This trial is active, not recruiting.

Conditions glioblastoma, gliosarcoma
Treatments 3-dimensional conformal radiation therapy, autologous hematopoietic stem cell transplantation, carmustine, filgrastim, in vitro-treated peripheral blood stem cell transplantation, intensity-modulated radiation therapy, laboratory biomarker analysis, o6-benzylguanine, plerixafor, proton beam radiation therapy, temozolomide
Phase phase 1/phase 2
Sponsor Fred Hutchinson Cancer Research Center
Collaborator National Cancer Institute (NCI)
Start date February 2009
End date December 2017
Trial size 24 participants
Trial identifier NCT00669669, 2000.00, 8357, NCI-2013-00701, P30CA015704


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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
See Detailed Description
3-dimensional conformal radiation therapy 3-dimensional radiation therapy
Undergo 3D conformal IMRT
autologous hematopoietic stem cell transplantation Autologous Stem Cell Transplantation
Undergo autologous in vitro-treated peripheral blood stem cell transplant
carmustine BCNU
Given IV
filgrastim Filgrastim XM02
Given SC
in vitro-treated peripheral blood stem cell transplantation in vitro-treated PBPC transplantation
Undergo autologous in vitro-treated peripheral blood stem cell transplant
intensity-modulated radiation therapy IMRT
Undergo 3D conformal IMRT
laboratory biomarker analysis
Correlative studies
o6-benzylguanine 6-O-BENZYLGUANINE
Given IV
plerixafor AMD 3100
Given SC
proton beam radiation therapy
Undergo proton beam radiation therapy
temozolomide CCRG-81045
Given PO

Primary Outcomes

Chemoprotection, assessed by the ability to increase the temozolomide dose beyond 472 mg/m^2
time frame: Up to 96 weeks
Duration of response
time frame: From the onset of temozolomide to the date at which unequivocal disease progression, assessed up to 15 years
Gene transfer efficiency and in vivo selection, assessed by gene marking in peripheral blood and marrow
time frame: Up to 15 years
Incidence of DLT (Part Ii)
time frame: 56 days
Incidence of dose-limiting toxicity (DLT) defined as any grade 4 nonhematopoietic toxicity that is likely related to the investigational procedures (Part I)
time frame: Up to 6 weeks after infusion
Incidence of replication competent retrovirus or leukemia
time frame: Up to 15 years
Response rate
time frame: Up to 15 years
time frame: From the first day of treatment until death, assessed up to 15 years
Time to progression
time frame: From the first day of treatment until unequivocal progression is documented, assessed up to 15 years

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

Official title Benzylguanine-Mediated Tumor Sensitization With Chemoprotected Autologous Stem Cells for Patients With Malignant Gliomas
Principal investigator Hans-Peter Kiem
Description 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.
Trial information was received from ClinicalTrials.gov and was last updated in June 2016.
Information provided to ClinicalTrials.gov by Fred Hutchinson Cancer Research Center.
Location data was received from the National Cancer Institute and was last updated in August 2016.