<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/NCT03257631</url>
  </required_header>
  <id_info>
    <org_study_id>CC-4047-BRN-001</org_study_id>
    <secondary_id>U1111-1199-3348</secondary_id>
    <secondary_id>2016-002903-25</secondary_id>
    <nct_id>NCT03257631</nct_id>
  </id_info>
  <brief_title>A Study of Pomalidomide Monotherapy for Children and Young Adults With Recurrent or Progressive Primary Brain Tumors</brief_title>
  <official_title>A PHASE 2 CLINICAL STUDY OF POMALIDOMIDE (CC-4047) MONOTHERAPY FOR CHILDREN AND YOUNG ADULTS WITH RECURRENT OR PROGRESSIVE PRIMARY BRAIN TUMORS</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Celgene</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Celgene</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will assess the efficacy, safety and tolerability of pomalidomide in children and&#xD;
      young adults aged 1 to &lt; 21 years with recurrent or progressive primary brain tumors in one&#xD;
      of four primary brain tumor types: high-grade glioma (HGG), medulloblastoma, ependymoma and&#xD;
      diffuse intrinsic pontine glioma (DIPG).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study will consist of 4 parallel groups of participants, one for each of the following&#xD;
      primary brain tumor types: high-grade glioma, medulloblastoma, ependymoma and DIPG. A Simon's&#xD;
      Optimal two-stage study design will be applied to each group and enrollment will occur as&#xD;
      follows:&#xD;
&#xD;
        -  Stage 1: Nine participants will be enrolled in each brain tumor type group&#xD;
&#xD;
        -  Stage 2: If during Stage 1, ≥ 2 participants achieves either an objective response&#xD;
           (either complete response or partial response) within the first 6 cycles of treatment&#xD;
           (or within the first 3 cycles for DIPG participants), or a long-term stable disease, an&#xD;
           additional 11 participants shall be enrolled; otherwise no additional participants will&#xD;
           be enrolled into that group.&#xD;
&#xD;
        -  If a total of 5 or more participants across all 20 participants in a given group (Stage&#xD;
           1 and 2) evaluable for the primary endpoint are observed as having either an objective&#xD;
           response (either complete response or partial response) within the first 6 cycles of&#xD;
           treatment (or within the first 3 cycles for DIPG participants) or a long-term stable&#xD;
           disease, pomalidomide will be considered effective in that disease indication.&#xD;
&#xD;
      Once treatment has been discontinued, participants will be followed up for up to 5 years from&#xD;
      enrollment of the last participant.&#xD;
&#xD;
      Participants who withdraw from either stage for reasons other than disease progression prior&#xD;
      to completing Cycle 1 of study treatment will be replaced.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">August 22, 2017</start_date>
  <completion_date type="Anticipated">September 27, 2023</completion_date>
  <primary_completion_date type="Actual">November 23, 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>Yes</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants With an Objective Response or Long-term Stable Disease</measure>
    <time_frame>6 months (first 6 cycles) or 3 months (first 3 cycles) for participants in the DIPG group</time_frame>
    <description>Objective response and long-term stable disease rate was defined as the percentage of participants who achieved either an objective response, defined as a complete response (CR) or partial response (PR) in the first 6 cycles of treatment (or within 3 cycles for DIPG), or long-term stable disease (SD) defined as SD maintained for ≥ 6 cycles (≥ 3 cycles for DIPG), measured from first dose date. Disease assessments were based on magnetic resonance imaging (MRI) assessed by an independent central review. CR: Disappearance of all lesions and no new lesions. PR: A reduction of ≥ 50% in the size of measurable lesions compared to baseline, and/or persistence of non-target lesions with no progression or decrease in size. SD: A decrease of &lt; 50% or an increase of &lt; 25% in the size of measurable lesions and no evidence of new lesions, response does not meet the criteria for CR, PR, or progressive disease, and/or the persistence of non-target lesions with no progression or decrease in size.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Who Achieved an Objective Response</measure>
    <time_frame>6 months (first 6 cycles) or 3 months (first 3 cycles) for participants in the DIPG group</time_frame>
    <description>Objective response rate was defined as the percentage of participants who achieved a complete response (CR) or partial response (PR) within the first 6 cycles of treatment (or within 3 cycles for participants in the DIPG group). Disease assessments were based on MRI and assessed by an independent central review. CR: Disappearance of all lesions and no new lesions. PR: A reduction of ≥ 50% in the size of measurable lesions compared to baseline, and/or the persistence of non-target lesions with no progression or decrease in size.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Long-term Stable Disease</measure>
    <time_frame>6 months (first 6 cycles) or 3 months (first 3 cycles) for participants in the DIPG group</time_frame>
    <description>Long-term stable disease (SD) rate was defined as the percentage of participants who achieved SD maintained for ≥ 6 cycles (or &gt; 3 cycles for DIPG), measured from the date of first dose of treatment. Disease assessments were based on MRI and assessed by an independent central review. SD: A decrease of &lt; 50% or an increase of &lt; 25% in the size of measurable lesions and no evidence of new lesions, response does not meet the criteria for CR, PR, or progressive disease, and/or the persistence of non-target lesions with no progression or decrease in size.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Kaplan-Meier Estimate of Duration of Response</measure>
    <time_frame>From the first dose of pomalidomide to the data cut-off date of 15 March 2019; median overall time on follow-up was 4.86 months (3.78, 5.65, 4.04, and 8.38 months in each group respectively).</time_frame>
    <description>Duration of response is defined as the time from the date of the first objective response (complete response or partial response) to disease progression, for participants with a response. Participants who did not have disease progression or had not died were censored at the time of their last disease assessment or at the time of start of new anticancer therapy, whichever occurred first. Progressive disease (PD): ≥ 25% increase in the size of the measurable lesions taking as a reference the smallest disease measurement recorded since the start of protocol therapy (nadir), or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions, or if spine MRI and/or lumbar cerebrospinal fluid (CSF) cytology were previously negative and became positive.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Kaplan-Meier Estimate of Progression-Free Survival (PFS)</measure>
    <time_frame>From the first dose of pomalidomide to the data cut-off date of 15 March 2019; median overall time on follow-up was 4.86 months (3.78, 5.65, 4.04, and 8.38 months in each group respectively).</time_frame>
    <description>Progression-free survival was defined as the time from the date of first dose of pomalidomide until the date progressive disease (PD) was first observed or until the date of death due to any cause, whichever occurred first. Participants who did not have PD or had not died at the time of analysis were censored at the time of their last disease assessment or at the start of new anticancer therapy, whichever occurred first. Progressive Disease (PD): ≥ 25% increase in the size of the measurable lesions taking as a reference the smallest disease measurement recorded since the start of protocol therapy (nadir), or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions, or if spine MRI and/or lumbar CSF cytology were previously negative and became positive.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Kalan-Meier Estimate of Overall Survival</measure>
    <time_frame>From the first dose of pomalidomide to the data cut-off date of 15 March 2019; median overall time on follow-up was 4.86 months (3.78, 5.65, 4.04, and 8.38 months in each group respectively).</time_frame>
    <description>Overall survival was defined as the time from the date of the first dose to the date of death (any cause). Participants who were alive were censored at the last known time that the participant was alive.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment-Emergent Adverse Events (TEAEs)</measure>
    <time_frame>From first dose of pomalidomide until 28 days after the last dose; median treatment duration was 84 days in the DIPG group, 112.0 days in the ependymoma group, 40.5 days in the high-grade glioma group and 57.0 days in the medulloblastoma group.</time_frame>
    <description>Treatment-emergent adverse events were defined as any adverse events (AE) occurring from the first dose of pomalidomide until 28 days after the last dose. The severity of each AE was graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03 and according to the following scale: Grade 1: Mild (transient or mild discomfort; no limitation in activity or medical intervention required); Grade 2: Moderate (mild to moderate limitation in activity, assistance may be needed; minimal medical intervention required); Grade 3: Severe (marked limitation in activity, assistance and medical intervention required, hospitalization possible); Grade 4: Life-threatening (extreme limitation in activity, significant assistance or medical intervention required, hospitalization or hospice care probable); Grade 5: Death. Drug-related AEs are those suspected by the Investigator as being related to administration of study drug.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">53</enrollment>
