        -  Treatment will continue for six cycles (6 months), unless the GvHD gets worse or side
           effects are too severe. If the GvHD has improved at the end of the six cycles,
           participants may be able to continue to take pomalidomide for up to six more cycles.
BACKGROUND:

        -  Chronic graft-versus-host disease (cGvHD) is the leading cause of non-relapse morbidity
           and mortality in persons after allogeneic hematopoietic cell transplants.

        -  About 50% of persons with cGvHD have disease refractory to systemic corticosteroids and
           there is no standard second-line therapy.

        -  Thalidomide, a drug with immune-modulating effects, was active in advanced cGvHD but was
           difficult to use at appropriate doses.

        -  Pomalidomide is related to thalidomide but with higher potency and more favorable
           toxicity profile. It is active in multiple myeloma and myeloproliferative neoplasm
           associated myelofibrosis. Preliminary data in humans with cGvHD are encouraging but data
           are limited.

      OBJECTIVES:

      - Primary: Determine whether pomalidomide is effective in persons with moderate or severe
      cGvHD not controlled by corticosteroids.

      ELIGIBILITY:

      Inclusion Criteria

        -  Moderate or severe cGvHD per National Institutes of Health (NIH) criteria

        -  Age 18 to 75 years old

        -  Karnofsky performance score greater than or equal to 60%

        -  Has cGvHD that did not respond to high-dose corticosteroids (average 0.5 mg/kg/d
           prednisone for greater than or equal to 8 weeks) or second-line therapy

        -  Receiving stable or tapering doses of systemic therapy in the preceding 4 weeks

        -  Agree to adhere to methods of contraception and other fertility control measures as
           prescribed by the protocol

      Exclusion Criteria

        -  Acute GvHD (classic and late per NIH criteria)

        -  Absolute neutrophils <1.0x10(9)/L, platelets <75x10(9)/L, estimated creatinine clearance
           <50 mL/min/1.73m(2)

        -  NIH lung score 3

        -  Pregnant or lactating

        -  Uncontrolled infection

      DESIGN:

      Randomized phase 2 trial with the single stage selection design. Patients will receive either
      a constant low dose of pomalidomide (0.5 mg/day) for six months or a strategy of increasing
      dose of pomalidomide from 0.5 mg/d up through each individual patient's maximum tolerated
      dose, with escalations by 0.5 mg/d every 2 weeks to a maximum of 2.0 mg/d. As an early
      stopping rule for futility, if after 7 patients have enrolled on either arm, 0 have
      responded, then no further patients will be accrued to that arm as soon as this can be
      determined. To protect patient safety, an early stopping rule will be implemented. With two
      arms, each of which has a maximal accrual of 16 patients, up to 32 evaluable patients will be
      randomized. Response assessments will occur every 3 months with primary efficacy endpoint
      evaluated at 6 months. Patients with responding disease will continue therapy for another 6
      months.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall Response at 6 Months
time frame: 6 months
description: Overall response was assessed by the National Institutes of Health (NIH) Chronic Graft-Versus Host Disease (cGVHD) Response criteria. Complete response (CR) is complete resolution in all signs and symptoms at all affected organs or tissues. Partial response (PR) is improvement in ≥ 1 organ or tissue with no progression in any other affected organ or tissue. Response < PR is a change towards improvement from the pre-treatment baseline but not meeting the criteria for CR or PR. Stable disease (SD) is no change in cGVHD. Flare is exacerbation of cGVHD manifestations during withdrawal of immunosuppressive therapy which do not exceed those at the beginning of the trial and improves after reinstatement of previous treatment. Progressive disease (PD) is failure of therapy to control cGVHD . Mixed response (improvement in some organs but worsening in others) will be categorized as progressive disease.
measure: Toxicity
time frame: 50 months and 20 days
description: Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
arm group label: 0.5 mg/day with Dose Escalation
arm group type: Experimental
description: 0.5 mg/day with Dose Escalation by 0.5 mg/day increments every 2 weeks to a maximum of 2.0 mg/day
arm group label: 0.5 mg/day without Dose Escalation
arm group type: Experimental
description: 0.5 mg/day without Dose Escalation
intervention type: Drug
intervention name: Pomalidomide
description: 0.5 mg/day with and/or without Dose Escalation and 0.5 mg/day- 2.0 mg/day by mouth (PO) QD(every day) of each 28 day cycle
arm group label: 0.5 mg/day with Dose Escalation
arm group label: 0.5 mg/day without Dose Escalation
other name: POMALYST
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Steven Z Pavletic, M.D.
role: Principal Investigator
affiliation: National Cancer Institute (NCI)
facility: 
country: United States
url: https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2012-C-0197.html
description: NIH Clinical Center Detailed Web Page
citation: Bolanos-Meade J, Vogelsang GB. Chronic graft-versus-host disease. Curr Pharm Des. 2008;14(20):1974-86. doi: 10.2174/138161208785061373.
PMID: 18691108
citation: Lee SJ, Vogelsang G, Flowers ME. Chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2003 Apr;9(4):215-33. doi: 10.1053/bbmt.2003.50026.
PMID: 12720215
citation: Martin PJ, Weisdorf D, Przepiorka D, Hirschfeld S, Farrell A, Rizzo JD, Foley R, Socie G, Carter S, Couriel D, Schultz KR, Flowers ME, Filipovich AH, Saliba R, Vogelsang GB, Pavletic SZ, Lee SJ; Design of Clinical Trials Working Group. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: VI. Design of Clinical Trials Working Group report. Biol Blood Marrow Transplant. 2006 May;12(5):491-505. doi: 10.1016/j.bbmt.2006.03.004.
PMID: 16635784
responsible party type: Principal Investigator
investigator affiliation: National Cancer Institute (NCI)
investigator full name: Steven Pavletic, M.D.
investigator title: Principal Investigator
mesh term: Graft vs Host Disease
mesh term: Pomalidomide
sharing ipd: No
provided document: 
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 