A Randomized Trial of Filgrastim-SD/01 vs. Filgrastim in Newly Diagnosed Children and Young Adults With Sarcoma Treated With Dose-Intensive Chemotherapy

Background: Filgrastim (granulocyte colony-stimulating factor), which is administered by daily subcutaneous injection after cytotoxic chemotherapy, shortens the duration of chemotherapy-induced neutropenia and lowers the risk of infection. In children treated with dose-intensive chemotherapy, Filgrastim reduces the duration of severe neutropenia and, as a result, has become a standard component of the treatment regimen. Filgrastim-SD/01 (AMGEN), which is produced by PEGylation of the amino-terminus of Filgrastim, is a sustained duration form of granulocyte colony-stimulating factor. In phase I and phase II trials in adults, a single dose of Filgrastim-SD/01 appears to be equivalent to daily dosing of Filgrastim in enhancing neutrophil recovery and has a comparable adverse event profile. Dose-intensive vincristine/cyclophosphamide/doxorubicin (VDoxC) alternating with ifosfamide/etoposide (IE) has become standard therapy for children and adolescents with Ewing's sarcoma and other sarcomas treated at the POB/NCI and other cancer centers within the US. Objectives: Compare the tolerance, toxicity, and therapeutic effects of Filgrastim-SD/01 given as a single injection after chemotherapy to daily subcutaneous Filgrastim in patients with newly diagnosed sarcoma receiving multi-agent, dose intensive chemotherapy. The pharmacokinetics of Filgrastim-SD/01 will also be compared to the pharmacokinetics of Filgrastim. This trial will also be a platform for performing biological studies of these tumors study neutrophil function and CD34 mobilization, and for detailed cardiac studies. Eligibility: Children and young adults (less than or equal to 25 years) with previously untreated high-risk sarcomas (Ewing sarcoma, rhabdomyosarcoma, MPNST, and synovial sarcoma). No evidence of tumor infiltration of the bone marrow. Design: Participants will be randomized (1:1) to receive a single dose of Filgrastim-SD/01 or daily filgrastim as a SQ injection after each cycle of chemotherapy. Standard 5 drug dose-intensive chemotherapy with vincristine, doxorubicin, cyclophosphamide alternating with ifosfamide and etoposide will be administered. Surgery or radiation for the primary tumor will occur after cycle 5. A total of 34 patients (17 patients per treatment arm) will be entered onto the trial.