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Report for Clinical Trial NCT00669669

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

Benzylguanine-Mediated Tumor Sensitization With Chemoprotected Autologous Stem Cells for Patients With Malignant Gliomas

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.

NCT00669669 Glioblastoma Gliosarcoma
MeSH: Glioblastoma Glioma Gliosarcoma
HPO: Glioblastoma multiforme Glioma

11 Interventions

Name: 3-Dimensional Conformal Radiation Therapy

Description: Undergo 3D conformal IMRT

Type: Radiation

Treatment (chemotherapy, autologous stem cell transplant)

Name: Autologous Hematopoietic Stem Cell Transplantation

Description: Undergo autologous in vitro-treated peripheral blood stem cell transplant

Type: Procedure

Treatment (chemotherapy, autologous stem cell transplant)

Name: Carmustine

Description: Given IV

Type: Drug

Treatment (chemotherapy, autologous stem cell transplant)

Name: Filgrastim

Description: Given SC

Type: Biological

Treatment (chemotherapy, autologous stem cell transplant)

Name: In Vitro-Treated Peripheral Blood Stem Cell Transplantation

Description: Undergo autologous in vitro-treated peripheral blood stem cell transplant

Type: Procedure

Treatment (chemotherapy, autologous stem cell transplant)

Name: Intensity-Modulated Radiation Therapy

Description: Undergo 3D conformal IMRT

Type: Radiation

Treatment (chemotherapy, autologous stem cell transplant)

Name: Laboratory Biomarker Analysis

Description: Correlative studies

Type: Other

Treatment (chemotherapy, autologous stem cell transplant)

Name: O6-Benzylguanine

Description: Given IV

Type: Drug

Treatment (chemotherapy, autologous stem cell transplant)

Name: Plerixafor

Description: Given SC

Type: Drug

Treatment (chemotherapy, autologous stem cell transplant)

Name: Proton Beam Radiation Therapy

Description: Undergo proton beam radiation therapy

Type: Radiation

Treatment (chemotherapy, autologous stem cell transplant)

Name: Temozolomide

Description: Given PO

Type: Drug

Treatment (chemotherapy, autologous stem cell transplant)


Primary Outcomes

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

Measure: Number of Participants Dose-limiting Toxicity (DLT)

Time: Up to 6 weeks after infusion

Description: Replication competent retrovirus or diagnosis of leukemia

Measure: Number of Participants With Retrovirus or Leukemia

Time: Up to 2 years after infusion

Secondary Outcomes

Description: Proportion of patients with reduction in tumor burden of a predefined amount

Measure: Response Rate

Time: Up to 15 years

Description: From the onset of temozolomide to the date at which unequivocal disease progression, assessed up to 15 years

Measure: Duration of Response

Time: Up to 15 years

Description: From the first day of treatment until death, assessed up to 15 years

Measure: Number of Participants That Survived

Time: Up to 15 years

Description: From the first day of treatment until unequivocal progression is documented, assessed up to 15 years

Measure: Time to Progression

Time: Up to 15 years

Description: Assessed by gene marking in peripheral blood and marrow

Measure: Gene Transfer Efficiency and in Vivo Selection

Time: Up to 15 years

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

Measure: Number of Participants With Chemoprotection

Time: Up to 15 years

Purpose: Treatment

Single Group Assignment


There is one SNP

SNPs


1 P140K

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 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 Glioblastoma Gliosarcoma Glioblastoma Glioma Gliosarcoma 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). --- P140K ---

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



HPO Nodes


HPO:
Glioblastoma multiforme
Genes 23
FAN1 APC BMPR1A KRAS BRCA2 RPS20 MLH1 MSH2 MSH6 EPCAM PMS2 MLH1 MLH3 PMS2 PMS1 MSH6 TP53 MSH2 TGFBR2 PIK3CA SEMA4A ERBB2 IDH1
Glioma
Genes 50
TSC2 GLI3 BRCA2 TSC1 LRP5 MLH1 PMS2 APC IDH1 MSH6 POT1 TSC2 CDKN2A NF2 MSH3 MSH6 APC NF1 EPCAM TSC1 TGFBR2 SEMA4A IDH1 IDH2 FAN1 APC MSH3 BMPR1A KRAS MLH1 MSH2 C11ORF95 PMS2 MLH3 PIK3CA NBN RELA SETBP1 IFNG RPS20 NF1 PMS1 CHEK2 APC TP53 MSH2 NBN ERBB2 APC NF2