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Trial record 1 of 1 for:    NCT00669669
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O6-Benzylguanine-Mediated Tumor Sensitization With Chemoprotected Autologous Stem Cell in Treating Patients With Malignant Gliomas

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ClinicalTrials.gov Identifier: NCT00669669
Recruitment Status : Active, not recruiting
First Posted : April 30, 2008
Last Update Posted : January 9, 2018
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Glioblastoma Gliosarcoma Radiation: 3-Dimensional Conformal Radiation Therapy Procedure: Autologous Hematopoietic Stem Cell Transplantation Drug: Carmustine Biological: Filgrastim Procedure: In Vitro-Treated Peripheral Blood Stem Cell Transplantation Radiation: Intensity-Modulated Radiation Therapy Other: Laboratory Biomarker Analysis Drug: O6-Benzylguanine Drug: Plerixafor Radiation: Proton Beam Radiation Therapy Drug: Temozolomide Phase 1 Phase 2

Detailed Description:


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.


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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Benzylguanine-Mediated Tumor Sensitization With Chemoprotected Autologous Stem Cells for Patients With Malignant Gliomas
Actual Study Start Date : February 25, 2009
Estimated Primary Completion Date : March 24, 2018
Estimated Study Completion Date : December 31, 2027

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Treatment (chemotherapy, autologous stem cell transplant)
See Detailed Description
Radiation: 3-Dimensional Conformal Radiation Therapy
Undergo 3D conformal IMRT
Other Names:
  • 3-dimensional radiation therapy
  • 3D CRT
  • 3D-CRT
  • Conformal Therapy
  • Radiation Conformal Therapy
Procedure: Autologous Hematopoietic Stem Cell Transplantation
Undergo autologous in vitro-treated peripheral blood stem cell transplant
Other Name: Autologous Stem Cell Transplantation
Drug: Carmustine
Given IV
Other Names:
  • BCNU
  • Becenum
  • Becenun
  • BiCNU
  • Bis(chloroethyl) Nitrosourea
  • Bis-Chloronitrosourea
  • Carmubris
  • Carmustin
  • Carmustinum
  • FDA 0345
  • Gliadel
  • N,N'-Bis(2-chloroethyl)-N-nitrosourea
  • Nitrourean
  • Nitrumon
  • SK 27702
  • SRI 1720
  • WR-139021
Biological: Filgrastim
Given SC
Other Names:
  • Filgrastim XM02
  • G-CSF
  • Neupogen
  • r-metHuG-CSF
  • Recombinant Methionyl Human Granulocyte Colony Stimulating Factor
  • rG-CSF
  • Tbo-filgrastim
  • Tevagrastim
Procedure: In Vitro-Treated Peripheral Blood Stem Cell Transplantation
Undergo autologous in vitro-treated peripheral blood stem cell transplant
Other Names:
  • in vitro-treated PBPC transplantation
  • in vitro-treated peripheral blood progenitor cell transplantation
Radiation: Intensity-Modulated Radiation Therapy
Undergo 3D conformal IMRT
Other Names:
  • IMRT
  • Intensity Modulated RT
  • Intensity-Modulated Radiotherapy
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: O6-Benzylguanine
Given IV
Other Names:
  • O(6)-Benzylguanine
Drug: Plerixafor
Given SC
Other Names:
  • AMD 3100
  • JM-3100
  • Mozobil
  • SDZ SID 791
Radiation: Proton Beam Radiation Therapy
Undergo proton beam radiation therapy
Drug: Temozolomide
Given PO
Other Names:
  • CCRG-81045
  • Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-
  • M & B 39831
  • M and B 39831
  • Methazolastone
  • RP-46161
  • SCH 52365
  • Temcad
  • Temodal
  • Temodar
  • Temomedac

Primary Outcome Measures :
  1. 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 ]
  2. Incidence of DLT (Part II) [ Time Frame: 56 days ]
  3. Incidence of replication competent retrovirus or leukemia [ Time Frame: Up to 2 years after infusion ]

Secondary Outcome Measures :
  1. Response rate [ Time Frame: Up to 15 years ]
  2. Duration of response [ Time Frame: From the onset of temozolomide to the date at which unequivocal disease progression, assessed up to 15 years ]
  3. Survival [ Time Frame: From the first day of treatment until death, assessed up to 15 years ]
  4. Time to progression [ Time Frame: From the first day of treatment until unequivocal progression is documented, assessed up to 15 years ]
  5. Gene transfer efficiency and in vivo selection, assessed by gene marking in peripheral blood and marrow [ Time Frame: Up to 15 years ]
  6. Chemoprotection, assessed by the ability to increase the temozolomide dose beyond 472 mg/m^2 [ Time Frame: Up to 96 weeks ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00669669

United States, Washington
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Principal Investigator: Hans-Peter Kiem Fred Hutch/University of Washington Cancer Consortium

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT00669669     History of Changes
Other Study ID Numbers: 2000.00
NCI-2013-00701 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2000.00 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
P30CA015704 ( U.S. NIH Grant/Contract )
First Posted: April 30, 2008    Key Record Dates
Last Update Posted: January 9, 2018
Last Verified: January 2018

Additional relevant MeSH terms:
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
JM 3100
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors