A Pilot Study of Temozolomide and O-Benzylguanine for Treatment of High-Grade Glioma, Using Autologous Peripheral Blood Stem Cells Genetically Modified for Chemoprotection
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
Study Overview
Brief Summary
RATIONALE: Drugs used in chemotherapy, such as temozolomide, busulfan, and O6-benzylguanine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. O6-benzylguanine may also help temozolomide work better by making tumor cells more sensitive to the drug. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving chemotherapy with a peripheral stem cell transplant or bone marrow transplant, using stem cells from the patient that are genetically-modified in the laboratory to protect them from the side effects of chemotherapy, may allow more chemotherapy to be given so that more tumor cells are killed. Giving combination chemotherapy and radiation therapy together with a peripheral stem cell transplant or bone marrow transplant may kill more tumor cells.
PURPOSE: This clinical trial is studying how well giving combination chemotherapy together with radiation therapy works in treating younger patients who are undergoing an autologous stem cell transplant for newly diagnosed gliomas.
Detailed Description
OBJECTIVES:
Primary
- Determine the safety and feasibility of a conditioning regimen comprising temozolomide, radiotherapy, and busulfan followed by an infusion of autologous stem cells genetically modified with the MGMT gene and temozolomide and O6-benzylguanine in younger patients with newly diagnosed high-grade gliomas.
Secondary
- Determine the tolerability of intrapatient dose escalation of temozolomide, in terms of transgene expression, in patients treated with this regimen.
- Determine, preliminarily, the antitumor activity of this regimen in these patients.
Study Design
- Study Type
- Interventional
- Primary Purpose
- Treatment
Eligibility Criteria
- Ages
- 5 Years to 55 Years (Child, Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed newly diagnosed high-grade glioma of 1 of the following types:
- •Glioblastoma multiforme
- •WHO grade IV disease
- •Anaplastic astrocytoma
- •WHO grade III disease
- •No low-grade disease (i.e., WHO grade I-II disease)
- •No WHO grade III oligodendroglioma or oligoastrocytoma
- •Patients > 30 years of age who have undergone a gross total resection and have nonmeasurable disease as seen on postoperative MRI are eligible
- •Measurable disease, as assessed by postoperative MRI, is required in patients ≤ 30 years of age
- •No tumor arising in the spine or brainstem
- •No metastatic disease in the spine
- •PATIENT CHARACTERISTICS:
- •Performance status
- •Karnofsky 50-100% (for patients 11-30 years of age) OR
- •Lansky 50-100% (for patients 5-10 years of age)
- •Life expectancy
- •At least 9 months
- •Hematopoietic
- •Absolute neutrophil count ≥ 1,000/mm^3
- •Platelet count ≥ 75,000/mm^3 (transfusion independent)
- •Bilirubin ≤ 2.0 mg/dL
- •ALT and AST ≤ 2.5 times upper limit of normal
- •Albumin ≥ 2.0 g/dL
- •Hepatitis B surface antigen and core antibody negative
- •Hepatitis C antibody negative
- •Creatinine normal OR
- •Glomerular filtration rate ≥ 70 mL/min
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •Neurologic deficits must be stable or decreasing
- •No active infection
- •HIV negative
- •No other serious illness or medical condition that would preclude study participation
- •PRIOR CONCURRENT THERAPY:
- •Chemotherapy
- •No prior chemotherapy
- •Endocrine therapy
- •Concurrent corticosteroids allowed provided dose is stable or decreasing
- •Radiotherapy
- •No prior radiotherapy
- •See Disease Characteristics
- •No other concurrent investigational anticancer agents
Exclusion Criteria
- Not provided