Benzylguanine-Mediated Tumor Sensitization With Chemoprotected Autologous Stem Cells for Patients With Malignant Gliomas
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Number of Participants Dose-limiting Toxicity (DLT)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Treatment (chemotherapy, autologous stem cell transplant)
See Detailed Description
干预措施: 3-Dimensional Conformal Radiation Therapy (Radiation)
Treatment (chemotherapy, autologous stem cell transplant)
See Detailed Description
干预措施: Autologous Hematopoietic Stem Cell Transplantation (Procedure)
Treatment (chemotherapy, autologous stem cell transplant)
See Detailed Description
干预措施: Carmustine (Drug)
Treatment (chemotherapy, autologous stem cell transplant)
See Detailed Description
干预措施: Filgrastim (Biological)
Treatment (chemotherapy, autologous stem cell transplant)
See Detailed Description
干预措施: In Vitro-Treated Peripheral Blood Stem Cell Transplantation (Procedure)
Treatment (chemotherapy, autologous stem cell transplant)
See Detailed Description
干预措施: Intensity-Modulated Radiation Therapy (Radiation)
Treatment (chemotherapy, autologous stem cell transplant)
See Detailed Description
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (chemotherapy, autologous stem cell transplant)
See Detailed Description
干预措施: O6-Benzylguanine (Drug)
Treatment (chemotherapy, autologous stem cell transplant)
See Detailed Description
干预措施: Plerixafor (Drug)
Treatment (chemotherapy, autologous stem cell transplant)
See Detailed Description
干预措施: Proton Beam Radiation Therapy (Radiation)
Treatment (chemotherapy, autologous stem cell transplant)
See Detailed Description
干预措施: Temozolomide (Drug)
结局指标
主要结局
Number of Participants Dose-limiting Toxicity (DLT)
时间窗: 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
时间窗: Up to 2 years after infusion
Replication competent retrovirus or diagnosis of leukemia
次要结局
- Response Rate(Up to 66 months)
- Number of Participants That Survived(Up to 74 months)
- Number of Participants With Chemoprotection(Up to 66 months)
- Time to Progression(Up to 66 months.)
- Number of Participants With Chemoselection(Up to 59 months)
- Duration of Response(Up to 65 months)
- Gene Transfer Efficiency(Up to 59 months)
- Gene Transfer Efficiency After Chemotherapy(Up to 59 months)