  <condition>Central Nervous System Neoplasms</condition>
  <condition>Medulloblastoma</condition>
  <arm_group>
    <arm_group_label>Pomalidomide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pomalidomide will administered at a starting dose of 2.6 m2/day. Pomalidomide will be provided as either a capsule (0.5 mg, 1 mg, 2 mg, 3 mg or 4 mg) or as an oral suspension (2 mg/mL).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pomalidomide</intervention_name>
    <description>: Subjects will be administered pomalidomide on Days 1 to 21, followed by a 7-day rest period, of each 28-day treatment cycle and will continue treatment for up to 24 cycles or until disease progression, withdrawal of consent/assent or unresolved toxicities as described in the protocol.</description>
    <arm_group_label>Pomalidomide</arm_group_label>
    <other_name>CC-4047</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pomalidomide</intervention_name>
    <description>Pomalidomide will be provided as gelatin capsules and as an oral suspension. The starting dose will be 2.6 mg/m²/day, administered on Days 1 to 21, followed by a 7-day rest period, of each 28-day treatment cycle.</description>
    <arm_group_label>Pomalidomide</arm_group_label>
    <other_name>CC-4047</other_name>
    <other_name>Pomalyst®</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subject is 1 to &lt; 21 years of age at the time of signing the Informed Consent&#xD;
             Form/Informed Assent Form (ICF/IAF).&#xD;
&#xD;
          2. Subject (when applicable, parental/legal representative) must understand and&#xD;
             voluntarily sign an ICF/IAF prior to any study-related assessments/procedures being&#xD;
             conducted.&#xD;
&#xD;
          3. Subject has received at least one prior standard therapy (or generally accepted&#xD;
             upfront therapy if no standard exists) and have no known curative therapy.&#xD;
&#xD;
          4. Subject has a diagnosis of high-grade glioma, medulloblastoma, ependymoma or diffuse&#xD;
             intrinsic pontine glioma (DIPG) that is recurrent or progressive. Subjects with&#xD;
             neurofibromatosis type 1 (NF-1) associated tumors are eligible if they meet all other&#xD;
             eligibility criteria.&#xD;
&#xD;
          5. Subject has histological verification of tumor either at the time of diagnosis or&#xD;
             recurrence. Subjects with DIPG are exempt from histologic verification if they have&#xD;
             typical magnetic resonance imaging (MRI) findings of DIPG&#xD;
&#xD;
          6. Subject has measurable disease defined as a tumor that is measurable in 2&#xD;
             perpendicular diameters on MRI. For a lesion to be considered measurable, it must be&#xD;
             at least twice the slice thickness on MRI (ie, visible on 2 or more axial slices)&#xD;
&#xD;
          7. To document the degree of tumor at study baseline, the following scan(s) must be&#xD;
             obtained:&#xD;
&#xD;
               -  A brain MRI with and without contrast (ie, gadolinium) and a spine MRI with&#xD;
                  contrast within 21 days prior to first dose of study treatment. For subjects on&#xD;
                  steroids, baseline MRI scans must be performed while on stable or decreasing dose&#xD;
                  of steroids for at least 5 days.&#xD;
&#xD;
          8. Subject has Karnofsky (age ≥ 16 years) or Lansky (age &lt; 16 years) performance status&#xD;
             score ≥ 50 at screening&#xD;
&#xD;
          9. Subject has adequate bone marrow function defined as:&#xD;
&#xD;
               -  Peripheral absolute neutrophil count (ANC) ≥ 1000/mm³&#xD;
&#xD;
               -  Platelet count ≥ 100,000/mm³ (transfusion independent defined as no platelet&#xD;
                  transfusion within 7 days and recovery from nadir)&#xD;
&#xD;
               -  Hemoglobin ≥ 8 g/dL (red blood cell [RBC] transfusion is allowed)&#xD;
&#xD;
         10. Subject has adequate renal function defined as:&#xD;
&#xD;
               -  Serum creatinine based on age/gender calculated using the Schwartz formula, or a&#xD;
                  24-hour creatinine clearance or radioisotope glomerular filtration rate (GFR)&#xD;
                  (radioisotope or iothalamate) ≥ 70 mL/min/1.73 m².&#xD;
&#xD;
         11. Subject has adequate liver function defined as:&#xD;
&#xD;
               -  Total bilirubin ≤ 1.5 X upper limit of normal (ULN) for current age (≤ 3 X ULN if&#xD;
                  increase in bilirubin is attributable to Gilbert's Syndrome)&#xD;
&#xD;
               -  Alanine aminotransferase (ALT) (SPGT) is ≤ 3 X ULN for age&#xD;
&#xD;
               -  Serum albumin ≥ 3 g/dL&#xD;
&#xD;
         12. Subject has adequate pulmonary function defined as:&#xD;
&#xD;
               -  No evidence of dyspnea at rest&#xD;
&#xD;
               -  A pulse oximetry ≥ 93%&#xD;
&#xD;
         13. Subject has recovered from clinically significant acute treatment related toxicities&#xD;
             from all prior therapies. Recovery is defined as a toxicity Grade ≤ 2 (common&#xD;
             terminology criteria for adverse events [CTCAE] v. 4.03).&#xD;
&#xD;
         14. Subject has no significant worsening in clinical status for a minimum of 7 days prior&#xD;
             to first dose of study drug.&#xD;
&#xD;
         15. Subject (and when applicable, with parental/legal representative) is willing and able&#xD;
             to adhere to the study visit schedule and other protocol requirements.&#xD;
&#xD;
         16. Females of Childbearing Potential (FCBP) and male subjects who have reached puberty&#xD;
             (and when applicable, with parental/legal representative) must agree to undergo&#xD;
             physician-approved reproductive education and discuss the side effects of the study&#xD;
             therapy on reproduction.&#xD;
&#xD;
         17. Females of childbearing potential must agree and meet the following conditions below:&#xD;
&#xD;
               -  Medically supervised (ie, performed in a clinic) pregnancy testing, including&#xD;
                  those who commit to true abstinence. Two pregnancy tests must be conducted prior&#xD;
                  to starting pomalidomide. The first pregnancy test must be performed 10 to 14&#xD;
                  days prior to the start of pomalidomide and the second pregnancy test must be&#xD;
                  performed within 24 hours prior to starting pomalidomide. Females of childbearing&#xD;
                  potential with regular or no menstrual cycles must also agree to have pregnancy&#xD;
                  tests weekly for the first 28 days study participation, every 28 days while on&#xD;
                  study, at study treatment discontinuation, and at Day 28 following pomalidomide&#xD;
                  discontinuation. If menstrual cycles are irregular, the pregnancy testing must&#xD;
                  occur weekly for the first 28 days of study participation and then every 14 days&#xD;
                  while on study, at study treatment discontinuation visit, and at Days 14 and 28&#xD;
                  following pomalidomide discontinuation.&#xD;
&#xD;
               -  Female subjects must, as appropriate to age and at the discretion of the study&#xD;
                  Investigator, either commit to true abstinence from heterosexual contact and/or&#xD;
                  agree to the use of two reliable forms of approved and effective contraceptive&#xD;
                  methods simultaneously. The two methods of reliable contraception must include&#xD;
                  one highly effective method (ie, oral, injectable, or implantable hormonal&#xD;
                  contraceptive; tubal ligation; intra-uterine device; vasectomized partner) and&#xD;
                  one additional effective barrier method (ie, male condom, diaphragm, cervical&#xD;
                  cap) 28 days prior to starting pomalidomide, throughout the entire duration of&#xD;
                  study treatment including dose interruptions and 28 days after discontinuation of&#xD;
                  pomalidomide.&#xD;
&#xD;
               -  All male and female subjects must follow all requirements defined in the&#xD;
                  pomalidomide Pregnancy Prevention Program.&#xD;
&#xD;
         18. Male subjects must, as appropriate to age and the discretion of the study physician:&#xD;
&#xD;
               -  Practice true abstinence or agree to use a condom during sexual contact with a&#xD;
                  pregnant female or a female of child bearing potential while participating in the&#xD;
                  study, during dose interruptions and for at least 28 days following pomalidomide&#xD;
                  discontinuation, even if he has undergone a successful vasectomy or practices&#xD;
                  complete abstinence.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subject has a history of non-central line related thrombosis (arterial or venous),&#xD;
             more than one prior central-line related thrombosis or known coagulopathy.&#xD;
&#xD;
          2. Subject has first degree family member with a known hereditary coagulopathy.&#xD;
&#xD;
          3. Subject is actively on anticoagulation therapy.&#xD;
&#xD;
          4. Subject has had major (per Investigator discretion) surgery, with the exception of&#xD;
             tumor resection, within 21 days from first dose of study drug.&#xD;
&#xD;
          5. Subject has previously received (presence of any of the following will exclude a&#xD;
