G-CSF After Chemo-radiation in Patients With Glioblastoma

Inclusion Criteria:

• Participants must have confirmed newly diagnosed glioblastoma multiforme (GBM),World Health Organization (WHO) grade 4, IDH wildtype, either by histological ormolecular criteria.

• Molecular analysis needs to confirm a positive MGMT promoter methylation statususing standard institutional testing methods.

• Treatment needs to involve a planned 6-week course of standard of care radiationtherapy with concurrent and adjuvant 6 monthly chemotherapy with temozolomide.Patients scheduled to receive an abbreviated radiation course (e.g., 3 weeks inelderly patients) are eligible.

• Age ≥18 years. GBM is considered a biologically distinct disease in children.Children are excluded from this study but will be eligible for future pediatricclinical trials.

• Karnofsky Performance Status (KPS) > 60, see Appendix A

• No prior cranial irradiation.

• No existing diagnosis of clinical dementia or high clinical suspicion for presenceof any neurodegenerative disease (e.g., Alzheimer's Disease, Fronto-temporalDementia (FTD), Parkinson's Disease, Motor Neuron Disease, etc.) prior to diagnosisof GBM.

• Life expectancy of greater than 6 months.

• Must be able to undergo repeated brain Magnetic resonance imaging (MRI) studies withadministration of gadolinium (contrast enhanced brain MRI).

• Participants must have adequate organ and bone marrow function (as defined below) tobe able to receive standard chemoradiation therapy:

• leukocytes ≥2,500/mcL

• absolute neutrophil count≥1,500/mcL

• platelets ≥100,000/mcL

• total bilirubin≤ institutional upper limit of normal (ULN)

• AST(SGOT)/ALT(SGPT)≤3 × institutional ULN creatinine≤ institutional ULN OR

• glomerular filtration rate (GFR) ≥60 mL/min/1.73 m2 unless data existssupporting safe use at lower kidney function values, no lower than 30mL/min/1.73 m2.

For patients with Gilbert's syndrome, total bilirubin can be ≤ 3xULN.

• For participants with evidence of chronic hepatitis B virus (HBV) infection byhistory, the HBV viral load must be undetectable on suppressive therapy, ifindicated.

• Participants with a prior or concurrent malignancy whose natural history ortreatment does not have the potential to interfere with the safety or efficacyassessment of the investigational regimen (use of granulocyte colony stimulatingfactor (G-CSF)) are eligible for this trial.

• Ability to understand and the willingness to sign a written informed consentdocument.

Exclusion Criteria:

• Participants who are receiving any other investigational agents.

• History of allergic reactions attributed to compounds of similar chemical orbiologic composition to G-CSF (Filgrastim associated allergic reactions).

• Participants with uncontrolled intercurrent illness that could influence leukocytecounts, such as severe infection requiring intravenous antibiotics, or known HIV (human immunodeficiency virus), since HIV/AIDS is an immunocompromising diseaseaffecting lymphocyte counts (one of the correlative biomarkers in this study)

• Pregnant women are excluded from this study because of the use of cytotoxicchemotherapy (temozolomide) and radiation, given as part of standard of care in thistrial, is of teratogenic potential or has abortifacient effects. Because there is arisk for adverse events in nursing infants secondary to treatment of the mother withcytotoxic chemotherapy, breastfeeding should be discontinued if the mother istreated with cytotoxic chemotherapy.

• Participants must be able to undergo repeated neurocognitive testing in English (orSpanish). As cognitive outcome is one of the main secondary endpoints of this study,the lack of normative and comparison data for non-English or non-Spanish-speakingpatients would confound this outcome in our small sample size (see StatisticalAnalysis Plan for more details). Presence of significant aphasia or any otherlanguage impairment at time of diagnosis with GBM is considered an exclusioncriterion. Any concerns or questions about a subject's ability to participate inneurocognitive testing can be directed to the study investigators for furtherdiscussion and clarification.

• Participants with active thromboembolic event (pulmonary embolism or deep venousthrombosis) or prior thromboembolic event within 6 months prior to diagnosis of GBMmay need to be excluded because of possible risks of thromboembolism with the use ofG-CSF and will require further discussion with the PI prior to enrollment on acase-by-case basis.

• Participants with the following medical conditions are excluded and not eligiblebased on elevated risk of G-CSF associated toxicity: Sickle cell disease or sicklecell trait, congenital neutropenia, hematological malignancy (leukemia ormyelodysplastic syndrome).

• Patients who are dependent on high doses of corticosteroids equivalent to 8mg ofdaily dexamethasone or more, or who are expected to be unable to taper steroidspost-operatively to a dose of 4mg of dexamethasone or less prior to start ofchemo-RT.