<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/NCT04408092</url>
  </required_header>
  <id_info>
    <org_study_id>13-0133.cc</org_study_id>
    <secondary_id>P30CA046934</secondary_id>
    <nct_id>NCT04408092</nct_id>
  </id_info>
  <brief_title>Study of the Effect of GM-CSF on Macrophages in Ependymoma</brief_title>
  <official_title>Pilot Study of the Effect of GM-CSF on Macrophages in Incompletely Resected or Recurrent Ependymoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Colorado, Denver</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Children's Hospital Colorado</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Colorado, Denver</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 plans to learn more about the use of Granulocyte Macrophage Colony Stimulation&#xD;
      Factor (GM-CSF) on ependymoma tumors. The use of GM-CSF is a potential way of increasing the&#xD;
      infiltration of immune cells and this study is looking at whether or not this will improve&#xD;
      the outcome of patients with an ependymoma&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      To study whether Granulocyte Macrophage Colony Stimulation Factor (GM-CSF) increases&#xD;
      macrophage infiltration in children with ependymoma (EPN) who are to have planned surgery as&#xD;
      a standard procedure for incomplete resection or recurrent tumor. To correlate the extent of&#xD;
      macrophage infiltration with other immune markers of the tumor at subsequent surgery with&#xD;
      outcome. This is intended as a pilot protocol with the potential to be incorporated in the&#xD;
      next COG (Children's Oncology Group) national ependymoma studies.&#xD;
&#xD;
      Recombinant Granulocyte Macrophage Colony Stimulation Factor (rGM-CSF) is a hematopoietic&#xD;
      growth factor which supports survival, clonal expansion, and differentiation of hematopoietic&#xD;
      progenitor cells. rGM-CSF induces partially committed progenitor cells to divide and&#xD;
      differentiate in the granulocyte-macrophage pathways. rGM-CSF stimulates the production of&#xD;
      monocytes, granulocytes, erythrocytes, and sometimes, megakaryocytes in the bone marrow. It&#xD;
      also induces mature macrophages to increase phagocytosis, superoxide generation, Antibody&#xD;
      Dependent Cell-mediated Cytotoxicity (ADCC), tumoricidal killing and cytokine production&#xD;
      (IL-1 and tumor necrosis factor).&#xD;
&#xD;
      Registration of all participants must occur before any study-related procedures. Staff will&#xD;
      be available to register participants Monday thru Friday, from 8:00 AM to 5:00 PM Mountain&#xD;
      Standard Time.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">June 25, 2013</start_date>
  <completion_date type="Anticipated">December 2024</completion_date>
  <primary_completion_date type="Actual">September 21, 2021</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>standard treatment of EPN includes repeat surgeries at (1) second-look surgery to remove residual tumor after first-look surgery at initial diagnosis, and (2) optimal debulking of recurrent tumor, providing a rare opportunity to measure the effect of experimental therapy directly in children's brain tumors. Ten patients each will be entered into the second-look and recurrence strata of this study.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with increased M/M infiltration compared to institutional and ACNS0121 controls</measure>
    <time_frame>8 years</time_frame>
    <description>Outcome measure is met if cell count is &gt;50 AIF1+ microglia per high power field (40x)</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Ependymoma, Recurrent Childhood</condition>
  <condition>Ependymoma</condition>
  <arm_group>
    <arm_group_label>GM-CSF treatment at second-look surgery arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Newly diagnosed patients with EPN who have a subtotal resection at initial presentation and are without evidence of metastatic tumor will be enrolled in this stratum. Total patient population in this stratum will be 10 patients. It should be noted that prior experience suggests that about 1/3 of newly presenting patients still have residual tumor after the initial surgery</description>
  </arm_group>
  <arm_group>
    <arm_group_label>GM-CSF treatment at recurrence arm.</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>EPN patients with a first regional relapse and without evidence of metastatic tumor will be enrolled in this stratum. Total patient population will be 10 patients.&#xD;
Patients with a first recurrence will have the recurrence confirmed by the local institutional neuro-radiologists. They will have the entire neuro-axis scanned and a spinal tap performed (where safe) to exclude metastatic tumor. They will then receive 5 days of GM-CSF and then proceed to surgery if deemed clinically indicated by the treating physician</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Granulocyte Macrophage Colony Stimulation Factor</intervention_name>
    <description>Recombinant Granulocyte Macrophage Colony Stimulation Factor (rGM-CSF) is a hematopoietic growth factor which supports survival, clonal expansion, and differentiation of hematopoietic progenitor cells. rGM-CSF induces partially committed progenitor cells to divide and differentiate in the granulocyte-macrophage pathways. rGM-CSF stimulates the production of monocytes, granulocytes, erythrocytes, and sometimes, megakaryocytes in the bone marrow. It also induces mature macrophages to increase phagocytosis, superoxide generation, Antibody Dependent Cell-mediated Cytotoxicity (ADCC), tumoricidal killing and cytokine production (IL-1 and tumor necrosis factor). GM-CSF was used in the first successful phase III trial of immunotherapy in the pediatric COG protocol, ANBL0931, a national study in high risk neuroblastoma.</description>
