Clinical trial NCT04408092: 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
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Ependymoma, Recurrent Childhood
Ependymoma
Keywords: granulocyte macrophage colony stimulation factor
Incomplete resection
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Children's Hospital Colorado
First posted: 2020-05-29
Enrollment: 6
Sex: ALL
Minimum age (years): 12
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of participants with increased M/M infiltration compared to institutional and ACNS0121 controls
timeFrame: 8 years
Secondary outcomes:
Other outcomes:
Locations:
city: Denver
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Orlando
country: United States
facility: Arnold Palmer Hospital for Children
state: Florida
Study officials:
affiliation: University of Colorado, Denver
name: Nicholas Foreman, MD
role: PRINCIPAL_INVESTIGATOR
References: