Study of Fixed vs. Flexible Filgrastim to Accelerate Bone Marrow Recovery After Chemotherapy in Children With Cancer

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified June 2014 by Barbara Ann Karmanos Cancer Institute
Sponsor:
Collaborators:
Children's Hospital of Michigan
Information provided by (Responsible Party):
Maxim Yankelevich, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier:
NCT01987596
First received: November 12, 2013
Last updated: June 21, 2014
Last verified: June 2014
  Purpose

This randomized phase III trial studies flexible administration of filgrastim after combination chemotherapy to see how well it works compared to fixed administration of filgrastim in decreasing side effects of chemotherapy in younger patients with cancer. Cancer chemotherapy frequently results in neutropenia (low blood counts) when patients are susceptible to severe infections. A medicine called G-CSF (filgrastim) stimulates bone marrow and daily filgrastim shots are commonly used to shorten neutropenic periods and decrease infections after chemotherapy. Since filgrastim is customarily used on a fixed schedule starting early after chemotherapy and there are data that early doses may not be needed, this study tests new flexible schedule of filgrastim to optimize its use by reducing the number of painful shots, cost of treatment, and filgrastim side effects in children with cancer receiving chemotherapy.


Condition Intervention Phase
Childhood Central Nervous System Choriocarcinoma
Childhood Central Nervous System Germinoma
Childhood Central Nervous System Mixed Germ Cell Tumor
Childhood Central Nervous System Teratoma
Childhood Central Nervous System Yolk Sac Tumor
Childhood Choroid Plexus Tumor
Childhood Craniopharyngioma
Childhood Ependymoblastoma
Childhood Extracranial Germ Cell Tumor
Childhood Grade I Meningioma
Childhood Grade II Meningioma
Childhood Grade III Meningioma
Childhood High-grade Cerebellar Astrocytoma
Childhood High-grade Cerebral Astrocytoma
Childhood Infratentorial Ependymoma
Childhood Low-grade Cerebellar Astrocytoma
Childhood Low-grade Cerebral Astrocytoma
Childhood Malignant Ovarian Germ Cell Tumor
Childhood Malignant Testicular Germ Cell Tumor
Childhood Medulloepithelioma
Childhood Supratentorial Ependymoma
Childhood Teratoma
Recurrent Childhood Anaplastic Astrocytoma
Recurrent Childhood Anaplastic Oligoastrocytoma
Recurrent Childhood Anaplastic Oligodendroglioma
Recurrent Childhood Brain Stem Glioma
Recurrent Childhood Central Nervous System Embryonal Tumor
Recurrent Childhood Cerebellar Astrocytoma
Recurrent Childhood Cerebral Astrocytoma
Recurrent Childhood Diffuse Astrocytoma
Recurrent Childhood Ependymoma
Recurrent Childhood Fibrillary Astrocytoma
Recurrent Childhood Gemistocytic Astrocytoma
Recurrent Childhood Giant Cell Glioblastoma
Recurrent Childhood Glioblastoma
Recurrent Childhood Gliomatosis Cerebri
Recurrent Childhood Gliosarcoma
Recurrent Childhood Malignant Germ Cell Tumor
Recurrent Childhood Medulloblastoma
Recurrent Childhood Oligoastrocytoma
Recurrent Childhood Oligodendroglioma
Recurrent Childhood Pilocytic Astrocytoma
Recurrent Childhood Pilomyxoid Astrocytoma
Recurrent Childhood Pineoblastoma
Recurrent Childhood Pleomorphic Xanthoastrocytoma
Recurrent Childhood Protoplasmic Astrocytoma
Recurrent Childhood Soft Tissue Sarcoma
Recurrent Childhood Subependymal Giant Cell Astrocytoma
Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor
Recurrent Childhood Visual Pathway and Hypothalamic Glioma
Recurrent Childhood Visual Pathway Glioma
Recurrent Neuroblastoma
Recurrent Osteosarcoma
Recurrent Retinoblastoma
Recurrent Wilms Tumor and Other Childhood Kidney Tumors
Recurrent/Refractory Childhood Hodgkin Lymphoma
Unspecified Childhood Solid Tumor, Protocol Specific
Drug: etoposide
Drug: ifosfamide
Drug: carboplatin
Drug: topotecan hydrochloride
Drug: vincristine sulfate
Drug: cyclophosphamide
Drug: cisplatin
Biological: filgrastim
Other: laboratory biomarker analysis
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Supportive Care
Official Title: Prospective and Randomized Study of Fixed Versus Flexible Prophylactic Administration of Granulocyte Colony-Stimulating Factor (G-CSF) in Children With Cancer

Resource links provided by NLM:

Genetic and Rare Diseases Information Center resources: Glioma Lymphosarcoma Hodgkin Lymphoma Kidney Cancer Renal Cancer Glioblastoma Children's Interstitial Lung Disease Anaplastic Astrocytoma Neuroblastoma Soft Tissue Sarcoma Malignant Mesenchymal Tumor Ependymoma Osteosarcoma Bone Cancer Neuroepithelioma Medulloblastoma Supratentorial Primitive Neuroectodermal Tumor Medulloblastoma, Childhood Cerebellar Astrocytoma, Childhood Pineoblastoma, Childhood Supratentorial Primitive Neuroectodermal Tumors, Childhood Cerebral Astrocytoma, Childhood Malignant Germ Cell Tumor Oligodendroglioma Anaplastic Oligodendroglioma Craniopharyngioma Oligoastrocytoma Anaplastic Oligoastrocytoma Ovarian Germ Cell Tumor Testicular Cancer Wilms' Tumor Retinoblastoma Gliosarcoma Meningioma Brain Stem Glioma, Childhood Diffuse Astrocytoma Hodgkin Lymphoma, Childhood Pilocytic Astrocytoma Optic Pathway Glioma Subependymal Giant Cell Astrocytoma Pineoblastoma Embryonal Tumor With Multilayered Rosettes Choriocarcinoma Yolk Sac Tumor Extracranial Germ Cell Tumor, Childhood Gliomatosis Cerebri Pleomorphic Xanthoastrocytoma Ovarian Cancer Gestational Trophoblastic Tumor Hydatidiform Mole
U.S. FDA Resources

Further study details as provided by Barbara Ann Karmanos Cancer Institute:

Primary Outcome Measures:
  • Duration (days) of ANC less than 500/uL [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    General linear model (GLM) procedure will be performed to examine differences between groups.

  • Days to ANC greater than or equal to 1,000/uL from the start of chemotherapy [ Time Frame: From the start of the course until the first date the ANC reaches >= 1,000/uL post nadir, assessed up to 1 year ] [ Designated as safety issue: No ]
    The analysis will be reported by displaying mean values (for each treatment in each sequence) as well as their differences, and 95% confidence intervals for the mean difference between treatments (adjusting for the period effect). Kaplan-Meier approach will be used.

  • Days to transfusion unsupported platelet count greater than or equal to 75,000/uL from the start of chemotherapy [ Time Frame: From the start of the course until the first date the platelet count reaches >= 75,000/uL without platelet transfusion support, assessed up to 1 year ] [ Designated as safety issue: No ]
    Kaplan-Meier approach will be used.


Secondary Outcome Measures:
  • Incidence of febrile neutropenia [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Categorically scaled variables will be presented as numbers, ratios, and percentages. The McNemar's test will be used to assess the statistical significance of categorical data.

  • Incidence of hospitalization [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Categorically scaled variables will be presented as numbers, ratios, and percentages. The McNemar's test will be used to assess the statistical significance of categorical data.

  • Number of platelet transfusions per chemotherapy cycle [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    GLM procedure will be performed to examine differences between groups.

  • Days of filgrastim administration [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    GLM procedure will be performed to examine differences between groups.

  • Incidence of filgrastim related pain [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Categorically scaled variables will be presented as numbers, ratios, and percentages. The McNemar's test will be used to assess the statistical significance of categorical data.

  • Duration of filgrastim related pain [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Univariately, continuously scaled variables will be presented as means, standard deviations, medians, ranges, and interquartile ranges.

  • Incidence of bacteremia [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Categorically scaled variables will be presented as numbers, ratios, and percentages. The McNemar's test will be used to assess the statistical significance of categorical data.

  • Percentage of progenitor cells in peripheral blood [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    GLM procedure will be performed to examine differences between groups.


Estimated Enrollment: 30
Study Start Date: June 2014
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (fixed filgrastim)
Patients receive filgrastim SC QD started at 24 hours after completion of chemotherapy and stopped when ANC reaches at least 2,000/uL post nadir.
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: ifosfamide
Given IV
Other Names:
  • Cyfos
  • Holoxan
  • IFF
  • IFX
  • IPP
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Drug: topotecan hydrochloride
Given IV
Other Names:
  • hycamptamine
  • Hycamtin
  • SKF S-104864-A
  • TOPO
Drug: vincristine sulfate
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Biological: filgrastim
Given SC
Other Names:
  • G-CSF
  • Neupogen
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm II (flexible filgrastim)
Patients receive filgrastim SC QD started on the first day after chemotherapy when ANC falls below 1,000/uL and stopped when ANC reaches at least 1,000/uL post nadir.
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: ifosfamide
Given IV
Other Names:
  • Cyfos
  • Holoxan
  • IFF
  • IFX
  • IPP
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Drug: topotecan hydrochloride
Given IV
Other Names:
  • hycamptamine
  • Hycamtin
  • SKF S-104864-A
  • TOPO
Drug: vincristine sulfate
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Biological: filgrastim
Given SC
Other Names:
  • G-CSF
  • Neupogen
Other: laboratory biomarker analysis
Correlative studies