    <arm_group_label>GM-CSF treatment at recurrence arm.</arm_group_label>
    <arm_group_label>GM-CSF treatment at second-look surgery arm</arm_group_label>
    <other_name>GM-CSF</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &gt; 12 months and &lt; 21 years at the time of study enrollment.&#xD;
&#xD;
          -  Patients must be one of the following:&#xD;
&#xD;
             • Newly diagnosed with posterior fossa ependymoma with a subtotal resection at initial&#xD;
             surgery. These patients will be eligible for stratum 1.&#xD;
&#xD;
               -  Be in first relapse of their posterior fossa ependymoma. These patients will be&#xD;
                  eligible for stratum 2.&#xD;
&#xD;
          -  Histologically confirmed diagnosis of intracranial ependymoma .&#xD;
&#xD;
          -  Pre or post-operative MR imaging of the brain demonstrates no evidence of&#xD;
             non-contiguous spread beyond the primary site&#xD;
&#xD;
          -  Pre or post-operative MR imaging of the spine demonstrates no evidence of&#xD;
             non-contiguous spread beyond the primary site&#xD;
&#xD;
          -  Pre-operative CSF cytology obtained from the lumbar CSF space demonstrated no evidence&#xD;
             of non-contiguous spread beyond the primary site.&#xD;
&#xD;
             • The requirement for lumbar CSF examination may be waived if deemed to be medically&#xD;
             contraindicated.&#xD;
&#xD;
          -  Patients must meet one of the following performance scores.&#xD;
&#xD;
             • ECOG performance status scores of 0, 1, or 2.&#xD;
&#xD;
               -  Karnofsky score of ≥ 50 for patients &gt; 16 years of age or Lansky score of ≥ 50&#xD;
                  for patients ≤ 16 years of age&#xD;
&#xD;
          -  Organ Function Requirements:&#xD;
&#xD;
        Adequate renal function defined as:&#xD;
&#xD;
          -  Creatinine clearance or radioisotope GFR ³ 70ml/min/1.73 m2 or&#xD;
&#xD;
          -  A serum creatinine based on age/gender as follows:&#xD;
&#xD;
        Age Maximum Serum Creatinine (mg/dL) Male Female&#xD;
&#xD;
        1 month to &lt; 6 months 0.4 0.4 6 months to &lt; 1 year 0.5 0.5&#xD;
&#xD;
        1 to &lt; 2 years 0.6 0.6 2 to &lt; 6 years 0.8 0.8 6 to &lt; 10 years 1 1 10 to &lt; 13 years 1.2 1.2&#xD;
        13 to &lt; 16 years 1.5 1.4&#xD;
&#xD;
        ≥ 16 years 1.7 1.4 The threshold creatinine values in this Table were derived from the&#xD;
        Schwartz formula for estimating GFR (Schwartz et al. J. Peds, 106:522, 1985) utilizing&#xD;
        child length and stature data published by the CDC.&#xD;
&#xD;
          -  Adequate liver function defined as:&#xD;
&#xD;
          -  Total bilirubin =&lt; 1.5 x upper limit of normal (ULN) for age, and&#xD;
&#xD;
          -  SGOT (AST) or SGPT (ALT) &lt; 3 x upper limit of normal (ULN) for age.&#xD;
&#xD;
          -  Patients with Gilbert syndrome or hemolytic anemia are eligible if total bilirubin is&#xD;
             &lt; 3 x upper limit of normal (ULN) for age.&#xD;
&#xD;
          -  Adequate Bone Marrow Function defined as:&#xD;
&#xD;
          -  Peripheral absolute neutrophil count (ANC) &gt;= 1,000/uL&#xD;
&#xD;
          -  Platelet count &gt;= 100,000/uL (transfusion independent).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with a diagnosis of spinal cord ependymoma, myxopapillary ependymoma,&#xD;
             subependymoma, ependymoblastoma, supratentorial ependymoma, or mixed glioma are NOT&#xD;
             eligible.&#xD;
&#xD;
          -  Patients with evidence of metastatic disease by MRI or CSF cytology are NOT eligible&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Months</minimum_age>
    <maximum_age>21 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nicholas Foreman, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Colorado, Denver</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Children's Hospital Colorado</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arnold Palmer Hospital for Children</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>December 10, 2019</study_first_submitted>
  <study_first_submitted_qc>May 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 29, 2020</study_first_posted>
  <last_update_submitted>January 30, 2023</last_update_submitted>
  <last_update_submitted_qc>January 30, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 31, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>granulocyte macrophage colony stimulation factor</keyword>
  <keyword>Incomplete resection</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ependymoma</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT04408092
org study id: 13-0133.cc
secondary id: P30CA046934
nct id: NCT04408092
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study plans to learn more about the use of Granulocyte Macrophage Colony Stimulation
      Factor (GM-CSF) on ependymoma tumors. The use of GM-CSF is a potential way of increasing the
      infiltration of immune cells and this study is looking at whether or not this will improve
      the outcome of patients with an ependymoma
To study whether Granulocyte Macrophage Colony Stimulation Factor (GM-CSF) increases
      macrophage infiltration in children with ependymoma (EPN) who are to have planned surgery as
      a standard procedure for incomplete resection or recurrent tumor. To correlate the extent of
      macrophage infiltration with other immune markers of the tumor at subsequent surgery with
      outcome. This is intended as a pilot protocol with the potential to be incorporated in the
      next COG (Children's Oncology Group) national ependymoma studies.

