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

Primary Purpose

Ependymoma, Recurrent Childhood, Ependymoma

Status

Active

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

Granulocyte Macrophage Colony Stimulation Factor

About this trial

This is an interventional treatment trial for Ependymoma, Recurrent Childhood focused on measuring granulocyte macrophage colony stimulation factor, Incomplete resection

Eligibility Criteria

12 Months - 21 Years (Child, Adult)All SexesDoes not accept 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

Sites / Locations

Children's Hospital Colorado
Arnold Palmer Hospital for Children

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

GM-CSF treatment at second-look surgery arm

GM-CSF treatment at recurrence arm.

Arm 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

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

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

Full Information

NCT ID

NCT04408092

First Posted

December 10, 2019

Last Updated

January 30, 2023

Sponsor

University of Colorado, Denver

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT04408092

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

June 25, 2013 (Actual)

Primary Completion Date

September 21, 2021 (Actual)

Study Completion Date

December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Colorado, Denver

Collaborators

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

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Ependymoma, Recurrent Childhood, Ependymoma

Keywords

granulocyte macrophage colony stimulation factor, Incomplete resection

7. Study Design

Primary Purpose

Treatment

Study Phase

Early Phase 1

Interventional Study Model

Parallel Assignment

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)

Allocation

Non-Randomized

Enrollment

6 (Actual)

8. Arms, Groups, and Interventions

Arm Title

GM-CSF treatment at second-look surgery arm

Arm Type

Experimental

Arm Description

Arm Title

GM-CSF treatment at recurrence arm.

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Granulocyte Macrophage Colony Stimulation Factor

Other Intervention Name(s)

GM-CSF

Intervention 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.

Primary Outcome Measure Information:

Title

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

Description

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

Time Frame

8 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

12 Months

Maximum Age & Unit of Time

21 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Nicholas Foreman, MD

Organizational Affiliation

University of Colorado, Denver

Official's Role

Principal Investigator

Facility Information:

Facility Name

Children's Hospital Colorado

City

Denver

State/Province

Colorado

ZIP/Postal Code

80045

Country

United States

Facility Name

Arnold Palmer Hospital for Children

City

Orlando

State/Province

Florida

ZIP/Postal Code

32806

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

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

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