             subject from enrollment):&#xD;
&#xD;
               -  Any prior treatment with pomalidomide. Subjects who have prior treatment with&#xD;
                  other immunomodulatory compounds (thalidomide, lenalidomide) are eligible if they&#xD;
                  meet all other eligibility criteria and did not have allergic reactions or other&#xD;
                  &quot;significant toxicity&quot; per Investigator discretion associated with lenalidomide&#xD;
                  or thalidomide use.&#xD;
&#xD;
               -  Myelosuppressive chemotherapy, immunotherapy, or any investigational agent: ≤ 21&#xD;
                  days (≤ 42 days if a nitrosourea) prior to screening.&#xD;
&#xD;
               -  Biological (anti-neoplastic) therapy: ≤ 7 days prior to screening.&#xD;
&#xD;
               -  Immunomodulatory therapy: ≤ 28 days prior to screening.&#xD;
&#xD;
               -  Monoclonal antibody treatment and agents with known prolonged half-lives: &lt; 3&#xD;
                  halflives have elapsed or ≤ 28 days prior to screening, whichever is longer.&#xD;
&#xD;
               -  Prior radiation:&#xD;
&#xD;
                    -  Cranial irradiation, total body irradiation (TBI), or ≥ 50% radiation of&#xD;
                       pelvis ≤ 3 months prior to screening.&#xD;
&#xD;
                    -  Focal irradiation: ≤ 3 weeks prior to screening if radiation field involved&#xD;
                       a nontarget lesion; ≤ 6 weeks prior to screening if radiation field involved&#xD;
                       a target lesion.&#xD;
&#xD;
             Note: True disease progression following prior irradiation therapy must be confirmed&#xD;
             by Investigator prior to screening.&#xD;
&#xD;
               -  Bone marrow transplant:&#xD;
&#xD;
                    -  Presence of graft versus host disease (GVHD).&#xD;
&#xD;
                    -  &lt; 6 months since allogeneic bone marrow transplant prior to screening.&#xD;
&#xD;
                    -  &lt; 3 months since autologous bone marrow/stem cell transplant prior to&#xD;
                       screening.&#xD;
&#xD;
                    -  &lt; 3 months since stem cell transplant (SCT) or Rescue without TBI with no&#xD;
                       evidence of GVHD prior to screening.&#xD;
&#xD;
               -  Radioisotopes: fluorothymidine (18FLT) ≤ 72 hours prior to first dose of study&#xD;
                  drug&#xD;
&#xD;
          6. Subject has received therapy with a known moderate to potent CYP1A2 inhibitor within&#xD;
             14 days or 5 half-lives of first dose of study treatment (whichever is longer).&#xD;
&#xD;
          7. Subject has received colony-stimulating growth factor(s) within 7 days prior to&#xD;
             screening (or within 14 days if subject received polyethylene glycol formulations).&#xD;
&#xD;
          8. Subject is pregnant, breast-feeding or lactating.&#xD;
&#xD;
          9. Subject has an untreated or uncontrolled infection defined as ongoing signs/symptoms&#xD;
             related to the infection without improvement despite appropriate antibiotics,&#xD;
             antiviral therapy and/or other treatment.&#xD;
&#xD;
         10. Subject has active infectious hepatitis, type A, B, or C, or chronic carriers of&#xD;
             hepatitis C.&#xD;
&#xD;
         11. Subject has any prior history of malignancies, other than high-grade glioma,&#xD;
             medulloblastoma, ependymoma or DIPG (Note: radiation-associated gliomas are excluded&#xD;
             from enrollment)&#xD;
&#xD;
         12. Subject who, in the opinion of the Investigator, has any significant medical&#xD;
             condition, laboratory abnormality, or psychiatric illness that would prevent the&#xD;
             subject from participating in the study.&#xD;
&#xD;
         13. Subject has any condition including the presence of laboratory abnormalities which, in&#xD;
             the opinion of the Investigator, places the subject at unacceptable risk if he/she&#xD;
             were to participate in the study.&#xD;
&#xD;
         14. Subject has any condition that confounds the ability to interpret data from the study.&#xD;
&#xD;
         15. Subject has symptomatic cardiac disorders (CTCAE v. 4.03 Grade 3 and 4).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>21 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bristol-Myers Squibb</last_name>
    <role>Study Director</role>
    <affiliation>Bristol-Myers Squibb</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Stanford University Cancer Center</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305-5750</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Of Florida</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ann and Robert H Lurie Childrens Hospital of Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 506</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Children's Hospital</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 104</name>
      <address>
        <city>Lille</city>
        <state>Nord</state>
        <zip>59020</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 102</name>
      <address>
        <city>Lyon</city>
        <zip>69008</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 103</name>
      <address>
        <city>Marseille Cedex 01</city>
        <zip>13005</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 100</name>
      <address>
        <city>Paris</city>
        <zip>75005</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 106</name>
      <address>
        <city>Toulouse</city>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 105</name>
      <address>
        <city>Vandoeuvre les Nancy</city>
        <zip>54511</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 101</name>
      <address>
        <city>Villejuif CEDEX</city>
        <zip>94805</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 201</name>
      <address>
        <city>Genova</city>
        <zip>0</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 200</name>
      <address>
        <city>Milan</city>
        <zip>20133</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 202</name>
      <address>
        <city>Roma</city>
        <zip>00165</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 302</name>
      <address>
        <city>Barcelona</city>
        <zip>8035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 300</name>
      <address>
        <city>Madrid</city>
        <zip>28009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 301</name>
      <address>
        <city>Valencia</city>
        <zip>46026</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 400</name>
      <address>
        <city>Leeds</city>
        <zip>LS7 4SA</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 403</name>
      <address>
        <city>London</city>
        <zip>WC1N 3JH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Local Institution - 401</name>
      <address>
        <city>Sutton-Surrey</city>
        <zip>SM2 5PT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
    <country>Italy</country>
    <country>Spain</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html</url>
    <description>BMS Clinical Trial Information</description>
  </link>
  <link>
    <url>https://www.bmsstudyconnect.com/s/US/English/USenHome</url>
    <description>BMS Clinical Trial Patient Recruiting</description>
  </link>
  <link>
    <url>https://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm</url>
    <description>FDA Safety Alerts and Recalls</description>
  </link>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>August 18, 2017</study_first_submitted>
  <study_first_submitted_qc>August 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 22, 2017</study_first_posted>
  <results_first_submitted>November 22, 2019</results_first_submitted>
  <results_first_submitted_qc>November 22, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">December 10, 2019</results_first_posted>
  <last_update_submitted>March 6, 2023</last_update_submitted>
  <last_update_submitted_qc>March 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Pediatric</keyword>
  <keyword>Brain Tumor</keyword>
  <keyword>Central Nervous System Neoplasms</keyword>
  <keyword>Glioma</keyword>
  <keyword>High-grade glioma</keyword>
  <keyword>HGG</keyword>
  <keyword>Ependymoma</keyword>
  <keyword>Medulloblastoma</keyword>
  <keyword>DIPG</keyword>
  <keyword>Diffuse intrinsic pontine gliomaProgressive</keyword>
  <keyword>RecurrentPomalidomide</keyword>
  <keyword>PomalystImnovid</keyword>
  <keyword>CC-4047</keyword>
  <keyword>Children</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Neoplasms</mesh_term>
    <mesh_term>Medulloblastoma</mesh_term>
    <mesh_term>Nervous System Neoplasms</mesh_term>
    <mesh_term>Central Nervous System Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thalidomide</mesh_term>
    <mesh_term>Pomalidomide</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>December 20, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/31/NCT03257631/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 20, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/31/NCT03257631/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were enrolled at 18 sites in France, Italy, Spain, UK, and the USA. The study consisted of 4 groups, for each of the following primary brain tumor types: diffuse intrinsic pontine glioma (DIPG), ependymoma, high-grade glioma, and medulloblastoma. The study is currently ongoing; results are reported as of 15 March 2019 data cutoff date.</recruitment_details>
      <pre_assignment_details>In stage 1 approximately 9 participants were to be enrolled in parallel to each group. If two or more participants in a group achieved an objective response or long-term stable disease within the first 6 cycles of treatment (within the first 3 cycles for DIPG) an additional 11 participants were to be enrolled in that group.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Diffuse Intrinsic Pontine Glioma</title>
          <description>Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.</description>
        </group>
        <group group_id="P2">
          <title>Ependymoma</title>
          <description>Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.</description>
        </group>
        <group group_id="P3">
          <title>High-grade Glioma</title>
          <description>Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.</description>
        </group>
        <group group_id="P4">
          <title>Medulloblastoma</title>
          <description>Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="9"/>
                <participants group_id="P3" count="23"/>
                <participants group_id="P4" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received Study Drug</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="9"/>
                <participants group_id="P3" count="22"/>
                <participants group_id="P4" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="9"/>
                <participants group_id="P3" count="23"/>
                <participants group_id="P4" count="10"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="13"/>
                <participants group_id="P4" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Progressive Disease</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Parent/Guardian</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="4"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Still on Study</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="4"/>
                <participants group_id="P4" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The intent-to-treat population includes all enrolled participants, regardless of whether they received any treatment or not.</population>
      <group_list>
        <group group_id="B1">
          <title>Diffuse Intrinsic Pontine Glioma</title>
          <description>Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.</description>
        </group>
        <group group_id="B2">
          <title>Ependymoma</title>
          <description>Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.</description>
        </group>
        <group group_id="B3">
          <title>High-grade Glioma</title>
          <description>Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.</description>
        </group>
        <group group_id="B4">
          <title>Medulloblastoma</title>
          <description>Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.</description>
        </group>
        <group group_id="B5">
          <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="11"/>
            <count group_id="B2" value="9"/>
            <count group_id="B3" value="23"/>
            <count group_id="B4" value="10"/>
            <count group_id="B5" value="53"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7.0" lower_limit="4" upper_limit="12"/>
                    <measurement group_id="B2" value="12.0" lower_limit="4" upper_limit="15"/>
                    <measurement group_id="B3" value="14.0" lower_limit="5" upper_limit="18"/>
                    <measurement group_id="B4" value="10.0" lower_limit="4" upper_limit="17"/>
                    <measurement group_id="B5" value="12.0" lower_limit="4" upper_limit="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>≥ 1 to &lt; 6 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>≥ 6 to &lt; 12 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>≥ 12 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="17"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="27"/>
                  </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="4"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="15"/>
                    <measurement group_id="B4" value="7"/>
                    <measurement group_id="B5" value="34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="13"/>
                    <measurement group_id="B4" value="8"/>
                    <measurement group_id="B5" value="37"/>
                  </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="4"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="5"/>
                  </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>
              <category_list>
                <category>
                  <title>American Indian or Alaskan Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="11"/>
                    <measurement group_id="B4" value="8"/>
                    <measurement group_id="B5" value="38"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Collected or Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Other</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants With an Objective Response or Long-term Stable Disease</title>
        <description>Objective response and long-term stable disease rate was defined as the percentage of participants who achieved either an objective response, defined as a complete response (CR) or partial response (PR) in the first 6 cycles of treatment (or within 3 cycles for DIPG), or long-term stable disease (SD) defined as SD maintained for ≥ 6 cycles (≥ 3 cycles for DIPG), measured from first dose date. Disease assessments were based on magnetic resonance imaging (MRI) assessed by an independent central review. CR: Disappearance of all lesions and no new lesions. PR: A reduction of ≥ 50% in the size of measurable lesions compared to baseline, and/or persistence of non-target lesions with no progression or decrease in size. SD: A decrease of &lt; 50% or an increase of &lt; 25% in the size of measurable lesions and no evidence of new lesions, response does not meet the criteria for CR, PR, or progressive disease, and/or the persistence of non-target lesions with no progression or decrease in size.</description>
        <time_frame>6 months (first 6 cycles) or 3 months (first 3 cycles) for participants in the DIPG group</time_frame>
        <population>The response population consisted of all participants enrolled who met eligibility criteria relevant to efficacy, and received at least one cycle of pomalidomide if therapy was not discontinued earlier due to progressive disease (PD).</population>
        <group_list>
          <group group_id="O1">
            <title>Diffuse Intrinsic Pontine Glioma</title>
            <description>Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.</description>
          </group>
          <group group_id="O2">
            <title>Ependymoma</title>
            <description>Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.</description>
          </group>
          <group group_id="O3">
            <title>High-grade Glioma</title>
            <description>Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.</description>
          </group>
          <group group_id="O4">
            <title>Medulloblastoma</title>
            <description>Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With an Objective Response or Long-term Stable Disease</title>
          <description>Objective response and long-term stable disease rate was defined as the percentage of participants who achieved either an objective response, defined as a complete response (CR) or partial response (PR) in the first 6 cycles of treatment (or within 3 cycles for DIPG), or long-term stable disease (SD) defined as SD maintained for ≥ 6 cycles (≥ 3 cycles for DIPG), measured from first dose date. Disease assessments were based on magnetic resonance imaging (MRI) assessed by an independent central review. CR: Disappearance of all lesions and no new lesions. PR: A reduction of ≥ 50% in the size of measurable lesions compared to baseline, and/or persistence of non-target lesions with no progression or decrease in size. SD: A decrease of &lt; 50% or an increase of &lt; 25% in the size of measurable lesions and no evidence of new lesions, response does not meet the criteria for CR, PR, or progressive disease, and/or the persistence of non-target lesions with no progression or decrease in size.</description>
          <population>The response population consisted of all participants enrolled who met eligibility criteria relevant to efficacy, and received at least one cycle of pomalidomide if therapy was not discontinued earlier due to progressive disease (PD).</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="9"/>
                <count group_id="O3" value="19"/>
                <count group_id="O4" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0.0" upper_limit="33.6"/>
                    <measurement group_id="O2" value="11.1" lower_limit="0.3" upper_limit="48.2"/>
                    <measurement group_id="O3" value="10.5" lower_limit="1.3" upper_limit="33.1"/>
                    <measurement group_id="O4" value="0" lower_limit="0.0" upper_limit="33.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Who Achieved an Objective Response</title>
        <description>Objective response rate was defined as the percentage of participants who achieved a complete response (CR) or partial response (PR) within the first 6 cycles of treatment (or within 3 cycles for participants in the DIPG group). Disease assessments were based on MRI and assessed by an independent central review. CR: Disappearance of all lesions and no new lesions. PR: A reduction of ≥ 50% in the size of measurable lesions compared to baseline, and/or the persistence of non-target lesions with no progression or decrease in size.</description>
        <time_frame>6 months (first 6 cycles) or 3 months (first 3 cycles) for participants in the DIPG group</time_frame>
