Trial Outcomes & Findings for O6-Benzylguanine-Mediated Tumor Sensitization With Chemoprotected Autologous Stem Cell in Treating Patients With Malignant Gliomas (NCT NCT00669669)

Results Overview

Defined as any grade 4 nonhematopoietic toxicity that is likely related to the investigational procedures (Part I)

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

12 participants

Primary outcome timeframe

Up to 6 weeks after infusion

Results posted on

2022-05-18

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment (Chemotherapy, Autologous Stem Cell Transplant) 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 Study STARTED	12
Overall Study COMPLETED	11
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment (Chemotherapy, Autologous Stem Cell Transplant) 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 Study To late to start treatment	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Chemotherapy, Autologous Stem Cell Transplant) n=12 Participants 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
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	12 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	10 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 6 weeks after infusion

Defined as any grade 4 nonhematopoietic toxicity that is likely related to the investigational procedures (Part I)

Outcome measures

Outcome measures
Measure	Treatment (Chemotherapy, Autologous Stem Cell Transplant) n=11 Participants 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
Number of Participants Dose-limiting Toxicity (DLT)	1 Participants

PRIMARY outcome

Timeframe: Up to 2 years after infusion

Replication competent retrovirus or diagnosis of leukemia

Outcome measures

Outcome measures
Measure	Treatment (Chemotherapy, Autologous Stem Cell Transplant) n=11 Participants 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
Number of Participants With Retrovirus or Leukemia	0 Participants

SECONDARY outcome

Timeframe: Up to 66 months

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

Outcome measures

Outcome measures
Measure	Treatment (Chemotherapy, Autologous Stem Cell Transplant) n=11 Participants 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
Response Rate	1 Participants

SECONDARY outcome

Timeframe: Up to 65 months

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

From the onset of temozolomide to the date at which unequivocal disease progression, assessed up to 65 months.

Outcome measures

Outcome measures
Measure	Treatment (Chemotherapy, Autologous Stem Cell Transplant) n=6 Participants 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
Duration of Response	4.5 months Interval 2.5 to 65.2

SECONDARY outcome

Timeframe: Up to 66 months.

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

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

Outcome measures

Outcome measures
Measure	Treatment (Chemotherapy, Autologous Stem Cell Transplant) n=6 Participants 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
Time to Progression	5.5 months Interval 3.8 to 66.1

SECONDARY outcome

Timeframe: Up to 74 months

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

Outcome measures

Outcome measures
Measure	Treatment (Chemotherapy, Autologous Stem Cell Transplant) n=11 Participants 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
Number of Participants That Survived	0 Participants

SECONDARY outcome

Timeframe: Up to 66 months

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

Outcome measures

Outcome measures
Measure	Treatment (Chemotherapy, Autologous Stem Cell Transplant) n=11 Participants 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
Number of Participants With Chemoprotection	2 Participants

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Treatment (Chemotherapy, Autologous Stem Cell Transplant) n=11 Participants 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
Number of Participants With Chemoselection	4 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Treatment (Chemotherapy, Autologous Stem Cell Transplant) n=11 Participants 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
Gene Transfer Efficiency	0.78 copies/cell Standard Error 0.11

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Treatment (Chemotherapy, Autologous Stem Cell Transplant) n=11 Participants 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
Gene Transfer Efficiency After Chemotherapy	0.50 copies/cell Standard Error 0.13

Adverse Events

Treatment (Chemotherapy, Autologous Stem Cell Transplant)

Serious events: 0 serious events

Other events: 11 other events

Deaths: 11 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Treatment (Chemotherapy, Autologous Stem Cell Transplant) n=11 participants at risk 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
Cardiac disorders Cardiovascular	18.2% 2/11 • Number of events 8 • Serious and other Adverse Events are collected through study completion, on average 2 years. All cause mortality was assessed up to 7 years.
Gastrointestinal disorders Digestive	63.6% 7/11 • Number of events 18 • Serious and other Adverse Events are collected through study completion, on average 2 years. All cause mortality was assessed up to 7 years.
Endocrine disorders Endocrine	18.2% 2/11 • Number of events 7 • Serious and other Adverse Events are collected through study completion, on average 2 years. All cause mortality was assessed up to 7 years.
General disorders General	45.5% 5/11 • Number of events 8 • Serious and other Adverse Events are collected through study completion, on average 2 years. All cause mortality was assessed up to 7 years.
Ear and labyrinth disorders HEENT	45.5% 5/11 • Number of events 57 • Serious and other Adverse Events are collected through study completion, on average 2 years. All cause mortality was assessed up to 7 years.
Blood and lymphatic system disorders Heme & Lymphatics	100.0% 11/11 • Number of events 162 • Serious and other Adverse Events are collected through study completion, on average 2 years. All cause mortality was assessed up to 7 years.
Metabolism and nutrition disorders Metabolic & Nutritional	100.0% 11/11 • Number of events 155 • Serious and other Adverse Events are collected through study completion, on average 2 years. All cause mortality was assessed up to 7 years.
Musculoskeletal and connective tissue disorders Musculoskeletal	54.5% 6/11 • Number of events 15 • Serious and other Adverse Events are collected through study completion, on average 2 years. All cause mortality was assessed up to 7 years.
Nervous system disorders Nervous	72.7% 8/11 • Number of events 43 • Serious and other Adverse Events are collected through study completion, on average 2 years. All cause mortality was assessed up to 7 years.
Respiratory, thoracic and mediastinal disorders Respiratory	18.2% 2/11 • Number of events 7 • Serious and other Adverse Events are collected through study completion, on average 2 years. All cause mortality was assessed up to 7 years.
Skin and subcutaneous tissue disorders Skin & Appendages	63.6% 7/11 • Number of events 12 • Serious and other Adverse Events are collected through study completion, on average 2 years. All cause mortality was assessed up to 7 years.
Reproductive system and breast disorders Urogenital	36.4% 4/11 • Number of events 9 • Serious and other Adverse Events are collected through study completion, on average 2 years. All cause mortality was assessed up to 7 years.

Additional Information

Hans-Peter Kiem, M.D., Ph.D.

Fred Hutch Cancer Research Center

Phone: 206.667.4425

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place