      Recombinant Granulocyte Macrophage Colony Stimulation Factor (rGM-CSF) is a hematopoietic
      growth factor which supports survival, clonal expansion, and differentiation of hematopoietic
      progenitor cells. rGM-CSF induces partially committed progenitor cells to divide and
      differentiate in the granulocyte-macrophage pathways. rGM-CSF stimulates the production of
      monocytes, granulocytes, erythrocytes, and sometimes, megakaryocytes in the bone marrow. It
      also induces mature macrophages to increase phagocytosis, superoxide generation, Antibody
      Dependent Cell-mediated Cytotoxicity (ADCC), tumoricidal killing and cytokine production
      (IL-1 and tumor necrosis factor).

      Registration of all participants must occur before any study-related procedures. Staff will
      be available to register participants Monday thru Friday, from 8:00 AM to 5:00 PM Mountain
      Standard Time.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: standard treatment of EPN includes repeat surgeries at (1) second-look surgery to remove residual tumor after first-look surgery at initial diagnosis, and (2) optimal debulking of recurrent tumor, providing a rare opportunity to measure the effect of experimental therapy directly in children's brain tumors. Ten patients each will be entered into the second-look and recurrence strata of this study.
primary purpose: Treatment
masking: None (Open Label)
measure: Number of participants with increased M/M infiltration compared to institutional and ACNS0121 controls
time frame: 8 years
description: Outcome measure is met if cell count is >50 AIF1+ microglia per high power field (40x)
arm group label: GM-CSF treatment at second-look surgery arm
arm group type: Experimental
description: Newly diagnosed patients with EPN who have a subtotal resection at initial presentation and are without evidence of metastatic tumor will be enrolled in this stratum. Total patient population in this stratum will be 10 patients. It should be noted that prior experience suggests that about 1/3 of newly presenting patients still have residual tumor after the initial surgery
arm group label: GM-CSF treatment at recurrence arm.
arm group type: Experimental
description: EPN patients with a first regional relapse and without evidence of metastatic tumor will be enrolled in this stratum. Total patient population will be 10 patients.
Patients with a first recurrence will have the recurrence confirmed by the local institutional neuro-radiologists. They will have the entire neuro-axis scanned and a spinal tap performed (where safe) to exclude metastatic tumor. They will then receive 5 days of GM-CSF and then proceed to surgery if deemed clinically indicated by the treating physician
intervention type: Drug
intervention name: Granulocyte Macrophage Colony Stimulation Factor
description: Recombinant Granulocyte Macrophage Colony Stimulation Factor (rGM-CSF) is a hematopoietic growth factor which supports survival, clonal expansion, and differentiation of hematopoietic progenitor cells. rGM-CSF induces partially committed progenitor cells to divide and differentiate in the granulocyte-macrophage pathways. rGM-CSF stimulates the production of monocytes, granulocytes, erythrocytes, and sometimes, megakaryocytes in the bone marrow. It also induces mature macrophages to increase phagocytosis, superoxide generation, Antibody Dependent Cell-mediated Cytotoxicity (ADCC), tumoricidal killing and cytokine production (IL-1 and tumor necrosis factor). GM-CSF was used in the first successful phase III trial of immunotherapy in the pediatric COG protocol, ANBL0931, a national study in high risk neuroblastoma.
arm group label: GM-CSF treatment at recurrence arm.
arm group label: GM-CSF treatment at second-look surgery arm
other name: GM-CSF
criteria: 
gender: All
minimum age: 12 Months
maximum age: 21 Years
healthy volunteers: No
last name: Nicholas Foreman, MD
role: Principal Investigator
affiliation: University of Colorado, Denver
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Ependymoma
sharing ipd: No