ClinicalTrials.gg
Sign In
CompletedNCT00004853Updated Nov 12, 2019

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

A Phase 1 interventional study of Filgrastim and Filgrastim-SD/01 in Ewing's Sarcoma, Rhabdomyosarcoma and MPNST, sponsored by National Cancer Institute (NCI). Completed at 1 site in United States. Open to participants aged Up to 25 Years. Per ClinicalTrials.gov, last updated 2019-11-12.

Sponsored by National Cancer Institute (NCI) · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
34
Allocation
Randomized
Ages
Up to 25 Years
Sex
All
01

Study 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.

Read the 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.
02

Conditions studied

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

Keywords

  • AMGEN
  • Granulocyte Colony-Stimulating Factor
  • MPNST
  • Randomized
  • Sarcoma
  • Tumor
03

In context

Sarcoma, Ewing

290 studies on the registry are indexed under Sarcoma, Ewing; 67 are open to participants now.

This study's enrollment of 34 is below the median of 39 across 228 interventional studies indexed under Sarcoma, Ewing.

Browse Sarcoma, Ewing studies →

Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,554 studies on the registry; 334 are open to participants now.

Of its 407 completed or terminated interventional studies of FDA-regulated products, 370 (91%) have results posted.

Browse National Cancer Institute (NCI) studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
Up to 25 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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.
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
34 participants (actual)

Study arms

  • Experimental
    1

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

    Biological: Filgrastim

  • Experimental
    2

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

    Biological: Filgrastim-SD/01

Interventions

  • BiologicalFilgrastim

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

  • BiologicalFilgrastim-SD/01

    Drug page: Pegfilgrastim

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

06

What researchers measure

Primary outcomes

  1. Tolerance and toxicity

    Time frame: 1 year

  2. PKs

    Time frame: 1 year

Secondary outcomes

  1. Compare neutrophil function

  2. Compare CD34 positive stem cell mobilization

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

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

  5. Assess methods of detecting minimal residual disease

  6. cDNA microarray analysis of gene expression, development of cell lines and xenotransplantation models, and exploration of apoptotic pathways

07

Study locations

1 site
  • National Institutes of Health Clinical Center, 9000 Rockville Pike
    Bethesda, Maryland 20892, United States
08

References and documents

Publications

  • 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. PubMed 1458545 ↗
  • 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. PubMed 8822908 ↗
  • 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. PubMed 2475185 ↗
09

Timeline

Tracking since Sep 25, 2026
Not marked actual or estimatedDates not marked actual or estimated

The record gives a start of Mar 2000, a primary completion of May 2009 and a completion of May 2009. It does not say whether these dates are actual or estimated.

How these figures are worked out, and which studies are left out of them.

Registered
Mar 4, 2000
First posted
Mar 6, 2000
Start
Mar 3, 2000
Primary completionActual
May 20, 2009
CompletionActual
May 20, 2009
Last update
Nov 12, 2019
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Nov 12, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT00004853
Lead sponsor
National Cancer Institute (NCI)
First posted
Mar 6, 2000
Start date
Mar 3, 2000
Primary completion
May 20, 2009
Completion
May 20, 2009
Last update
Nov 12, 2019

Study contacts

Crystal L Mackall, M.D.
principal investigator · National Cancer Institute (NCI)
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jan 2016. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Studies of the drugs tested here: Filgrastim · Pegfilgrastim

Other studies in this condition

Sarcoma, Ewing →

Other studies from this sponsor

National Cancer Institute (NCI) →

Start the discussion