        <population>Response population</population>
        <group_list>
          <group group_id="O1">
            <title>Diffuse Intrinsic Pontine Glioma</title>
            <description>Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.</description>
          </group>
          <group group_id="O2">
            <title>Ependymoma</title>
            <description>Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.</description>
          </group>
          <group group_id="O3">
            <title>High-grade Glioma</title>
            <description>Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.</description>
          </group>
          <group group_id="O4">
            <title>Medulloblastoma</title>
            <description>Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Who Achieved an Objective Response</title>
          <description>Objective response rate was defined as the percentage of participants who achieved a complete response (CR) or partial response (PR) within the first 6 cycles of treatment (or within 3 cycles for participants in the DIPG group). Disease assessments were based on MRI and assessed by an independent central review. CR: Disappearance of all lesions and no new lesions. PR: A reduction of ≥ 50% in the size of measurable lesions compared to baseline, and/or the persistence of non-target lesions with no progression or decrease in size.</description>
          <population>Response population</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="9"/>
                <count group_id="O3" value="19"/>
                <count group_id="O4" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0.0" upper_limit="33.6"/>
                    <measurement group_id="O2" value="0" lower_limit="0.0" upper_limit="33.6"/>
                    <measurement group_id="O3" value="5.3" lower_limit="0.1" upper_limit="26.0"/>
                    <measurement group_id="O4" value="0" lower_limit="0.0" upper_limit="33.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Long-term Stable Disease</title>
        <description>Long-term stable disease (SD) rate was defined as the percentage of participants who achieved SD maintained for ≥ 6 cycles (or &gt; 3 cycles for DIPG), measured from the date of first dose of treatment. Disease assessments were based on MRI and assessed by an independent central review. SD: A decrease of &lt; 50% or an increase of &lt; 25% in the size of measurable lesions and no evidence of new lesions, response does not meet the criteria for CR, PR, or progressive disease, and/or the persistence of non-target lesions with no progression or decrease in size.</description>
        <time_frame>6 months (first 6 cycles) or 3 months (first 3 cycles) for participants in the DIPG group</time_frame>
        <population>Response population</population>
        <group_list>
          <group group_id="O1">
            <title>Diffuse Intrinsic Pontine Glioma</title>
            <description>Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.</description>
          </group>
          <group group_id="O2">
            <title>Ependymoma</title>
            <description>Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.</description>
          </group>
          <group group_id="O3">
            <title>High-grade Glioma</title>
            <description>Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.</description>
          </group>
          <group group_id="O4">
            <title>Medulloblastoma</title>
            <description>Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Long-term Stable Disease</title>
          <description>Long-term stable disease (SD) rate was defined as the percentage of participants who achieved SD maintained for ≥ 6 cycles (or &gt; 3 cycles for DIPG), measured from the date of first dose of treatment. Disease assessments were based on MRI and assessed by an independent central review. SD: A decrease of &lt; 50% or an increase of &lt; 25% in the size of measurable lesions and no evidence of new lesions, response does not meet the criteria for CR, PR, or progressive disease, and/or the persistence of non-target lesions with no progression or decrease in size.</description>
          <population>Response population</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="9"/>
                <count group_id="O3" value="19"/>
                <count group_id="O4" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0.0" upper_limit="33.6"/>
                    <measurement group_id="O2" value="11.1" lower_limit="0.3" upper_limit="48.2"/>
                    <measurement group_id="O3" value="5.3" lower_limit="0.1" upper_limit="26.0"/>
                    <measurement group_id="O4" value="0" lower_limit="0.0" upper_limit="33.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Kaplan-Meier Estimate of Duration of Response</title>
        <description>Duration of response is defined as the time from the date of the first objective response (complete response or partial response) to disease progression, for participants with a response. Participants who did not have disease progression or had not died were censored at the time of their last disease assessment or at the time of start of new anticancer therapy, whichever occurred first. Progressive disease (PD): ≥ 25% increase in the size of the measurable lesions taking as a reference the smallest disease measurement recorded since the start of protocol therapy (nadir), or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions, or if spine MRI and/or lumbar cerebrospinal fluid (CSF) cytology were previously negative and became positive.</description>
        <time_frame>From the first dose of pomalidomide to the data cut-off date of 15 March 2019; median overall time on follow-up was 4.86 months (3.78, 5.65, 4.04, and 8.38 months in each group respectively).</time_frame>
        <population>Participants in the response population with an objective response</population>
        <group_list>
          <group group_id="O1">
            <title>Diffuse Intrinsic Pontine Glioma</title>
            <description>Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.</description>
          </group>
          <group group_id="O2">
            <title>Ependymoma</title>
            <description>Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.</description>
          </group>
          <group group_id="O3">
            <title>High-grade Glioma</title>
            <description>Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.</description>
          </group>
          <group group_id="O4">
            <title>Medulloblastoma</title>
            <description>Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.</description>
          </group>
        </group_list>
        <measure>
          <title>Kaplan-Meier Estimate of Duration of Response</title>
          <description>Duration of response is defined as the time from the date of the first objective response (complete response or partial response) to disease progression, for participants with a response. Participants who did not have disease progression or had not died were censored at the time of their last disease assessment or at the time of start of new anticancer therapy, whichever occurred first. Progressive disease (PD): ≥ 25% increase in the size of the measurable lesions taking as a reference the smallest disease measurement recorded since the start of protocol therapy (nadir), or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions, or if spine MRI and/or lumbar cerebrospinal fluid (CSF) cytology were previously negative and became positive.</description>
          <population>Participants in the response population with an objective response</population>
          <units>weeks</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="1"/>
                <count group_id="O4" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O3" value="NA" lower_limit="NA" upper_limit="NA">Could not be estimated due to the low number of participants with an event</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Kaplan-Meier Estimate of Progression-Free Survival (PFS)</title>
        <description>Progression-free survival was defined as the time from the date of first dose of pomalidomide until the date progressive disease (PD) was first observed or until the date of death due to any cause, whichever occurred first. Participants who did not have PD or had not died at the time of analysis were censored at the time of their last disease assessment or at the start of new anticancer therapy, whichever occurred first. Progressive Disease (PD): ≥ 25% increase in the size of the measurable lesions taking as a reference the smallest disease measurement recorded since the start of protocol therapy (nadir), or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions, or if spine MRI and/or lumbar CSF cytology were previously negative and became positive.</description>
        <time_frame>From the first dose of pomalidomide to the data cut-off date of 15 March 2019; median overall time on follow-up was 4.86 months (3.78, 5.65, 4.04, and 8.38 months in each group respectively).</time_frame>
        <population>Response population</population>
        <group_list>
          <group group_id="O1">
            <title>Diffuse Intrinsic Pontine Glioma</title>
            <description>Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.</description>
          </group>
          <group group_id="O2">
            <title>Ependymoma</title>
            <description>Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.</description>
          </group>
          <group group_id="O3">
            <title>High-grade Glioma</title>
            <description>Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.</description>
