This phase I/II trial studies the side effects and best dose of temozolomide when given together with radiation therapy, carmustine, O6-benzylguanine, and patients' own stem cell (autologous) transplant in treating patients with newly diagnosed glioblastoma multiforme or gliosarcoma. Giving chemotherapy, such as temozolomide, carmustine, and O6-benzylguanine, and radiation therapy before a peripheral stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. Giving colony-stimulating factors, such as filgrastim or plerixafor, and certain chemotherapy drugs, helps stem cells move from the bone marrow to the blood so they can be collected and stored. Chemotherapy or radiation therapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy and radiation therapy.
Name: 3-Dimensional Conformal Radiation Therapy
Description: Undergo 3D conformal IMRTType: RadiationTreatment (chemotherapy, autologous stem cell transplant)
Name: Autologous Hematopoietic Stem Cell Transplantation
Description: Undergo autologous in vitro-treated peripheral blood stem cell transplantType: ProcedureTreatment (chemotherapy, autologous stem cell transplant)
Name: Carmustine
Description: Given IVType: DrugTreatment (chemotherapy, autologous stem cell transplant)
Name: Filgrastim
Description: Given SCType: BiologicalTreatment (chemotherapy, autologous stem cell transplant)
Name: In Vitro-Treated Peripheral Blood Stem Cell Transplantation
Description: Undergo autologous in vitro-treated peripheral blood stem cell transplantType: ProcedureTreatment (chemotherapy, autologous stem cell transplant)
Name: Intensity-Modulated Radiation Therapy
Description: Undergo 3D conformal IMRTType: RadiationTreatment (chemotherapy, autologous stem cell transplant)
Name: Laboratory Biomarker Analysis
Description: Correlative studiesType: OtherTreatment (chemotherapy, autologous stem cell transplant)
Name: O6-Benzylguanine
Description: Given IVType: DrugTreatment (chemotherapy, autologous stem cell transplant)
Name: Plerixafor
Description: Given SCType: DrugTreatment (chemotherapy, autologous stem cell transplant)
Name: Proton Beam Radiation Therapy
Description: Undergo proton beam radiation therapyType: RadiationTreatment (chemotherapy, autologous stem cell transplant)
Name: Temozolomide
Description: Given POType: DrugTreatment (chemotherapy, autologous stem cell transplant)
Description: Defined as any grade 4 nonhematopoietic toxicity that is likely related to the investigational procedures (Part I)
Measure: Number of Participants Dose-limiting Toxicity (DLT) Time: Up to 6 weeks after infusionDescription: Replication competent retrovirus or diagnosis of leukemia
Measure: Number of Participants With Retrovirus or Leukemia Time: Up to 2 years after infusionDescription: Proportion of patients with reduction in tumor burden of a predefined amount
Measure: Response Rate Time: Up to 15 yearsDescription: From the onset of temozolomide to the date at which unequivocal disease progression, assessed up to 15 years
Measure: Duration of Response Time: Up to 15 yearsDescription: From the first day of treatment until death, assessed up to 15 years
Measure: Number of Participants That Survived Time: Up to 15 yearsDescription: From the first day of treatment until unequivocal progression is documented, assessed up to 15 years
Measure: Time to Progression Time: Up to 15 yearsDescription: Assessed by gene marking in peripheral blood and marrow
Measure: Gene Transfer Efficiency and in Vivo Selection Time: Up to 15 yearsDescription: assessed by the ability to increase the Temozolomide dose beyond 472 mg/m^2
Measure: Number of Participants With Chemoprotection Time: Up to 15 yearsSingle Group Assignment
There is one SNP
Inclusion Criteria: - Patients with glioblastoma multiforme or gliosarcoma - The patient or legal guardian must be able to comprehend the informed consent form and sign prior to patient enrollment - Karnofsky performance status at time of study entry must be >= 70% - Life expectancy of >= 3 months - Patients must agree to undergo repeat clinical neurological examinations and brain magnetic resonance imaging (MRI) with appropriate contrast after every other cycle of chemotherapy - White blood cell (WBC) > 3000/ul - Absolute neutrophil count (ANC) > 1500/ul - Platelets > 100,000/ul - Hemoglobin > 10 gm/100ml - Total and direct bilirubin < 1.5 times upper limit of laboratory normal - Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) =< 3 times upper limit of laboratory normal - Alkaline phosphatase =< 3 times upper limit of laboratory normal - Blood urea nitrogen (BUN) < 1.5 times upper limit of laboratory normal - Serum creatinine < 1.5 times upper limit of laboratory normal - Left ventricular ejection fraction (LVEF) >= 40%, however, subjects with a LVEF in the range of 40-49% should have cardiology clearance prior to intervention - MGMT promoter methylation analysis of surgically resected tumor or tumor biopsy must demonstrate an unmethylated or hypomethylated MGMT promoter status Exclusion Criteria: - Patients with cardiac insufficiency and a LVEF of < 40%; history of coronary artery disease or arrhythmia, which has required or requires ongoing treatment - Patients with active pulmonary infection and/or pulse oximetry < 90% and a corrected diffusion capacity of the lung for carbon monoxide (DLCO) < 70% of predicted - Active systemic infection - Patients who are human immunodeficiency virus (HIV) positive - Pregnant or lactating women; a beta-human chorionic gonadotropin (HCG) level will be obtained from women of childbearing potential; fertile men and women should use effective contraception - Previous chemotherapy for any malignancy including temozolomide, dacarbazine (DTIC) or prior nitrosourea - Diabetes mellitus - Bleeding disorder - Methylated or hypermethylated MGMT promoter status within tumor tissue - Medical or psychiatric condition which in the opinion of the protocol chairman would compromise the patient's ability to tolerate this protocol - Prior interstitial radiotherapy, stereotactic or gamma knife surgery or implanted BCNU-wafers Inclusion Criteria: - Patients with glioblastoma multiforme or gliosarcoma - The patient or legal guardian must be able to comprehend the informed consent form and sign prior to patient enrollment - Karnofsky performance status at time of study entry must be >= 70% - Life expectancy of >= 3 months - Patients must agree to undergo repeat clinical neurological examinations and brain magnetic resonance imaging (MRI) with appropriate contrast after every other cycle of chemotherapy - White blood cell (WBC) > 3000/ul - Absolute neutrophil count (ANC) > 1500/ul - Platelets > 100,000/ul - Hemoglobin > 10 gm/100ml - Total and direct bilirubin < 1.5 times upper limit of laboratory normal - Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) =< 3 times upper limit of laboratory normal - Alkaline phosphatase =< 3 times upper limit of laboratory normal - Blood urea nitrogen (BUN) < 1.5 times upper limit of laboratory normal - Serum creatinine < 1.5 times upper limit of laboratory normal - Left ventricular ejection fraction (LVEF) >= 40%, however, subjects with a LVEF in the range of 40-49% should have cardiology clearance prior to intervention - MGMT promoter methylation analysis of surgically resected tumor or tumor biopsy must demonstrate an unmethylated or hypomethylated MGMT promoter status Exclusion Criteria: - Patients with cardiac insufficiency and a LVEF of < 40%; history of coronary artery disease or arrhythmia, which has required or requires ongoing treatment - Patients with active pulmonary infection and/or pulse oximetry < 90% and a corrected diffusion capacity of the lung for carbon monoxide (DLCO) < 70% of predicted - Active systemic infection - Patients who are human immunodeficiency virus (HIV) positive - Pregnant or lactating women; a beta-human chorionic gonadotropin (HCG) level will be obtained from women of childbearing potential; fertile men and women should use effective contraception - Previous chemotherapy for any malignancy including temozolomide, dacarbazine (DTIC) or prior nitrosourea - Diabetes mellitus - Bleeding disorder - Methylated or hypermethylated MGMT promoter status within tumor tissue - Medical or psychiatric condition which in the opinion of the protocol chairman would compromise the patient's ability to tolerate this protocol - Prior interstitial radiotherapy, stereotactic or gamma knife surgery or implanted BCNU-wafers Glioblastoma Gliosarcoma Glioblastoma Glioma Gliosarcoma PRIMARY OBJECTIVES: I. Determine the safety and feasibility of infusing autologous granulocyte colony-stimulating factor (G-CSF) (filgrastim) mobilized stem cells transduced with a Phoenix-gibbon ape leukemia virus (GALV)-pseudotype vector expressing methylguanine methyltransferase (MGMT) (P140K). --- P140K ---
V. Determine the correlation of the level of MGMT (P140K) marking with toxicity, temozolomide dose achieved, and response. --- P140K ---