Genetically Engineered Cells (P140K MGMT Hematopoietic Stem Cells), O6-Benzylguanine, Temozolomide, and Carmustine for the Treatment of Resected Supratentorial Glioblastoma or Gliosarcoma

Inclusion Criteria

• Patients with histologically confirmed, newly diagnosed, supratentorial glioblastoma or gliosarcoma who have undergone gross total tumor resection or near gross total resection (resection of > 85% of enhancing tumor demonstrated by MRI) are eligible up to 35 days post-operatively. Patients with primarily infratentorial disease, or with multifocal, or leptomeningeal dissemination of disease will be excluded. In general, patients will not have > 1 cm residual measurable or evaluable disease after surgical tumor resection
• Patient must have unmethylated MGMT
• Absence of IDH1 or IDH2 mutation on tumor tissue by a Clinical Laboratory Improvement Act (CLIA)-approved immunohistochemistry or DNA sequencing test on local testing
• Patients aged 18-75 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1 or Karnofsky >= 70
• No myelosuppressive chemotherapy or hematopoietic cell transplantation prior to the diagnosis of GBM and no prior chemotherapy (including Gliadel bis-chloronitrosourea [BCNU] wafers) for GBM
• Life expectancy of at least 12 weeks
• No plan for hypofractionated radiation therapy
• Absolute neutrophil count (ANC) >= 1500/mm^3 (obtained within 28 days prior to registration) * Note: the use of granulocyte colony-stimulating factor (G-CSF) or other intervention to achieve absolute neutrophil count (ANC) >= 1,500 cells/mm^3 is acceptable)
• Platelets >= 100,000/mm^3 (obtained within 28 days prior to registration) (Note: the use of transfusion or other intervention to achieve platelets >= 100,000 cells/mm^3 is acceptable)
• Hemoglobin (Hgb) >= 10.0 g/dl (obtained within 28 days prior to registration) (Note: the use of transfusion or other intervention to achieve Hgb >= 10.0 g/dl is acceptable)
• Bilirubin =< 2.0 upper limit of normal (ULN) (obtained within 28 days prior to registration)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN (obtained within 28 days prior to registration)
• Patients of child-bearing potential must agree to using single barrier contraception from time of trial entry to completion of the last cycle of chemotherapy
• Must be willing and able to understand provide informed consent
• Patient must be considered to be clinically stable
• The subject will be identified as a candidate for an autologous transplant via an evaluation by a transplant physician per standard of care
• No evidence of active, uncontrolled infection
• Availability of 10 unstained slides or formalin-fixed paraffin-embedded (FFPE) sample of tumor for molecular or histopathological studies
• Negative screening for active hepatitis B, C and human immunodeficiency virus (HIV)

Exclusion Criteria

• Any known medical or hereditary condition associated with immunosuppression; or other medical illness which may jeopardize patient safety
• Known history of HIV seropositivity
• Pregnant or lactating women. There is data to indicate that BCNU and TMZ is teratogenic and carcinogenic. Thus, its use in pregnant women would confer unnecessary risk to the fetus
• Patients with a corrected carbon monoxide (DLCO) or forced expiratory volume in 1 second (FEV1) < 50% of predicted
• Patients with known diagnosis heart failure or cardiac insufficiency and an left ventricular ejection fraction (LVEF) of < 40%. History of acute coronary event including myocardial infarction (MI) within 6 months prior to study enrollment
• Inability to undergo repeated MRI evaluation; or allergy or intolerance of gadolinium-containing contrast agent
• Active illicit drug use or diagnosis of active alcoholism
• Prior diagnosis of any malignant disease with the exception of non-melanomatous skin cancer, or carcinoma in situ of the cervix, bladder, prostate, or breast, unless patient has been disease-free/in remission for >= 2 years prior to date of study enrollment
• Mental incapacity or psychiatric illness preventing informed consent