          </group>
          <group group_id="O4">
            <title>Medulloblastoma</title>
            <description>Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.</description>
          </group>
        </group_list>
        <measure>
          <title>Kaplan-Meier Estimate of Progression-Free Survival (PFS)</title>
          <description>Progression-free survival was defined as the time from the date of first dose of pomalidomide until the date progressive disease (PD) was first observed or until the date of death due to any cause, whichever occurred first. Participants who did not have PD or had not died at the time of analysis were censored at the time of their last disease assessment or at the start of new anticancer therapy, whichever occurred first. Progressive Disease (PD): ≥ 25% increase in the size of the measurable lesions taking as a reference the smallest disease measurement recorded since the start of protocol therapy (nadir), or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions, or if spine MRI and/or lumbar CSF cytology were previously negative and became positive.</description>
          <population>Response population</population>
          <units>weeks</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="9"/>
                <count group_id="O3" value="19"/>
                <count group_id="O4" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.29" lower_limit="2.86" upper_limit="12.57"/>
                    <measurement group_id="O2" value="8.43" lower_limit="5.57" upper_limit="16.14"/>
                    <measurement group_id="O3" value="7.86" lower_limit="5.14" upper_limit="8.14"/>
                    <measurement group_id="O4" value="8.43" lower_limit="7.29" upper_limit="18.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Kalan-Meier Estimate of Overall Survival</title>
        <description>Overall survival was defined as the time from the date of the first dose to the date of death (any cause). Participants who were alive were censored at the last known time that the participant was alive.</description>
        <time_frame>From the first dose of pomalidomide to the data cut-off date of 15 March 2019; median overall time on follow-up was 4.86 months (3.78, 5.65, 4.04, and 8.38 months in each group respectively).</time_frame>
        <population>Response population</population>
        <group_list>
          <group group_id="O1">
            <title>Diffuse Intrinsic Pontine Glioma</title>
            <description>Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.</description>
          </group>
          <group group_id="O2">
            <title>Ependymoma</title>
            <description>Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.</description>
          </group>
          <group group_id="O3">
            <title>High-grade Glioma</title>
            <description>Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.</description>
          </group>
          <group group_id="O4">
            <title>Medulloblastoma</title>
            <description>Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.</description>
          </group>
        </group_list>
        <measure>
          <title>Kalan-Meier Estimate of Overall Survival</title>
          <description>Overall survival was defined as the time from the date of the first dose to the date of death (any cause). Participants who were alive were censored at the last known time that the participant was alive.</description>
          <population>Response population</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="9"/>
                <count group_id="O3" value="19"/>
                <count group_id="O4" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.78" lower_limit="0.66" upper_limit="NA">Could not be estimated due to the low number of events</measurement>
                    <measurement group_id="O2" value="12.02" lower_limit="2.86" upper_limit="NA">Could not be estimated due to the low number of events</measurement>
                    <measurement group_id="O3" value="5.06" lower_limit="2.04" upper_limit="11.63"/>
                    <measurement group_id="O4" value="11.60" lower_limit="1.74" upper_limit="NA">Could not be estimated due to the low number of events</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Treatment-Emergent Adverse Events (TEAEs)</title>
        <description>Treatment-emergent adverse events were defined as any adverse events (AE) occurring from the first dose of pomalidomide until 28 days after the last dose. The severity of each AE was graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03 and according to the following scale: Grade 1: Mild (transient or mild discomfort; no limitation in activity or medical intervention required); Grade 2: Moderate (mild to moderate limitation in activity, assistance may be needed; minimal medical intervention required); Grade 3: Severe (marked limitation in activity, assistance and medical intervention required, hospitalization possible); Grade 4: Life-threatening (extreme limitation in activity, significant assistance or medical intervention required, hospitalization or hospice care probable); Grade 5: Death. Drug-related AEs are those suspected by the Investigator as being related to administration of study drug.</description>
        <time_frame>From first dose of pomalidomide until 28 days after the last dose; median treatment duration was 84 days in the DIPG group, 112.0 days in the ependymoma group, 40.5 days in the high-grade glioma group and 57.0 days in the medulloblastoma group.</time_frame>
        <population>The safety population included all participants who received at least 1 dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Diffuse Intrinsic Pontine Glioma</title>
            <description>Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.</description>
          </group>
          <group group_id="O2">
            <title>Ependymoma</title>
            <description>Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.</description>
          </group>
          <group group_id="O3">
            <title>High-grade Glioma</title>
            <description>Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.</description>
          </group>
          <group group_id="O4">
            <title>Medulloblastoma</title>
            <description>Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment-Emergent Adverse Events (TEAEs)</title>
          <description>Treatment-emergent adverse events were defined as any adverse events (AE) occurring from the first dose of pomalidomide until 28 days after the last dose. The severity of each AE was graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03 and according to the following scale: Grade 1: Mild (transient or mild discomfort; no limitation in activity or medical intervention required); Grade 2: Moderate (mild to moderate limitation in activity, assistance may be needed; minimal medical intervention required); Grade 3: Severe (marked limitation in activity, assistance and medical intervention required, hospitalization possible); Grade 4: Life-threatening (extreme limitation in activity, significant assistance or medical intervention required, hospitalization or hospice care probable); Grade 5: Death. Drug-related AEs are those suspected by the Investigator as being related to administration of study drug.</description>
          <population>The safety population included all participants who received at least 1 dose of study drug.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="9"/>
                <count group_id="O3" value="22"/>
                <count group_id="O4" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Any treatment-emergent adverse event (TEAE)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="8"/>
                    <measurement group_id="O3" value="21"/>
                    <measurement group_id="O4" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAE related to study drug</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="7"/>
                    <measurement group_id="O3" value="14"/>
                    <measurement group_id="O4" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="4"/>
                    <measurement group_id="O3" value="13"/>
                    <measurement group_id="O4" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious TEAE related to study drug</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="6"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 3/4 TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="6"/>
                    <measurement group_id="O3" value="14"/>
                    <measurement group_id="O4" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 3/4 TEAE related to study drug</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="10"/>
                    <measurement group_id="O4" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAE leading to death</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="3"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAE leading to dose reduction</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAE leading to dose interruption</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="5"/>
                    <measurement group_id="O4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAE leading to study drug discontinuation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>All-cause mortality is reported from enrollment to the data cut-off date of 15 March 2019; median overall time on follow-up was 4.86 months (3.78, 5.65, 4.04, and 8.38 months in each group respectively). Adverse events are reported from the first dose of study drug until 28 days after the last dose; median treatment duration was 84 days in the DIPG group, 112.0 days in the ependymoma group, 40.5 days in the high-grade glioma group and 57.0 days in the medulloblastoma group.</time_frame>
