Comparison of Filgrastim and Filgrastim SD/01in Boosting White Cell Counts After 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.

• INCLUSION CRITERIA:
• Newly diagnosed histologically proven:

• Ewing's sarcoma family of tumors, including peripheral neuroectodermal tumors;
• Alveolar rhabdomyosarcoma;
• Stage 3 or 4 embryonal rhabdomyosarcoma;
• Malignant peripheral nerve sheath tumor that is unresectable, incompletely resected with bulk residual disease or metastatic;
• Synovial cell sarcoma that is unresectable, incompletely resected with bulk residual disease, or metastatic.
• Age equal to or less than 25 years at the time of diagnosis.
• Normal cardiac function (ejection fraction by MUGA or ECHO that is within the institutional normal range).
• Normal serum creatinine for age or creatinine clearance greater than 60 ml/min/1.73m(2).
• Normal liver function (SGPT less than 5 times the upper limit of normal and bilirubin less than 2.5 times the upper limit of normal).
• Normal hematologic function (absolute neutrophil count equal to or greater than 1500/microL, hemoglobin equal to or greater than 9.0 g/dl and platelet count equal to or greater than 100,000/microL).
• Subjects of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study.

Exclusion criteria

• Previous chemotherapy or radiotherapy.
• Pregnant or breast feeding females because the chemotherapy administered on this trial could have a detrimental effect on the developing fetus or newborn.
• Histological evidence of tumor infiltration of bone marrow.
• Stage 1 or 2 embryonal rhabdomyosarcomas.