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

NCT00004853 | Completed Phase 1

• 2 other identifiers: 00009200-C-0092
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

AMGEN; Granulocyte Colony-Stimulating Factor; MPNST; Randomized; Sarcoma; Tumor

Outcome Measures

Primary Outcomes (2)

• Tolerance and toxicity

  1 year

• PKs

  1 year

Secondary Outcomes (6)

• Compare neutrophil function

• Compare CD34 positive stem cell mobilization

• Compare days of febrile neutropenia, days on antibiotics, and inpatient days resulting from neutropenia

• Evaluate the role of functional cardiac MRI and serum troponin T levels in detecting early doxorubicin cardiotoxicity

• Assess methods of detecting minimal residual disease

Study Arms (2)

1

EXPERIMENTAL

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

Biological: Filgrastim

2

EXPERIMENTAL

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

Biological: Filgrastim-SD/01

Interventions

Filgrastim BIOLOGICAL

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

1

Filgrastim-SD/01 BIOLOGICAL

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

2

Eligibility Criteria

• Age: Up to 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• 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.

  PMID: 1458545 BACKGROUND

• 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.

  PMID: 8822908 BACKGROUND

• 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.

  PMID: 2475185 BACKGROUND

MeSH Terms

Conditions

Sarcoma, Ewing; Rhabdomyosarcoma; Neurofibrosarcoma; Sarcoma, Synovial; Sarcoma; Neoplasms

Interventions

Filgrastim; pegfilgrastim

Condition Hierarchy (Ancestors)

Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Myosarcoma; Neoplasms, Muscle Tissue; Fibrosarcoma; Neoplasms, Fibrous Tissue; Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Peripheral Nervous System Neoplasms; Nervous System Neoplasms; Nervous System Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases

Intervention Hierarchy (Ancestors)

Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Crystal L Mackall, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH

Study Record Dates

• First Submitted: March 4, 2000
• First Posted: March 6, 2000
• Study Start: March 3, 2000
• Primary Completion: May 20, 2009
• Study Completion: May 20, 2009
• Last Updated: November 12, 2019

Record last verified: 2016-01-27

Locations

US (1)