      <desc>All-cause mortality is reported for all enrolled participants, regardless of whether the participant received study treatment or not. Adverse events are reported for all participants who received at least 1 dose of pomalidomide.</desc>
      <group_list>
        <group group_id="E1">
          <title>Diffuse Intrinsic Pontine Glioma</title>
          <description>Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.</description>
        </group>
        <group group_id="E2">
          <title>Ependymoma</title>
          <description>Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.</description>
        </group>
        <group group_id="E3">
          <title>High-grade Glioma</title>
          <description>Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.</description>
        </group>
        <group group_id="E4">
          <title>Medulloblastoma</title>
          <description>Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>21.0</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="8" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="13" subjects_at_risk="23"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="13" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Vision blurred</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Gait disturbance</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>General physical health deterioration</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Anorectal infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Encephalitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Herpes zoster</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Mastoiditis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Respiratory syncytial virus bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Tumour haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Ataxia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Depressed level of consciousness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dyskinesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Generalised tonic-clonic seizure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hemiparesis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hydrocephalus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Intracranial pressure increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Monoplegia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Neurological decompensation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Transient ischaemic attack</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>21.0</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="11" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="20" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="9" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Lymphopenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Bradycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blindness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Conjunctival hyperaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Mydriasis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Enteritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Odynophagia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Salivary hypersecretion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Gait disturbance</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>General physical health deterioration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperbilirubinaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Device related infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Eye infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Fungal infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Laryngitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Molluscum contagiosum</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Oral candidiasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Otitis externa</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Parotitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Rhinitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Rhinovirus infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Ligament sprain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Upper limb fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Urine output decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Weight increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypercalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypernatraemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypoalbuminaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypocalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypomagnesaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypophosphataemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Temporomandibular joint syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Haemangioma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Aphasia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Ataxia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Depressed level of consciousness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hemiparesis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hydrocephalus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Muscle spasticity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Pyramidal tract syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>VIth nerve disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Confusional state</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Personality change</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Pollakiuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Urinary hesitation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Urinary incontinence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Urinary retention</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Bronchostenosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hiccups</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Pharyngeal erythema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Sleep apnoea syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Tonsillar inflammation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Decubitus ulcer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dermatitis acneiform</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Eczema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Palmar-plantar erythrodysaesthesia syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Pruritus generalised</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Rash pruritic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Urticaria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Flushing</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Pallor</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </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>Results from a center cannot be submitted for publication before results of multicenter study are published unless it is &gt; 1 year since study completion. Then, Investigator can publish if manuscript is submitted to Celgene 60 days prior to submission. If Celgene decides publication would hinder drug development, Investigator must delay submission for up to 90 additional days. Investigator must delete confidential information before submission and defer publication to permit patent applications.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Anne McClain</name_or_title>
      <organization>Celgene Corporation</organization>
      <phone>1-888-260-1599</phone>
      <email>clinicaltrialdisclosure@celgene.com</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/NCT03257631
org study id: CC-4047-BRN-001
secondary id: U1111-1199-3348
secondary id: 2016-002903-25
nct id: NCT03257631
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study will assess the efficacy, safety and tolerability of pomalidomide in children and
      young adults aged 1 to < 21 years with recurrent or progressive primary brain tumors in one
      of four primary brain tumor types: high-grade glioma (HGG), medulloblastoma, ependymoma and
      diffuse intrinsic pontine glioma (DIPG).
The study will consist of 4 parallel groups of participants, one for each of the following
      primary brain tumor types: high-grade glioma, medulloblastoma, ependymoma and DIPG. A Simon's
      Optimal two-stage study design will be applied to each group and enrollment will occur as
      follows:

        -  Stage 1: Nine participants will be enrolled in each brain tumor type group

        -  Stage 2: If during Stage 1, ≥ 2 participants achieves either an objective response
           (either complete response or partial response) within the first 6 cycles of treatment
           (or within the first 3 cycles for DIPG participants), or a long-term stable disease, an
           additional 11 participants shall be enrolled; otherwise no additional participants will
           be enrolled into that group.

        -  If a total of 5 or more participants across all 20 participants in a given group (Stage
           1 and 2) evaluable for the primary endpoint are observed as having either an objective
           response (either complete response or partial response) within the first 6 cycles of
           treatment (or within the first 3 cycles for DIPG participants) or a long-term stable
           disease, pomalidomide will be considered effective in that disease indication.

      Once treatment has been discontinued, participants will be followed up for up to 5 years from
      enrollment of the last participant.

