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

Sponsor

University of Colorado, Denver (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT04408092

Collaborator

National Cancer Institute (NCI) (NIH), Children's Hospital Colorado (Other)

Enrollment

Locations

Arms

137.2

Anticipated Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Ependymoma, Recurrent Childhood Ependymoma	Drug: Granulocyte Macrophage Colony Stimulation Factor	Early Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

6 participants

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.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

Official Title:

Pilot Study of the Effect of GM-CSF on Macrophages in Incompletely Resected or Recurrent Ependymoma

Actual Study Start Date :

Jun 25, 2013

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
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	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 Names: GM-CSF
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	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 Names: GM-CSF

Arm

Intervention/Treatment

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

Drug: Granulocyte Macrophage Colony Stimulation Factor

Other Names:

GM-CSF

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

Drug: Granulocyte Macrophage Colony Stimulation Factor

Other Names:

GM-CSF

Outcome Measures

Primary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Months to 21 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital Colorado	Denver	Colorado	United States	80045
2	Arnold Palmer Hospital for Children	Orlando	Florida	United States	32806

Sponsors and Collaborators

University of Colorado, Denver
National Cancer Institute (NCI)
Children's Hospital Colorado

Investigators

Principal Investigator: Nicholas Foreman, MD, University of Colorado, Denver

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

University of Colorado, Denver

ClinicalTrials.gov Identifier:

NCT04408092

Other Study ID Numbers:

13-0133.cc
P30CA046934

First Posted:

May 29, 2020

Last Update Posted:

Feb 9, 2022

Last Verified:

Feb 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by University of Colorado, Denver

granulocyte macrophage colony stimulation factor

Incomplete resection

Additional relevant MeSH terms:

Ependymoma

Study Results

No Results Posted as of Feb 9, 2022