Dose Escalation of Temozolomide in Combination With Thiotepa and Carboplatin With Autologous Stem Cell Rescue in Patients With Malignant Brain Tumors With Minimal Residual Disease
- Determine the maximum tolerated dose of temozolomide in combination with thiotepa and
carboplatin followed by autologous peripheral blood stem cell or bone marrow
transplantation in patients with recurrent high-grade brain tumors with minimal
residual disease or newly-diagnosed malignant glioma with minimal residual disease
OUTLINE: This is a dose-escalation study of temozolomide.
Patients receive filgrastim (G-CSF) subcutaneously (SC) once daily for 3 consecutive days.
After the third dose of G-CSF, patients undergo leukapheresis to collect peripheral blood
stem cells (PBSC). Patients who do not have adequate PBSC may undergo bone marrow harvest.
Patients then receive oral temozolomide every 12 hours on days -10 to -6 and thiotepa IV
over 3 hours and carboplatin IV over 4 hours on days -5 to -3.
PBSC or bone marrow are reinfused on day 0. Beginning on day 1, patients receive G-CSF SC or
IV until blood counts recover.
Cohorts of 3-6 patients receive escalating doses of temozolomide until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
of 6 patients experience dose-limiting toxicity.
Patients are followed at day 42, at 3 months, every 3 months for 2 years, every 4 months for
1 year, every 6 months for 1 year, and then annually thereafter.
PROJECTED ACCRUAL: A total of 18-30 patients will be accrued for this study.
Primary Purpose: Treatment
Sharon L. Gardner, MD
New York University School of Medicine
United States: Federal Government
|Children's Hospital of Philadelphia||Philadelphia, Pennsylvania 19104|
|NYU Cancer Institute at New York University Medical Center||New York, New York 10016|
|Columbus Children's Hospital||Columbus, Ohio 43205-2696|