O6-Benzylguanine-Mediated Tumor Sensitization With Chemoprotected Autologous Stem Cell in Treating Patients With Malignant Gliomas

Phase 1

Terminated

• Conditions: Gliosarcoma; Glioblastoma
• Interventions: 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

• Registration Number: NCT00669669
• Lead Sponsor: Fred Hutchinson Cancer 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...

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).
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Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2008-04-29
• Study First Submitted QC: 2008-04-29
• Study First Posted: 2008-04-30
• Study Start: 2009-02-25
• Primary Completion: 2018-07-06
• Results First Submitted: 2018-11-07
• Results First Submitted QC: 2018-12-06
• Results First Posted: 2018-12-28
• Study Completion: 2021-01-20
• Status Verified: 2022-01
• Last Update Submitted: 2022-04-29
• Last Update Posted: 2022-05-18

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 12

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (chemotherapy, autologous stem cell transplant)	Laboratory Biomarker Analysis	See Detailed Description
Treatment (chemotherapy, autologous stem cell transplant)	Autologous Hematopoietic Stem Cell Transplantation	See Detailed Description
Treatment (chemotherapy, autologous stem cell transplant)	3-Dimensional Conformal Radiation Therapy	See Detailed Description
Treatment (chemotherapy, autologous stem cell transplant)	Intensity-Modulated Radiation Therapy	See Detailed Description
Treatment (chemotherapy, autologous stem cell transplant)	Proton Beam Radiation Therapy	See Detailed Description
Treatment (chemotherapy, autologous stem cell transplant)	Filgrastim	See Detailed Description
Treatment (chemotherapy, autologous stem cell transplant)	In Vitro-Treated Peripheral Blood Stem Cell Transplantation	See Detailed Description
Treatment (chemotherapy, autologous stem cell transplant)	O6-Benzylguanine	See Detailed Description
Treatment (chemotherapy, autologous stem cell transplant)	Temozolomide	See Detailed Description
Treatment (chemotherapy, autologous stem cell transplant)	Carmustine	See Detailed Description
Treatment (chemotherapy, autologous stem cell transplant)	Plerixafor	See Detailed Description

Primary Outcome Measures

Name	Time	Method
Number of Participants Dose-limiting Toxicity (DLT)	Up to 6 weeks after infusion	Defined as any grade 4 nonhematopoietic toxicity that is likely related to the investigational procedures (Part I)
Number of Participants With Retrovirus or Leukemia	Up to 2 years after infusion	Replication competent retrovirus or diagnosis of leukemia

Secondary Outcome Measures

Name	Time	Method
Response Rate	Up to 66 months	Number of patients with reduction in tumor burden of a predefined amount
Number of Participants With Chemoprotection	Up to 66 months	assessed by the ability to increase the Temozolomide dose beyond 472 mg/m\^2
Number of Participants That Survived	Up to 74 months	From the first day of treatment until death, assessed up to 74 months.
Time to Progression	Up to 66 months.	From the first day of treatment (transplant) until unequivocal progression is documented, assessed up to 66 months.
Number of Participants With Chemoselection	Up to 59 months	assessed by the increase in peripheral blood Vector Copy Number (VCN), the average copies of integrated transgene per cell, after chemotherapy
Duration of Response	Up to 65 months	From the onset of temozolomide to the date at which unequivocal disease progression, assessed up to 65 months.
Gene Transfer Efficiency	Up to 59 months	Assessed by gene marking in peripheral blood prior to chemoselection. Gene marking is assessed in whole blood by quantitative PCR and reported as a vector copy number (VCN) or the average copies of integrated transgene per cell. The units here will be reported as copies/cell.
Gene Transfer Efficiency After Chemotherapy	Up to 59 months	Assessed by gene marking in peripheral blood after chemoselection. Gene marking is assessed in whole blood by quantitative PCR and reported as a vector copy number (VCN) or the average copies of integrated transgene per cell. The units here will be reported as copies/cell.

Trial Locations

Locations (1)

Fred Hutch/University of Washington Cancer Consortium; 🇺🇸 Seattle, Washington, United States