A Phase I Study of the Chemoprotectant Amifostine With Autologous Stem Cell Transplantation for High Risk or Relapsed Pediatric Solid Tumors and Brain Tumors
A Phase I Study of the Chemoprotectant Amifostine With Autologous Stem Cell Transplantation for High Risk or Relapsed Pediatric Solid Tumors and Brain Tumors
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Chemoprotective drugs such as amifostine may protect normal cells from the side effects of high-dose chemotherapy.
PURPOSE: Phase I trial to study the effectiveness of amifostine in protecting from the side effects of peripheral stem cell transplantation in treating patients who have high-risk or relapsed solid tumors.
OBJECTIVES:
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 transplantation.
PROJECTED ACCRUAL: A maximum of 60 patients (30 per stratum) will be accrued for this study within 3 years.
Inclusion Criteria:
Histologically confirmed high-risk or relapsed solid tumors or brain tumors, including:
Patients receive peripheral blood stem cell transplantation only if in complete remission or in very good partial remission with no disease progression
Must have radiologic, nuclear image, or histologic verification of relapse
Age 1 to 45
Performance status:Karnofsky 70-100%
Absolute neutrophil count greater than 1,000/mm^3
Platelet count greater than 100,000/mm^3
Hemoglobin count at least 10 g/dL
Bilirubin less than 2 times upper limit of normal (ULN)
SGOT or SGPT less than 2.5 times ULN
Creatinine less than 2 times ULN
Creatinine clearance greater than 70 mL/min
Cardiac shortening fraction greater than 30%
Cardiac ejection fraction greater than 45%
At least 1 week since prior hematopoietic growth factor and recovered
At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered
Recovered from any prior therapy
Exclusion Criteria: