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

Primary Purpose

Childhood Choroid Plexus Tumor, Childhood Medulloblastoma, Childhood Pineoblastoma

Status
Terminated
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
filgrastim
Sponsored by
Barbara Ann Karmanos Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Childhood Choroid Plexus Tumor

Eligibility Criteria

1 Year - 25 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Subjects must have or have had at initial diagnosis, histologic proof of their malignancy; young children with primary embryonal brain tumor treated according to Head Start protocol are eligible; 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 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
    • Patients with UH Wilms' tumor treated with CE (cyclophosphamide, etoposide); patients with neuroblastoma treated with CE (carboplatin, etoposide);
    • Patients with soft tissue sarcomas treated with IA (ifosfamide, doxorubicin);
    • Patients with osteosarcoma treated with high dose ifosfamide
  • 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

Sites / Locations

  • Barbara Ann Karmanos Cancer Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm I (fixed filgrastim)

Arm II (flexible filgrastim)

Arm Description

Patients receive filgrastim SC QD started at 24 hours after completion of chemotherapy and stopped when ANC reaches at least 1,000/uL post nadir.

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.

Outcomes

Primary Outcome Measures

Days to ANC Greater Than or Equal to 1,000/uL From the Start of Chemotherapy
Time in days until absolute neutrophil count (ANC) recovery to greater than or equal to 1,000/uL from the start of chemotherapy

Secondary Outcome Measures

Incidence of Febrile Neutropenia
occurrence of febrile neutropenia
Cumulative GCSF Dose
Cumulative GCSF dose - number of GCSF injections until ANC recovery greater than or equal to 1,000/uL from the start of chemotherapy
Days to First G-CSF Dose
Time (in days) to first G-CSF dose

Full Information

First Posted
November 12, 2013
Last Updated
October 2, 2020
Sponsor
Barbara Ann Karmanos Cancer Institute
Collaborators
National Cancer Institute (NCI), Children's Hospital of Michigan
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1. Study Identification

Unique Protocol Identification Number
NCT01987596
Brief Title
Study of Fixed vs. Flexible Filgrastim to Accelerate Bone Marrow Recovery After Chemotherapy in Children With Cancer
Official Title
Prospective and Randomized Study of Fixed Versus Flexible Prophylactic Administration of Granulocyte Colony-Stimulating Factor (G-CSF) in Children With Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
October 2020
Overall Recruitment Status
Terminated
Study Start Date
August 2013 (undefined)
Primary Completion Date
June 2018 (Actual)
Study Completion Date
June 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Barbara Ann Karmanos Cancer Institute
Collaborators
National Cancer Institute (NCI), Children's Hospital of Michigan

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
Detailed Description
PRIMARY OBJECTIVES: I. To compare the effect of flexible vs. fixed administration of G-CSF (filgrastim) on the parameters of hematological recovery including duration of absolute neutrophil count (ANC) < 500/uL; time to ANC recovery >= 1,000/uL and time to platelet recovery >= 75,000/uL in children receiving myelotoxic chemotherapy. SECONDARY OBJECTIVES: I. To compare the effect of flexible vs. fixed administration of G-CSF on the incidence of febrile neutropenia and number of hospital days on antibiotics following myelotoxic chemotherapy. II. To evaluate the number of days of platelet transfusion events after chemotherapy cycles with flexible vs. fixed administration of G-CSF. III. To evaluate on the incidence and duration of G-CSF-related side effects including extremities/back pain and headaches after chemotherapy courses followed by flexible vs. fixed administration of G-CSF. IV. To evaluate the peripheral blood progenitor responses and subsets of progenitor cells (cluster of differentiation [CD]34/41/61/117/10/19/11b/33) to chemotherapy followed by flexible vs. fixed administration of G-CSF. OUTLINE: CHEMOTHERAPY: Depending on their diagnosis patients are assigned to 1 of 3 chemotherapy regimens. ICE: Patients receive etoposide intravenously (IV) over 1 hour on days 1-3, ifosfamide IV over 3 hours on days 1-3, and carboplatin IV over 1 hour on day 4. Patients with recurrent Hodgkin lymphoma receive etoposide and ifosfamide on days 1-3 and carboplatin on day 3. ICT: Patients receive topotecan hydrochloride IV over 30 minutes on days 1-3, and ifosfamide and carboplatin as in ICE. OPEC: Patients receive vincristine sulfate on days 1, 8, and 15; etoposide IV over 1 hour on days 1-3; cyclophosphamide IV over 1 hour on days 1-2; and cisplatin IV over 6 hours on day 4. For all chemotherapy regimens, treatment repeats every 21 days for 2 courses. Patients are then randomized to 1 of 2 treatment arms. ARM I (fixed filgrastim): Patients receive filgrastim subcutaneously (SC) once daily (QD) started at 24 hours after completion of chemotherapy and stopped when ANC reaches at least 1,000/uL post nadir. 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. After completion of the first filgrastim treatment, patients cross-over to the other filgrastim arm and repeat the same course of chemotherapy as before. After completion of the second filgrastim treatment, chemotherapy treatment may continue for up to 5 (OPEC) or 6 (ICE, ICT) courses in the absence of disease progression or unacceptable toxicity.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Childhood Choroid Plexus Tumor, Childhood Medulloblastoma, Childhood Pineoblastoma, Childhood Soft Tissue Sarcoma, Childhood Supratentorial Primitive Neuroectodermal Tumor, Neuroblastoma, Osteosarcoma, Retinoblastoma, Wilms Tumor and Other Childhood Kidney Tumors, Recurrent/Refractory Childhood Hodgkin Lymphoma, Unspecified Childhood Solid Tumor, Protocol Specific

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
23 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I (fixed filgrastim)
Arm Type
Experimental
Arm Description
Patients receive filgrastim SC QD started at 24 hours after completion of chemotherapy and stopped when ANC reaches at least 1,000/uL post nadir.
Arm Title
Arm II (flexible filgrastim)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
filgrastim
Other Intervention Name(s)
G-CSF, Neupogen
Intervention Description
Given SC once daily starting on day 1 after chemotherapy in Arm I (fixed) and on any day when ANC drops below 1000/mcl in Arm II (flexible)
Primary Outcome Measure Information:
Title
Days to ANC Greater Than or Equal to 1,000/uL From the Start of Chemotherapy
Description
Time in days until absolute neutrophil count (ANC) recovery to 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
Secondary Outcome Measure Information:
Title
Incidence of Febrile Neutropenia
Description
occurrence of febrile neutropenia
Time Frame
Up to 1 year
Title
Cumulative GCSF Dose
Description
Cumulative GCSF dose - number of GCSF injections until ANC recovery greater than or equal to 1,000/uL from the start of chemotherapy
Time Frame
up until engraftment
Title
Days to First G-CSF Dose
Description
Time (in days) to first G-CSF dose
Time Frame
time to ANC 1000

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
25 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects must have or have had at initial diagnosis, histologic proof of their malignancy; young children with primary embryonal brain tumor treated according to Head Start protocol are eligible; 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 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 Patients with UH Wilms' tumor treated with CE (cyclophosphamide, etoposide); patients with neuroblastoma treated with CE (carboplatin, etoposide); Patients with soft tissue sarcomas treated with IA (ifosfamide, doxorubicin); Patients with osteosarcoma treated with high dose ifosfamide 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Maxim Yankelevich
Organizational Affiliation
Barbara Ann Karmanos Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Barbara Ann Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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