Clinical Trials /

Study of the Effect of GM-CSF on Macrophages in Ependymoma

NCT04408092

Description:

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

Related Conditions:
  • Ependymoma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of the Effect of GM-CSF on Macrophages in Ependymoma
  • Official Title: Pilot Study of the Effect of GM-CSF on Macrophages in Incompletely Resected or Recurrent Ependymoma

Clinical Trial IDs

  • ORG STUDY ID: 13-0133.cc
  • SECONDARY ID: P30CA046934
  • NCT ID: NCT04408092

Conditions

  • Ependymoma, Recurrent Childhood
  • Ependymoma

Interventions

DrugSynonymsArms
Granulocyte Macrophage Colony Stimulation FactorGM-CSFGM-CSF treatment at recurrence arm.

Purpose

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

Detailed Description

      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.
    

Trial Arms

NameTypeDescriptionInterventions
GM-CSF treatment at second-look surgery armExperimentalNewly 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
  • Granulocyte Macrophage Colony Stimulation Factor
GM-CSF treatment at recurrence arm.ExperimentalEPN 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
  • Granulocyte Macrophage Colony Stimulation Factor

Eligibility Criteria

        Inclusion Criteria:

          -  Age > 12 months and < 21 years at the time of study enrollment.

          -  Patients must be one of the following:

             • Newly diagnosed with posterior fossa ependymoma with a subtotal resection at initial
             surgery. These patients will be eligible for stratum 1.

               -  Be in first relapse of their posterior fossa ependymoma. These patients will be
                  eligible for stratum 2.

          -  Histologically confirmed diagnosis of intracranial ependymoma .

          -  Pre or post-operative MR imaging of the brain demonstrates no evidence of
             non-contiguous spread beyond the primary site

          -  Pre or post-operative MR imaging of the spine demonstrates no evidence of
             non-contiguous spread beyond the primary site

          -  Pre-operative CSF cytology obtained from the lumbar CSF space demonstrated no evidence
             of non-contiguous spread beyond the primary site.

             • The requirement for lumbar CSF examination may be waived if deemed to be medically
             contraindicated.

          -  Patients must meet one of the following performance scores.

             • ECOG performance status scores of 0, 1, or 2.

               -  Karnofsky score of ≥ 50 for patients > 16 years of age or Lansky score of ≥ 50
                  for patients ≤ 16 years of age

          -  Organ Function Requirements:

        Adequate renal function defined as:

          -  Creatinine clearance or radioisotope GFR ³ 70ml/min/1.73 m2 or

          -  A serum creatinine based on age/gender as follows:

        Age Maximum Serum Creatinine (mg/dL) Male Female

        1 month to < 6 months 0.4 0.4 6 months to < 1 year 0.5 0.5

        1 to < 2 years 0.6 0.6 2 to < 6 years 0.8 0.8 6 to < 10 years 1 1 10 to < 13 years 1.2 1.2
        13 to < 16 years 1.5 1.4

        ≥ 16 years 1.7 1.4 The threshold creatinine values in this Table were derived from the
        Schwartz formula for estimating GFR (Schwartz et al. J. Peds, 106:522, 1985) utilizing
        child length and stature data published by the CDC.

          -  Adequate liver function defined as:

          -  Total bilirubin =< 1.5 x upper limit of normal (ULN) for age, and

          -  SGOT (AST) or SGPT (ALT) < 3 x upper limit of normal (ULN) for age.

          -  Patients with Gilbert syndrome or hemolytic anemia are eligible if total bilirubin is
             < 3 x upper limit of normal (ULN) for age.

          -  Adequate Bone Marrow Function defined as:

          -  Peripheral absolute neutrophil count (ANC) >= 1,000/uL

          -  Platelet count >= 100,000/uL (transfusion independent).

        Exclusion Criteria:

          -  Patients with a diagnosis of spinal cord ependymoma, myxopapillary ependymoma,
             subependymoma, ependymoblastoma, supratentorial ependymoma, or mixed glioma are NOT
             eligible.

          -  Patients with evidence of metastatic disease by MRI or CSF cytology are NOT eligible
      
Maximum Eligible Age:21 Years
Minimum Eligible Age:12 Months
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with increased M/M infiltration compared to institutional and ACNS0121 controls
Time Frame:8 years
Safety Issue:
Description:Outcome measure is met if cell count is >50 AIF1+ microglia per high power field (40x)

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Colorado, Denver

Trial Keywords

  • granulocyte macrophage colony stimulation factor
  • Incomplete resection

Last Updated

May 28, 2020