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

NCT ID: NCT00004853

Last Updated: 2019-11-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-03-03
• Study Completion Date: 2009-05-20

Brief Summary

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. Supportive care measures used in children who are treated with this regimen include mesna to prevent oxazaphosphorine urotoxicity, dexrazoxane to reduce doxorubicin cardiotoxicity, and filgrastim to shorten the duration of neutropenia. The purpose of this randomized open label trial is to 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. 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 and for detailed cardiac studies. High-risk patients who are treated on this front line trial and respond will also be candidates for a planned transplant protocol. A total of 34 patients (17 patients per treatment arm) will be entered onto the trial.

Detailed Description

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.

Conditions

Ewing's Sarcoma; Rhabdomyosarcoma; MPNST; Synovial Sarcoma; High-risk Sarcoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

single dose of intervention after each cycle of Standard 5 drug dose-intensive chemotherapy

Group Type: EXPERIMENTAL

Filgrastim

Intervention Type: BIOLOGICAL

5 microgram/kg/dose SC daily starting 24-36 hours after last dose of chemotherapy until post-nadir ANC \>=10,000/microliter

2

single dose of interventionafter each cycle of Standard 5 drug dose-intensive chemotherapy

Group Type: EXPERIMENTAL

Filgrastim-SD/01

Intervention Type: BIOLOGICAL

100 microgram/kg SC 24-36 hours after last dose of chemotherapy (single dose)

Interventions

Filgrastim

5 microgram/kg/dose SC daily starting 24-36 hours after last dose of chemotherapy until post-nadir ANC \>=10,000/microliter

Intervention Type: BIOLOGICAL

Filgrastim-SD/01

100 microgram/kg SC 24-36 hours after last dose of chemotherapy (single dose)

Intervention Type: BIOLOGICAL

Eligibility Criteria

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.

• Maximum Eligible Age: 25 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Principal Investigators

Crystal L Mackall, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Cancer Institute (NCI)

Locations

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, United States

Countries

United States

References

Delgado C, Francis GE, Fisher D. The uses and properties of PEG-linked proteins. Crit Rev Ther Drug Carrier Syst. 1992;9(3-4):249-304.

Reference Type: BACKGROUND

PMID: 1458545 (View on PubMed)

Welte K, Gabrilove J, Bronchud MH, Platzer E, Morstyn G. Filgrastim (r-metHuG-CSF): the first 10 years. Blood. 1996 Sep 15;88(6):1907-29. No abstract available.

Reference Type: BACKGROUND

PMID: 8822908 (View on PubMed)

Layton JE, Hockman H, Sheridan WP, Morstyn G. Evidence for a novel in vivo control mechanism of granulopoiesis: mature cell-related control of a regulatory growth factor. Blood. 1989 Sep;74(4):1303-7.

Reference Type: BACKGROUND

PMID: 2475185 (View on PubMed)

Other Identifiers

00-C-0092

Identifier Type: -

Identifier Source: secondary_id

000092

Identifier Type: -

Identifier Source: org_study_id

NCT00020137

Identifier Type: -

Identifier Source: nct_alias