hSTAR GBM (Hematopoetic Stem Cell (HPC) Rescue for GBM)

Inclusion Criteria:

• Patients with histologically confirmed, newly diagnosed, supratentorial glioblastomaor gliosarcoma who have undergone gross total tumor resection or near gross totalresection (resection of >85% of enhancing tumor demonstrated by MRI) are eligible upto 35 days post-operatively. Patients with primarily infratentorial disease, or withmultifocal,or leptomeningeal dissemination of disease will be excluded. In general,patients will not have > 1 cm residual measurable or evaluable disease aftersurgical tumor resection.

• Patient must have unmethylated MGMT

• Absence Of IDH1 or IDH2mutation on tumor tissue by a CLIA-approvedimmunohistochemistry or DNA sequencing test on local testing

• Patients aged 18-75 years.

• ECOG performance status 0-1or Karnofsky ≥ 70.

• No myelosuppressive chemotherapy or hematopoietic cell transplantation prior to thediagnosis of GBM and no prior chemotherapy (including Gliadel BCNU wafers) for GBM

• Life expectancy of at least 12 weeks.

• No plan for hypofractionated radiation therapy

• Adequate hematologic (absolute neutrophil count (ANC)≥ 1000/mm3, platelets ≥ 100,000/mm3, Hgb ≥ 9.5, hepatic (Bilirubin ≤ 2.0 mg/dl, AST and ALT less than orequal to 3 times institutional upper limit of normal, prothrombin time <1.2 timesnormal), and renal (serum creatinine ≤ 2.0 mg/dl or Creatinine Clearance ≥ 60mL/min/1.73 m2for subjects with serum creatinine levels above institutionalnormal). These tests will be repeated within 2 weeks of treatment with BG and TMZ,and must meet the same criteria. -Post-operative steroids are i) tapered to ≤ 8mgdexamethasone/day(or equivalent)and ii) patient has been on a stable or decreasingsteroid dose for the 7 days prior to enrollment

• Patients of child-bearing potential must agree to using single barriercontraception.

• Must be willing and able to understand provide informed consent.

• Patient must have all sutures removed prior to registration

• Patient must be considered to be clinically stable.

• The subject will be identified as a candidate for an autologous transplant via anevaluation by a transplant physician per standard of care. Participants will bescreened by their transplant physician and social work for a history of substanceabuse per screening tool such as SIPAT. Any participant with positive screen forsignificant substance abuse will undergo evaluation and must have a treatment,management plan in place and must have formal review of medical team prior toinitiation of transplant procedures.

• No evidence of active infection.

• Availability of 10unstained slides or FFPE sample of tumor for molecular orhistopathological studies.

• Negative screening for Hepatitis B, C and HIV

Exclusion Criteria:

• Any known medical or hereditary condition associated withimmunosuppression;orothermedical illness which may jeopardize patient safety.

• Known history of HIV seropositivity. This exclusion is included for two reasons.First, there is evidence of decreased marrow reserve in HIV+ patients and antiviraltreatment is associated with myelosuppression. Thus, drug treatment designed to bemyelosuppressive may bemore toxic in this patient population. Second, extensivelaboratory culturing of the bone marrow and peripheral blood progenitor cells isrequired. No preclinical samples which are HIV+ have been evaluated with the genetransfer modality proposed and thus the feasibility and safety of gene transfer andselection in HIV+ samples cannot yet be advocated. Such studies are planned so as tonot preclude HIV+ patients in later studies.

• Pregnant or lactating women. There is data to indicate that BCNU and TMZ isteratogenic and carcinogenic. Thus, its use in pregnant women would conferunnecessary risk to the fetus.

• Patients with symptomatic pulmonary disease and other severe co-morbid respiratoryconditions, including patients with active pulmonary infection and/or pulse oximetry < 90% and a corrected DLCO < 50% of predicted. However, subjects with a correctedDLCO in the range of 50-70% should have Pulmonologyclearance prior to intervention.

• Patients with known diagnosis heart failure or cardiac insufficiency and an LVEF of < 40%. History of acute coronary event including MI within 6 months prior to studyenrollment.

• Known history of cardiac arrhythmias including atrial fibrillation,tachyarrhythmiaor bradycardia.Inability to undergo repeated MRI evaluation; orallergy or intolerance of Gadolinium-containing contrast agent.

• Active illicit drug use or diagnosis of alcoholism.

• Prior diagnosis of any malignant disease with the exception of non-melanomatous skincancer, or carcinoma in situof the cervix, bladder, prostate, or breast, unlesspatient has been disease-free/in remission for ≥2 years prior to date of studyenrollment.

• Mental incapacity or psychiatric illness preventing informed consent.

• History of Hepatitis B or C or Hepatitis grade ≥3 are excluded due to the potentialfor additional hepatotixicity