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.