Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2013-00701 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| 8357 | |||
| 2000.00 | Other Identifier | Fred Hutch/University of Washington Cancer Consortium | |
| RG1709046 | Other Identifier | Fred Hutch/University of Washington Cancer Consortium |
Not provided
Not provided
Not provided
Terminated due to loss in funding.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment (chemotherapy, autologous stem cell transplant) | Experimental | See Detailed Description |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 3-Dimensional Conformal Radiation Therapy | Radiation | Undergo 3D conformal IMRT |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Dose-limiting Toxicity (DLT) | Defined as any grade 4 nonhematopoietic toxicity that is likely related to the investigational procedures (Part I) | Up to 6 weeks after infusion |
| Number of Participants With Retrovirus or Leukemia | Replication competent retrovirus or diagnosis of leukemia | Up to 2 years after infusion |
| Measure | Description | Time Frame |
|---|---|---|
| Response Rate | Number of patients with reduction in tumor burden of a predefined amount | Up to 66 months |
| Duration of Response | From the onset of temozolomide to the date at which unequivocal disease progression, assessed up to 65 months. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Hans-Peter Kiem | Fred Hutch/University of Washington Cancer Consortium | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fred Hutch/University of Washington Cancer Consortium | Seattle | Washington | 98109 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25105369 | Derived | Adair JE, Johnston SK, Mrugala MM, Beard BC, Guyman LA, Baldock AL, Bridge CA, Hawkins-Daarud A, Gori JL, Born DE, Gonzalez-Cuyar LF, Silbergeld DL, Rockne RC, Storer BE, Rockhill JK, Swanson KR, Kiem HP. Gene therapy enhances chemotherapy tolerance and efficacy in glioblastoma patients. J Clin Invest. 2014 Sep;124(9):4082-92. doi: 10.1172/JCI76739. Epub 2014 Aug 8. |
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 20, 2016 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Autologous Hematopoietic Stem Cell Transplantation | Procedure | Undergo autologous in vitro-treated peripheral blood stem cell transplant |
|
|
| Carmustine | Drug | Given IV |
|
|
| Filgrastim | Biological | Given SC |
|
|
| In Vitro-Treated Peripheral Blood Stem Cell Transplantation | Procedure | Undergo autologous in vitro-treated peripheral blood stem cell transplant |
|
|
| Intensity-Modulated Radiation Therapy | Radiation | Undergo 3D conformal IMRT |
|
|
| Laboratory Biomarker Analysis | Other | Correlative studies |
|
| O6-Benzylguanine | Drug | Given IV |
|
|
| Plerixafor | Drug | Given SC |
|
|
| Proton Beam Radiation Therapy | Radiation | Undergo proton beam radiation therapy |
|
| Temozolomide | Drug | Given PO |
|
|
| Up to 65 months |
| Time to Progression | From the first day of treatment (transplant) until unequivocal progression is documented, assessed up to 66 months. | Up to 66 months. |
| Number of Participants That Survived | From the first day of treatment until death, assessed up to 74 months. | Up to 74 months |
| Number of Participants With Chemoprotection | assessed by the ability to increase the Temozolomide dose beyond 472 mg/m^2 | Up to 66 months |
| Number of Participants With Chemoselection | assessed by the increase in peripheral blood Vector Copy Number (VCN), the average copies of integrated transgene per cell, after chemotherapy | Up to 59 months |
| Gene Transfer Efficiency | 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. | Up to 59 months |
| Gene Transfer Efficiency After Chemotherapy | 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. | Up to 59 months |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants Dose-limiting Toxicity (DLT) | Defined as any grade 4 nonhematopoietic toxicity that is likely related to the investigational procedures (Part I) | Posted | Count of Participants | Participants | Up to 6 weeks after infusion |
|
|
| |||||||||||||||||||||||||||
| Primary | Number of Participants With Retrovirus or Leukemia | Replication competent retrovirus or diagnosis of leukemia | Posted | Count of Participants | Participants | Up to 2 years after infusion |
|
| ||||||||||||||||||||||||||||
| Secondary | Response Rate | Number of patients with reduction in tumor burden of a predefined amount | Posted | Count of Participants | Participants | Up to 66 months |
|
| ||||||||||||||||||||||||||||
| Secondary | Duration of Response | From the onset of temozolomide to the date at which unequivocal disease progression, assessed up to 65 months. | Reduction in number of patients assessed relative to total patients enrolled is due to some patient's disease progressing prior to start of temozolomide. | Posted | Median | Full Range | months | Up to 65 months |
|
| ||||||||||||||||||||||||||
| Secondary | Time to Progression | From the first day of treatment (transplant) until unequivocal progression is documented, assessed up to 66 months. | Reduction in number of patients assessed relative to total patients enrolled is due to some patient's disease progressing prior to start of temozolomide. | Posted | Median | Full Range | months | Up to 66 months. |
|
| ||||||||||||||||||||||||||
| Secondary | Number of Participants That Survived | From the first day of treatment until death, assessed up to 74 months. | Posted | Count of Participants | Participants | Up to 74 months |
|
| ||||||||||||||||||||||||||||
| Secondary | Number of Participants With Chemoprotection | assessed by the ability to increase the Temozolomide dose beyond 472 mg/m^2 | Posted | Count of Participants | Participants | Up to 66 months |
|
| ||||||||||||||||||||||||||||
| Secondary | Number of Participants With Chemoselection | assessed by the increase in peripheral blood Vector Copy Number (VCN), the average copies of integrated transgene per cell, after chemotherapy | Posted | Count of Participants | Participants | Up to 59 months |
|
| ||||||||||||||||||||||||||||
| Secondary | Gene Transfer Efficiency | 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. | Posted | Mean | Standard Error | copies/cell | Up to 59 months |
|
| |||||||||||||||||||||||||||
| Secondary | Gene Transfer Efficiency After Chemotherapy | 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. | Posted | Mean | Standard Error | copies/cell | Up to 59 months |
|
|
Serious and other Adverse Events are collected through study completion, on average 2 years. All cause mortality was assessed up to 7 years.
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 | 11 | 11 | 0 | 11 | 11 | 11 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardiovascular | Cardiac disorders | Systematic Assessment |
| ||
| Digestive | Gastrointestinal disorders | Systematic Assessment |
| ||
| Endocrine | Endocrine disorders | Systematic Assessment |
| ||
| General | General disorders | Systematic Assessment |
| ||
| HEENT | Ear and labyrinth disorders | Systematic Assessment |
| ||
| Heme & Lymphatics | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Metabolic & Nutritional | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Musculoskeletal | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Nervous | Nervous system disorders | Systematic Assessment |
| ||
| Respiratory | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Skin & Appendages | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Urogenital | Reproductive system and breast disorders | Systematic Assessment |
|
Not provided
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Hans-Peter Kiem, M.D., Ph.D. | Fred Hutch Cancer Research Center | 206.667.4425 | hkiem@fredhutch.org |
| Nov 6, 2018 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D005909 | Glioblastoma |
| D018316 | Gliosarcoma |
| ID | Term |
|---|---|
| D001254 | Astrocytoma |
| D005910 | Glioma |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
Not provided
Not provided
| ID | Term |
|---|---|
| D020266 | Radiotherapy, Conformal |
| D002330 | Carmustine |
| C574855 | carmustine, poliferprosan 20 drug combination |
| D000069585 | Filgrastim |
| D016179 | Granulocyte Colony-Stimulating Factor |
| D050397 | Radiotherapy, Intensity-Modulated |
| C064976 | O(6)-benzylguanine |
| C088327 | plerixafor |
| C049051 | ferric pyrophosphate |
| D061766 | Proton Therapy |
| D000077204 | Temozolomide |
| ID | Term |
|---|---|
| D011881 | Radiotherapy, Computer-Assisted |
| D011878 | Radiotherapy |
| D013812 | Therapeutics |
| D009607 | Nitrosourea Compounds |
| D014508 | Urea |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D009603 | Nitroso Compounds |
| D003115 | Colony-Stimulating Factors |
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D016298 | Hematopoietic Cell Growth Factors |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011506 | Proteins |
| D001685 | Biological Factors |
| D063193 | Heavy Ion Radiotherapy |
| D003606 | Dacarbazine |
| D014226 | Triazenes |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
|
|
|
|
|
|
|
|