Ignite Creation Date:
2025-12-24 @ 11:03 PM
Ignite Modification Date:
2026-01-04 @ 9:21 AM
Study NCT ID:
NCT00669669
Status:
TERMINATED
Last Update Posted:
2022-05-18
First Post:
2008-04-29
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
O6-Benzylguanine-Mediated Tumor Sensitization With Chemoprotected Autologous Stem Cell in Treating Patients With Malignant Gliomas
Sponsor:
Fred Hutchinson Cancer Center
Organization:
Study Overview
Official Title:
Benzylguanine-Mediated Tumor Sensitization With Chemoprotected Autologous Stem Cells for Patients With Malignant Gliomas
Status:
TERMINATED
Status Verified Date:
2022-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Terminated due to loss in funding.
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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.
Detailed 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.
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.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: