Clinical Trial Finder

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

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).

• II. Define the dose of BCNU (carmustine) that results in efficient engraftment of gene modified cells when given with peripheral blood stem cell support.

SECONDARY OBJECTIVES:

• I. Determine the engraftment of gene-modified cells after conditioning with BCNU.

• II. Determine the ability to select gene-modified cells in vivo with this regimen.

• III. Evaluate the molecular and clonal composition of gene-modified cells after chemotherapy with temozolomide.

• IV. Observe patients for clinical anti-tumor response.

• V. Determine the correlation of the level of MGMT (P140K) marking with toxicity, temozolomide dose achieved, and response.

• VI. Characterize the toxicity associated with this regimen.

OUTLINE: This is a phase I, dose-escalation study of temozolomide followed by a phase II study. PART I: Within 35 days of surgery, patients undergo 3 dimensional (3D) conformal intensity-modulated radiation therapy (IMRT) or proton beam radiation therapy daily 5 days per week for 6 weeks. Patients receive filgrastim subcutaneously (SC) on days -7 to -3 and begin stem cell collection on the 4th day of filgrastim administration (up to 3 apheresis). Patients may also receive plerixafor SC on days -5 to -3. The CD34+ stem cells are separated from the patient's stem cells and they are transduced with Phoenix-RD114 pseudotype vector (retrovirus). One day after apheresis is completed, patients receive carmustine intravenously (IV) over 3 hours followed 2 hours later by temozolomide orally (PO). At least twenty-four hours after completion of carmustine and temozolomide, patients undergo reinfusion of genetically-modified stem cells. PART II: Beginning approximately 4 weeks after completion of Phase 1 of the study, patients receive O6-benzylguanine IV continuously over 48 hours followed by temozolomide PO within 1 hour. Treatment may repeat at least every 28 days for a total of 24 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 1-3 months for 2 years, every 3-6 months for 3 years, and then annually thereafter for 10 years.

Arms

Experimental: Treatment (chemotherapy, autologous stem cell transplant)

See Detailed Description

Interventions

Radiation: - 3-Dimensional Conformal Radiation Therapy

Undergo 3D conformal IMRT

Procedure: - Autologous Hematopoietic Stem Cell Transplantation

Undergo autologous in vitro-treated peripheral blood stem cell transplant

Drug: - Carmustine

Given IV

Biological: - Filgrastim

Given SC

Procedure: - In Vitro-Treated Peripheral Blood Stem Cell Transplantation

Undergo autologous in vitro-treated peripheral blood stem cell transplant

Radiation: - Intensity-Modulated Radiation Therapy

Undergo 3D conformal IMRT

Other: - Laboratory Biomarker Analysis

Correlative studies

Drug: - O6-Benzylguanine

Given IV

Drug: - Plerixafor

Given SC

Radiation: - Proton Beam Radiation Therapy

Undergo proton beam radiation therapy

Drug: - Temozolomide

Given PO