      Participants who withdraw from either stage for reasons other than disease progression prior
      to completing Cycle 1 of study treatment will be replaced.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Participants With an Objective Response or Long-term Stable Disease
time frame: 6 months (first 6 cycles) or 3 months (first 3 cycles) for participants in the DIPG group
description: Objective response and long-term stable disease rate was defined as the percentage of participants who achieved either an objective response, defined as a complete response (CR) or partial response (PR) in the first 6 cycles of treatment (or within 3 cycles for DIPG), or long-term stable disease (SD) defined as SD maintained for ≥ 6 cycles (≥ 3 cycles for DIPG), measured from first dose date. Disease assessments were based on magnetic resonance imaging (MRI) assessed by an independent central review. CR: Disappearance of all lesions and no new lesions. PR: A reduction of ≥ 50% in the size of measurable lesions compared to baseline, and/or persistence of non-target lesions with no progression or decrease in size. SD: A decrease of < 50% or an increase of < 25% in the size of measurable lesions and no evidence of new lesions, response does not meet the criteria for CR, PR, or progressive disease, and/or the persistence of non-target lesions with no progression or decrease in size.
measure: Percentage of Participants Who Achieved an Objective Response
time frame: 6 months (first 6 cycles) or 3 months (first 3 cycles) for participants in the DIPG group
description: Objective response rate was defined as the percentage of participants who achieved a complete response (CR) or partial response (PR) within the first 6 cycles of treatment (or within 3 cycles for participants in the DIPG group). Disease assessments were based on MRI and assessed by an independent central review. CR: Disappearance of all lesions and no new lesions. PR: A reduction of ≥ 50% in the size of measurable lesions compared to baseline, and/or the persistence of non-target lesions with no progression or decrease in size.
measure: Percentage of Participants With Long-term Stable Disease
time frame: 6 months (first 6 cycles) or 3 months (first 3 cycles) for participants in the DIPG group
description: Long-term stable disease (SD) rate was defined as the percentage of participants who achieved SD maintained for ≥ 6 cycles (or > 3 cycles for DIPG), measured from the date of first dose of treatment. Disease assessments were based on MRI and assessed by an independent central review. SD: A decrease of < 50% or an increase of < 25% in the size of measurable lesions and no evidence of new lesions, response does not meet the criteria for CR, PR, or progressive disease, and/or the persistence of non-target lesions with no progression or decrease in size.
measure: Kaplan-Meier Estimate of Duration of Response
time frame: From the first dose of pomalidomide to the data cut-off date of 15 March 2019; median overall time on follow-up was 4.86 months (3.78, 5.65, 4.04, and 8.38 months in each group respectively).
description: Duration of response is defined as the time from the date of the first objective response (complete response or partial response) to disease progression, for participants with a response. Participants who did not have disease progression or had not died were censored at the time of their last disease assessment or at the time of start of new anticancer therapy, whichever occurred first. Progressive disease (PD): ≥ 25% increase in the size of the measurable lesions taking as a reference the smallest disease measurement recorded since the start of protocol therapy (nadir), or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions, or if spine MRI and/or lumbar cerebrospinal fluid (CSF) cytology were previously negative and became positive.
measure: Kaplan-Meier Estimate of Progression-Free Survival (PFS)
time frame: From the first dose of pomalidomide to the data cut-off date of 15 March 2019; median overall time on follow-up was 4.86 months (3.78, 5.65, 4.04, and 8.38 months in each group respectively).
description: Progression-free survival was defined as the time from the date of first dose of pomalidomide until the date progressive disease (PD) was first observed or until the date of death due to any cause, whichever occurred first. Participants who did not have PD or had not died at the time of analysis were censored at the time of their last disease assessment or at the start of new anticancer therapy, whichever occurred first. Progressive Disease (PD): ≥ 25% increase in the size of the measurable lesions taking as a reference the smallest disease measurement recorded since the start of protocol therapy (nadir), or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions, or if spine MRI and/or lumbar CSF cytology were previously negative and became positive.
measure: Kalan-Meier Estimate of Overall Survival
time frame: From the first dose of pomalidomide to the data cut-off date of 15 March 2019; median overall time on follow-up was 4.86 months (3.78, 5.65, 4.04, and 8.38 months in each group respectively).
description: Overall survival was defined as the time from the date of the first dose to the date of death (any cause). Participants who were alive were censored at the last known time that the participant was alive.
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
time frame: From first dose of pomalidomide until 28 days after the last dose; median treatment duration was 84 days in the DIPG group, 112.0 days in the ependymoma group, 40.5 days in the high-grade glioma group and 57.0 days in the medulloblastoma group.
description: Treatment-emergent adverse events were defined as any adverse events (AE) occurring from the first dose of pomalidomide until 28 days after the last dose. The severity of each AE was graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03 and according to the following scale: Grade 1: Mild (transient or mild discomfort; no limitation in activity or medical intervention required); Grade 2: Moderate (mild to moderate limitation in activity, assistance may be needed; minimal medical intervention required); Grade 3: Severe (marked limitation in activity, assistance and medical intervention required, hospitalization possible); Grade 4: Life-threatening (extreme limitation in activity, significant assistance or medical intervention required, hospitalization or hospice care probable); Grade 5: Death. Drug-related AEs are those suspected by the Investigator as being related to administration of study drug.
arm group label: Pomalidomide
arm group type: Experimental
description: Pomalidomide will administered at a starting dose of 2.6 m2/day. Pomalidomide will be provided as either a capsule (0.5 mg, 1 mg, 2 mg, 3 mg or 4 mg) or as an oral suspension (2 mg/mL).
intervention type: Drug
intervention name: Pomalidomide
description: : Subjects will be administered pomalidomide on Days 1 to 21, followed by a 7-day rest period, of each 28-day treatment cycle and will continue treatment for up to 24 cycles or until disease progression, withdrawal of consent/assent or unresolved toxicities as described in the protocol.
arm group label: Pomalidomide
other name: CC-4047
intervention type: Drug
intervention name: Pomalidomide
description: Pomalidomide will be provided as gelatin capsules and as an oral suspension. The starting dose will be 2.6 mg/m²/day, administered on Days 1 to 21, followed by a 7-day rest period, of each 28-day treatment cycle.
arm group label: Pomalidomide
other name: CC-4047
other name: Pomalyst®
criteria: 
gender: All
minimum age: 1 Year
maximum age: 21 Years
healthy volunteers: No
last name: Bristol-Myers Squibb
role: Study Director
affiliation: Bristol-Myers Squibb
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country: France
country: Italy
country: Spain
country: United Kingdom
country: United States
url: https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
description: BMS Clinical Trial Information
url: https://www.bmsstudyconnect.com/s/US/English/USenHome
description: BMS Clinical Trial Patient Recruiting
url: https://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm
description: FDA Safety Alerts and Recalls
responsible party type: Sponsor
mesh term: Brain Neoplasms
mesh term: Medulloblastoma
mesh term: Nervous System Neoplasms
mesh term: Central Nervous System Neoplasms
mesh term: Thalidomide
mesh term: Pomalidomide
provided document: 
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participant flow: 
baseline: 
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reported events: 
certain agreements: 
point of contact: 