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   1 Year to 25 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects must have or have had at initial diagnosis, histologic proof of their malignancy; additionally they must have radiographic, nuclear image, or biopsy proof that they have had a recurrence of their disease within four weeks prior to study entry; subjects must have failed or relapsed from standard first-line chemotherapy for their tumor; young children with primary embryonal brain tumor treated according to Head Start protocol are eligible as well; subjects with bone marrow involvement are NOT eligible for study
  • Patients will receive repeated cycles of identical chemotherapy that will likely result in grades III-IV hematological toxicity; patients will be treated outside of Children's Oncology Group (COG) protocols with specific requirements for schedule of G-CSF administration; the following categories of patients treated at Children's Hospital of Michigan are eligible for this study:

    • Patients with brain tumors treated according to modified Head Start II protocol with vincristine, etoposide, cyclophosphamide, and cisplatin (OPEC) chemotherapy;
    • Patients with recurrent Hodgkin lymphoma treated with ICE (ifosfamide, carboplatin, etoposide) chemotherapy;
    • Patients with recurrent solid tumors including sarcomas, Wilms' tumor, neuroblastomas, or brain tumors treated with high dose ICE or ICT (ifosfamide, carboplatin, topotecan) chemotherapy
  • Subjects must have fully recovered from the toxic effects of any prior therapy; at least 3 weeks should have elapsed since the last dose of chemotherapy (6 weeks in the case of nitrosourea containing therapy); subjects must have recovered from previous colony-stimulating factor therapy and have been off colony-stimulating factors (G-CSF, granulocyte macrophage colony-stimulating factor [GM-CSF], interleukin [IL]-11) for more than 10 days and off erythropoietin for 30 days
  • ANC > 1000/uL
  • Platelet count > 100,000/uL
  • Creatinine clearance or glomerular filtration rate (GFR) which is greater than or equal to 70 ml/min/1.73 m^2
  • Bilirubin less than 1.5 x normal limit (NL)
  • Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) less than 2.5 x NL for age
  • Subjects should have a normal ejection fraction (per institutional limits), no evidence of cardiac arrhythmias requiring therapy, and a fractional shortening of > 28%
  • All subjects must have a life expectancy of 12 weeks or more
  • Diagnostic categories

    • Sarcoma (soft tissue and bone)
    • Kidney tumors
    • Brain tumors
    • Other solid tumors (gonadal and germ cell tumors, retinoblastoma, neuroblastoma, and miscellaneous tumors)
    • Hodgkin lymphoma
  • Performance status must be > 60 from Lansky (age 1 to 16) or Karnofsky (age > 16)

Exclusion Criteria:

  • Subjects with any of the following will NOT be eligible for study:

    • Bone marrow involvement
    • Active myelogenous leukemia, or history of myelogenous leukemia
    • Pregnancy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01987596

Locations
United States, Michigan
Barbara Ann Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Maxim Y. Yankelevich    313-745-5515    myankele@med.wayne.edu   
Principal Investigator: Maxim Y. Yankelevich         
Sponsors and Collaborators
Barbara Ann Karmanos Cancer Institute
Children's Hospital of Michigan
Investigators
Principal Investigator: Maxim Yankelevich Barbara Ann Karmanos Cancer Institute
  More Information

No publications provided

Responsible Party: Maxim Yankelevich, Principal Investigator, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier: NCT01987596     History of Changes
Other Study ID Numbers: 2013-062, NCI-2013-02001, 2013-062, P30CA022453
Study First Received: November 12, 2013
Last Updated: June 21, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Glioblastoma
Hodgkin Disease
Glioma
Neuroblastoma
Neoplasms, Germ Cell and Embryonal
Astrocytoma
Sarcoma
Neoplasms
Ependymoma
Gliosarcoma
Osteosarcoma
Oligodendroglioma
Germinoma
Ovarian Neoplasms
Meningioma
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Medulloblastoma
Testicular Neoplasms
Teratoma
Wilms Tumor
Endodermal Sinus Tumor
Retinoblastoma
Choriocarcinoma
Craniopharyngioma
Adamantinoma
Kidney Neoplasms
Choroid Plexus Neoplasms
Optic Nerve Glioma
Neoplasms, Neuroepithelial

ClinicalTrials.gov processed this record on October 16, 2014