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Trial record 1 of 5 for:    Recruiting, Enrolling by invitation Studies | Interventional Studies | Ependymoma | United States | First posted from 01/01/2020 to 06/24/2020
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Study of the Effect of GM-CSF on Macrophages in Ependymoma

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ClinicalTrials.gov Identifier: NCT04408092
Recruitment Status : Recruiting
First Posted : May 29, 2020
Last Update Posted : May 29, 2020
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Children's Hospital Colorado
Information provided by (Responsible Party):
University of Colorado, Denver

Tracking Information
First Submitted Date  ICMJE December 10, 2019
First Posted Date  ICMJE May 29, 2020
Last Update Posted Date May 29, 2020
Actual Study Start Date  ICMJE June 25, 2013
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 28, 2020)
Number of participants with increased M/M infiltration compared to institutional and ACNS0121 controls [ Time Frame: 8 years ]
Outcome measure is met if cell count is >50 AIF1+ microglia per high power field (40x)
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of the Effect of GM-CSF on Macrophages in Ependymoma
Official Title  ICMJE Pilot Study of the Effect of GM-CSF on Macrophages in Incompletely Resected or Recurrent Ependymoma
Brief Summary 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE 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.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Ependymoma, Recurrent Childhood
  • Ependymoma
Intervention  ICMJE Drug: Granulocyte Macrophage Colony Stimulation Factor
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.
Other Name: GM-CSF
Study Arms  ICMJE
  • Experimental: GM-CSF treatment at second-look surgery arm
    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
    Intervention: Drug: Granulocyte Macrophage Colony Stimulation Factor
  • Experimental: GM-CSF treatment at recurrence arm.

    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: Drug: Granulocyte Macrophage Colony Stimulation Factor
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 28, 2020)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Months to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Pamela Bowry 720-777-4159 bowry.pamela@childrenscolorado.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04408092
Other Study ID Numbers  ICMJE 13-0133.cc
P30CA046934 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of Colorado, Denver
Study Sponsor  ICMJE University of Colorado, Denver
Collaborators  ICMJE
  • National Cancer Institute (NCI)
  • Children's Hospital Colorado
Investigators  ICMJE Not Provided
PRS Account University of Colorado, Denver
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP