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

• Sponsor: Fred Hutchinson Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00669669
• Collaborator: (none)
• Enrollment: 12
• Location: 1
• Arm: 1
• Actual Duration (Months): 142.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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

PRIMARY OBJECTIVES:

1. 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).

2. 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:

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

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

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

4. Observe patients for clinical anti-tumor response.

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

6. 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 Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: N/A
• 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: Feb 25, 2009
• Actual Primary Completion Date: Jul 6, 2018
• Actual Study Completion Date: Jan 20, 2021

Arms and Interventions

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 CONFORMAL 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 Names: 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: 6-O-BENZYLGUANINE 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

Outcome Measures

Primary Outcome Measures

1. 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)

2. Number of Participants With Retrovirus or Leukemia [Up to 2 years after infusion]

   Replication competent retrovirus or diagnosis of leukemia

Secondary Outcome Measures

1. Response Rate [Up to 66 months]

   Number of patients with reduction in tumor burden of a predefined amount

2. 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.

3. Time to Progression [Up to 66 months.]

   From the first day of treatment (transplant) until unequivocal progression is documented, assessed up to 66 months.

4. Number of Participants That Survived [Up to 74 months]

   From the first day of treatment until death, assessed up to 74 months.

5. Number of Participants With Chemoprotection [Up to 66 months]

   assessed by the ability to increase the Temozolomide dose beyond 472 mg/m^2

6. 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

7. 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.

8. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fred Hutch/University of Washington Cancer Consortium	Seattle	Washington	United States	98109

Sponsors and Collaborators

• Fred Hutchinson Cancer Center

Investigators

• Principal Investigator: Hans-Peter Kiem, Fred Hutch/University of Washington Cancer Consortium

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 20, 2016

More Information

Publications

None provided.

• Responsible Party: Fred Hutchinson Cancer Center
• ClinicalTrials.gov Identifier: NCT00669669
• Other Study ID Numbers: 2000.00; NCI-2013-00701; 8357; 2000.00; RG1709046
• First Posted: Apr 30, 2008
• Last Update Posted: May 18, 2022
• Last Verified: Jan 1, 2022

• Additional relevant MeSH terms: Glioblastoma; Glioma; Gliosarcoma; Plerixafor; Temozolomide; Carmustine; O(6)-benzylguanine; Lenograstim

Study Results

Participant Flow

Arm/Group Title	Treatment (Chemotherapy, Autologous Stem Cell Transplant)
Arm/Group Description	See Detailed Description 3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal IMRT Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous in vitro-treated peripheral blood stem cell transplant Carmustine: Given IV Filgrastim: Given SC In Vitro-Treated Peripheral Blood Stem Cell Transplantation: Undergo autologous in vitro-treated peripheral blood stem cell transplant Intensity-Modulated Radiation Therapy: Undergo 3D conformal IMRT Laboratory Biomarker Analysis: Correlative studies O6-Benzylguanine: Given IV Plerixafor: Given SC Proton Beam Radiation Therapy: Undergo proton beam radiation therapy Temozolomide: Given PO
Period Title: Overall Study
STARTED	12
COMPLETED	11
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Treatment (Chemotherapy, Autologous Stem Cell Transplant)
Arm/Group Description	See Detailed Description 3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal IMRT Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous in vitro-treated peripheral blood stem cell transplant Carmustine: Given IV Filgrastim: Given SC In Vitro-Treated Peripheral Blood Stem Cell Transplantation: Undergo autologous in vitro-treated peripheral blood stem cell transplant Intensity-Modulated Radiation Therapy: Undergo 3D conformal IMRT Laboratory Biomarker Analysis: Correlative studies O6-Benzylguanine: Given IV Plerixafor: Given SC Proton Beam Radiation Therapy: Undergo proton beam radiation therapy Temozolomide: Given PO
Overall Participants	12
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	12 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	4 33.3%
Male	8 66.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 8.3%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	10 83.3%
More than one race	1 8.3%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Dose-limiting Toxicity (DLT)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Chemotherapy, Autologous Stem Cell Transplant)
Arm/Group Description	See Detailed Description 3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal IMRT Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous in vitro-treated peripheral blood stem cell transplant Carmustine: Given IV Filgrastim: Given SC In Vitro-Treated Peripheral Blood Stem Cell Transplantation: Undergo autologous in vitro-treated peripheral blood stem cell transplant Intensity-Modulated Radiation Therapy: Undergo 3D conformal IMRT Laboratory Biomarker Analysis: Correlative studies O6-Benzylguanine: Given IV Plerixafor: Given SC Proton Beam Radiation Therapy: Undergo proton beam radiation therapy Temozolomide: Given PO
Measure Participants	11
Count of Participants [Participants]	1 8.3%

2. Primary Outcome

Title	Number of Participants With Retrovirus or Leukemia
Description	Replication competent retrovirus or diagnosis of leukemia
Time Frame	Up to 2 years after infusion

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Chemotherapy, Autologous Stem Cell Transplant)
Arm/Group Description	See Detailed Description 3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal IMRT Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous in vitro-treated peripheral blood stem cell transplant Carmustine: Given IV Filgrastim: Given SC In Vitro-Treated Peripheral Blood Stem Cell Transplantation: Undergo autologous in vitro-treated peripheral blood stem cell transplant Intensity-Modulated Radiation Therapy: Undergo 3D conformal IMRT Laboratory Biomarker Analysis: Correlative studies O6-Benzylguanine: Given IV Plerixafor: Given SC Proton Beam Radiation Therapy: Undergo proton beam radiation therapy Temozolomide: Given PO
Measure Participants	11
Count of Participants [Participants]	0 0%

3. Secondary Outcome

Title	Response Rate
Description	Number of patients with reduction in tumor burden of a predefined amount
Time Frame	Up to 66 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Chemotherapy, Autologous Stem Cell Transplant)
Arm/Group Description	See Detailed Description 3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal IMRT Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous in vitro-treated peripheral blood stem cell transplant Carmustine: Given IV Filgrastim: Given SC In Vitro-Treated Peripheral Blood Stem Cell Transplantation: Undergo autologous in vitro-treated peripheral blood stem cell transplant Intensity-Modulated Radiation Therapy: Undergo 3D conformal IMRT Laboratory Biomarker Analysis: Correlative studies O6-Benzylguanine: Given IV Plerixafor: Given SC Proton Beam Radiation Therapy: Undergo proton beam radiation therapy Temozolomide: Given PO
Measure Participants	11
Count of Participants [Participants]	1 8.3%

4. Secondary Outcome

Title	Duration of Response
Description	From the onset of temozolomide to the date at which unequivocal disease progression, assessed up to 65 months.
Time Frame	Up to 65 months

Outcome Measure Data

Analysis Population Description

Reduction in number of patients assessed relative to total patients enrolled is due to some patient's disease progressing prior to start of temozolomide.

Arm/Group Title	Treatment (Chemotherapy, Autologous Stem Cell Transplant)
Arm/Group Description	See Detailed Description 3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal IMRT Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous in vitro-treated peripheral blood stem cell transplant Carmustine: Given IV Filgrastim: Given SC In Vitro-Treated Peripheral Blood Stem Cell Transplantation: Undergo autologous in vitro-treated peripheral blood stem cell transplant Intensity-Modulated Radiation Therapy: Undergo 3D conformal IMRT Laboratory Biomarker Analysis: Correlative studies O6-Benzylguanine: Given IV Plerixafor: Given SC Proton Beam Radiation Therapy: Undergo proton beam radiation therapy Temozolomide: Given PO
Measure Participants	6
Median (Full Range) [months]	4.5

5. Secondary Outcome

Title	Time to Progression
Description	From the first day of treatment (transplant) until unequivocal progression is documented, assessed up to 66 months.
Time Frame	Up to 66 months.

Outcome Measure Data

Analysis Population Description

Reduction in number of patients assessed relative to total patients enrolled is due to some patient's disease progressing prior to start of temozolomide.

Arm/Group Title	Treatment (Chemotherapy, Autologous Stem Cell Transplant)
Arm/Group Description	See Detailed Description 3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal IMRT Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous in vitro-treated peripheral blood stem cell transplant Carmustine: Given IV Filgrastim: Given SC In Vitro-Treated Peripheral Blood Stem Cell Transplantation: Undergo autologous in vitro-treated peripheral blood stem cell transplant Intensity-Modulated Radiation Therapy: Undergo 3D conformal IMRT Laboratory Biomarker Analysis: Correlative studies O6-Benzylguanine: Given IV Plerixafor: Given SC Proton Beam Radiation Therapy: Undergo proton beam radiation therapy Temozolomide: Given PO
Measure Participants	6
Median (Full Range) [months]	5.5

6. Secondary Outcome

Title	Number of Participants That Survived
Description	From the first day of treatment until death, assessed up to 74 months.
Time Frame	Up to 74 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Chemotherapy, Autologous Stem Cell Transplant)
Arm/Group Description	See Detailed Description 3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal IMRT Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous in vitro-treated peripheral blood stem cell transplant Carmustine: Given IV Filgrastim: Given SC In Vitro-Treated Peripheral Blood Stem Cell Transplantation: Undergo autologous in vitro-treated peripheral blood stem cell transplant Intensity-Modulated Radiation Therapy: Undergo 3D conformal IMRT Laboratory Biomarker Analysis: Correlative studies O6-Benzylguanine: Given IV Plerixafor: Given SC Proton Beam Radiation Therapy: Undergo proton beam radiation therapy Temozolomide: Given PO
Measure Participants	11
Count of Participants [Participants]	0 0%

7. Secondary Outcome

Title	Number of Participants With Chemoprotection
Description	assessed by the ability to increase the Temozolomide dose beyond 472 mg/m^2
Time Frame	Up to 66 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Chemotherapy, Autologous Stem Cell Transplant)
Arm/Group Description	See Detailed Description 3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal IMRT Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous in vitro-treated peripheral blood stem cell transplant Carmustine: Given IV Filgrastim: Given SC In Vitro-Treated Peripheral Blood Stem Cell Transplantation: Undergo autologous in vitro-treated peripheral blood stem cell transplant Intensity-Modulated Radiation Therapy: Undergo 3D conformal IMRT Laboratory Biomarker Analysis: Correlative studies O6-Benzylguanine: Given IV Plerixafor: Given SC Proton Beam Radiation Therapy: Undergo proton beam radiation therapy Temozolomide: Given PO
Measure Participants	11
Count of Participants [Participants]	2 16.7%

8. Secondary Outcome

Title	Number of Participants With Chemoselection
Description	assessed by the increase in peripheral blood Vector Copy Number (VCN), the average copies of integrated transgene per cell, after chemotherapy
Time Frame	Up to 59 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Chemotherapy, Autologous Stem Cell Transplant)
Arm/Group Description	See Detailed Description 3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal IMRT Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous in vitro-treated peripheral blood stem cell transplant Carmustine: Given IV Filgrastim: Given SC In Vitro-Treated Peripheral Blood Stem Cell Transplantation: Undergo autologous in vitro-treated peripheral blood stem cell transplant Intensity-Modulated Radiation Therapy: Undergo 3D conformal IMRT Laboratory Biomarker Analysis: Correlative studies O6-Benzylguanine: Given IV Plerixafor: Given SC Proton Beam Radiation Therapy: Undergo proton beam radiation therapy Temozolomide: Given PO
Measure Participants	11
Count of Participants [Participants]	4 33.3%

