A Phase I Study of the Chemoprotectant Amifostine With Autologous Stem Cell Transplantation for High Risk or Relapsed Pediatric Solid Tumors and Brain Tumors
- Determine the dose-limiting toxicity of amifostine chemoprotection with peripheral
blood stem cell transplantation plus chemotherapy in patients with high-risk or
relapsed solid tumors or brain tumors.
- Determine response or time to disease progression in patients treated with this
OUTLINE: This is a dose-escalation study of amifostine. Patients are stratified according to
age (1 to 18 vs 19 to 45 years).
All patients receive filgrastim (G-CSF) IV for 1 week. On day 6 of G-CSF administration,
patients undergo peripheral blood stem cell (PBSC) harvest followed by chemotherapy.
Patients receive oral busulfan every 6 hours on days -8 to -6 followed by melphalan IV over
30 minutes on days -5 and -4 and thiotepa IV over 2 hours on days -3 and -2. Patients
receive amifostine IV over 5 minutes beginning 30 minutes prior to melphalan and thiotepa
administration on days -5 to -1. PBSC are reinfused on day 0.
Cohorts of 3-6 patients receive escalating doses of amifostine until the maximum tolerated
dose 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 on day 50; at 3, 6, and 9 months; and at 1, 2, and 3 years post PBSC
PROJECTED ACCRUAL: A maximum of 60 patients (30 per stratum) will be accrued for this study
within 3 years.
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Supportive Care
John P. Perentesis, MD
Masonic Cancer Center, University of Minnesota
United States: Food and Drug Administration
|University of Minnesota Cancer Center||Minneapolis, Minnesota 55455|