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

NCT04408092 | Completed Early Phase 1 DMC FDA Drug

• 2 other identifiers: 13-0133.ccP30CA046934
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 2

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

Conditions

Ependymoma, Recurrent Childhood; Ependymoma

Keywords

granulocyte macrophage colony stimulation factor; Incomplete resection

Outcome Measures

Primary Outcomes (1)

• Number of participants with increased M/M infiltration compared to institutional and ACNS0121 controls

  Outcome measure is met if cell count is \>50 AIF1+ microglia per high power field (40x)

  8 years

Study Arms (2)

GM-CSF treatment at second-look surgery arm

EXPERIMENTAL

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

Drug: Granulocyte Macrophage Colony Stimulation Factor

GM-CSF treatment at recurrence arm.

EXPERIMENTAL

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

Drug: Granulocyte Macrophage Colony Stimulation Factor

Interventions

Granulocyte Macrophage Colony Stimulation Factor DRUG

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.

Also known as: GM-CSF

GM-CSF treatment at recurrence arm.; GM-CSF treatment at second-look surgery arm

Eligibility Criteria

• Age: 12 Months - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Colorado, Denver: lead
• National Cancer Institute (NCI): collaborator
• Children's Hospital Colorado: collaborator

Study Sites (2)

Children's Hospital Colorado

Denver, Colorado, 80045, United States

Location

Arnold Palmer Hospital for Children

Orlando, Florida, 32806, United States

Location

MeSH Terms

Conditions

Ependymoma

Interventions

Granulocyte-Macrophage Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Nicholas Foreman, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: December 10, 2019
• First Posted: May 29, 2020
• Study Start: June 25, 2013
• Primary Completion: September 21, 2021
• Study Completion: July 21, 2023
• Last Updated: March 15, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)