9. Secondary Outcome

Title	Gene Transfer Efficiency
Description	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.
Time Frame	Up to 59 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Chemotherapy, Autologous Stem Cell Transplant)
Arm/Group Description	See Detailed Description 3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal IMRT Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous in vitro-treated peripheral blood stem cell transplant Carmustine: Given IV Filgrastim: Given SC In Vitro-Treated Peripheral Blood Stem Cell Transplantation: Undergo autologous in vitro-treated peripheral blood stem cell transplant Intensity-Modulated Radiation Therapy: Undergo 3D conformal IMRT Laboratory Biomarker Analysis: Correlative studies O6-Benzylguanine: Given IV Plerixafor: Given SC Proton Beam Radiation Therapy: Undergo proton beam radiation therapy Temozolomide: Given PO
Measure Participants	11
Mean (Standard Error) [copies/cell]	0.78 (0.11)

10. Secondary Outcome

Title	Gene Transfer Efficiency After Chemotherapy
Description	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.
Time Frame	Up to 59 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Chemotherapy, Autologous Stem Cell Transplant)
Arm/Group Description	See Detailed Description 3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal IMRT Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous in vitro-treated peripheral blood stem cell transplant Carmustine: Given IV Filgrastim: Given SC In Vitro-Treated Peripheral Blood Stem Cell Transplantation: Undergo autologous in vitro-treated peripheral blood stem cell transplant Intensity-Modulated Radiation Therapy: Undergo 3D conformal IMRT Laboratory Biomarker Analysis: Correlative studies O6-Benzylguanine: Given IV Plerixafor: Given SC Proton Beam Radiation Therapy: Undergo proton beam radiation therapy Temozolomide: Given PO
Measure Participants	11
Mean (Standard Error) [copies/cell]	0.50 (0.13)

Adverse Events

Time Frame	Serious and other Adverse Events are collected through study completion, on average 2 years. All cause mortality was assessed up to 7 years.
Arm/Group Title	Treatment (Chemotherapy, Autologous Stem Cell Transplant)
Arm/Group Description	See Detailed Description 3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal IMRT Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous in vitro-treated peripheral blood stem cell transplant Carmustine: Given IV Filgrastim: Given SC In Vitro-Treated Peripheral Blood Stem Cell Transplantation: Undergo autologous in vitro-treated peripheral blood stem cell transplant Intensity-Modulated Radiation Therapy: Undergo 3D conformal IMRT Laboratory Biomarker Analysis: Correlative studies O6-Benzylguanine: Given IV Plerixafor: Given SC Proton Beam Radiation Therapy: Undergo proton beam radiation therapy Temozolomide: Given PO
All Cause Mortality
	Treatment (Chemotherapy, Autologous Stem Cell Transplant)
	Affected / at Risk (%)	# Events
Total	11/11 (100%)
Serious Adverse Events
	Treatment (Chemotherapy, Autologous Stem Cell Transplant)
	Affected / at Risk (%)	# Events
Total	0/11 (0%)
Other (Not Including Serious) Adverse Events
	Treatment (Chemotherapy, Autologous Stem Cell Transplant)
	Affected / at Risk (%)	# Events
Total	11/11 (100%)
Blood and lymphatic system disorders
Heme & Lymphatics	11/11 (100%)	162
Cardiac disorders
Cardiovascular	2/11 (18.2%)	8
Ear and labyrinth disorders
HEENT	5/11 (45.5%)	57
Endocrine disorders
Endocrine	2/11 (18.2%)	7
Gastrointestinal disorders
Digestive	7/11 (63.6%)	18
General disorders
General	5/11 (45.5%)	8
Metabolism and nutrition disorders
Metabolic & Nutritional	11/11 (100%)	155
Musculoskeletal and connective tissue disorders
Musculoskeletal	6/11 (54.5%)	15
Nervous system disorders
Nervous	8/11 (72.7%)	43
Reproductive system and breast disorders
Urogenital	4/11 (36.4%)	9
Respiratory, thoracic and mediastinal disorders
Respiratory	2/11 (18.2%)	7
Skin and subcutaneous tissue disorders
Skin & Appendages	7/11 (63.6%)	12

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.