Collection of Bone Marrow From Donors Treated With or Without Filgrastim

A Comparison of Acute and Long-term Toxicities in Bone Marrow Donors With and Without G-CSF Treatment Prior to Harvest: A Companion Study to ASCT0631

This randomized clinical trial is studying the side effects of collection of bone marrow from donors treated with or without filgrastim. Giving colony-stimulating factors, such as filgrastim (G-CSF), to donors helps the stem cells move from the bone marrow to the blood so they can be collected and stored.

Study Overview

• Status: Completed
• Conditions: No Evidence of Disease; Healthy Stem Cell Donor
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Procedure: Bone Marrow Donation; Biological: Filgrastim

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate short- and long-term toxicities in bone marrow donors treated with vs without filgrastim before harvest.

II. To compare 10-year mortality and cancer in donors treated with vs without filgrastim.

SECONDARY OBJECTIVES:

I. To correlate the incidence of acute and chronic graft-vs-host disease in the marrow recipients enrolled on COG-ASCT0631 with four parameters assessed in the bone marrow harvests: absolute T-cell numbers, Th1 vs Th2 profile of T-cells, dendritic cell populations, and T-regulatory cell content.

OUTLINE: Donors are randomized to 1 of 2 treatment arms.

ARM I (unstimulated harvest): Donors undergo conventional (i.e., unstimulated) bone marrow harvest on day 0.

ARM II (stimulated harvest): Donors receive filgrastim subcutaneously on days -4 through 0. Donors then undergo bone marrow harvest on day 0.

After completion of study treatment, donors are followed up at 1, 6, and 12 months and then annually for up to 10 years.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • UCSF Medical Center-Parnassus
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Florida
    • Saint Petersburg, Florida, United States, 33701
      • Johns Hopkins All Children's Hospital
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Lurie Children's Hospital-Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University/Melvin and Bren Simon Cancer Center
    • Indianapolis, Indiana, United States, 46202
      • Riley Hospital for Children
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Children's Hospital
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University/Sidney Kimmel Cancer Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • C S Mott Children's Hospital
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospitals and Clinics
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • Valhalla, New York, United States, 10595
      • New York Medical College
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • UNC Lineberger Comprehensive Cancer Center
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Rainbow Babies and Childrens Hospital
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Philadelphia, Pennsylvania, United States, 19104
      • Childrens Oncology Group
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh of UPMC
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University/Ingram Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • Primary Children's Hospital
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University/Massey Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Appropriately human leukocyte antigen (HLA)-matched (HLA, A, B, DRB1 identical or antigen mismatched [i.e., 5/6 or 6/6 antigens matched]) sibling of the bone marrow recipient enrolled on COG-ASCT0631
• Adequate size relative to the recipient (i.e., harvesting the maximum of 20 cc/kg from the donor would result in a bone marrow graft that will provide an adequate cell and volume dose to the recipient, in the opinion of the treating physician)
• Enrolled on the COG Umbrella Long-Term Follow-Up Study COG-ALTE05N1
• Not pregnant or nursing
• No human immunodeficiency virus (HIV) positivity
• No sickle cell trait or sickle cell anemia/disease
• Not at an increased risk from bone marrow donation after filgrastim administration due to a pre-existing medical condition, as determined by an independent physician separate from the research team

• None of the following:

  • Active infection, especially pulmonary
  • Splenomegaly or a history of splenic injury
  • Active or recent pulmonary disease (i.e., pneumonia within the past 4 weeks)
  • A condition that would make the donor unsuitable to donate, as determined by an independent physician separate from the research team
• No autoimmune disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm I (conventional bone marrow harvest); Donors undergo conventional (i.e., unstimulated) bone marrow harvest on day 0.	Other: Laboratory Biomarker Analysis; Optional correlative studies; Procedure: Bone Marrow Donation; Undergo bone marrow harvest
Experimental: Arm II (filgrastim, bone marrow harvest); Donors receive filgrastim subcutaneously on days -4 through 0. Donors then undergo bone marrow harvest on day 0.	Other: Laboratory Biomarker Analysis; Optional correlative studies; Procedure: Bone Marrow Donation; Undergo bone marrow harvest; Biological: Filgrastim; Given subcutaneously; Other Names: G-CSF; r-metHuG-CSF; Neupogen; Recombinant Methionyl Human Granulocyte Colony Stimulating Factor; rG-CSF; Tevagrastim

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Short-term Adverse Events in G-CSF (Filgrastim) Stimulated Bone Marrow (G-BM) Donors	The Kaplan-Meier method will be used to estimate the cumulative incidence of short term adverse events defined by having any of the following events: 1) death due to a cause that is unknown or possibly related to G-CSF, 2) development of a malignancy, 3) development of a splenic rupture, or 4) development of a severe acute lung injury possibly related to GCSF therapy.	Up to 1 year after donation
Percentage of Participants Who Experienced Death in G-CSF Stimulated-bone Marrow (G-BM) Donors	The Kaplan-Meier method will be used to estimate the cumulative incidence of death event in G-BM donors only.	Up to 1 year after donation
Percentage of Participants With Grade 1 or 2 Toxicities	Estimate the percentage of patients having non-fatal complications of CTCAE Grades 1 or 2 in standard BM and G-CSF stimulated-bone marrow (G-BM) donors.	Up to 1 year after donation
Percentage of Participants With Grade 3 or 4 Toxicities	Estimate the percentage of patients having non-fatal complications of Grade 3 other than pain (consider Grade 4 for pain only), or any of Grade 4 in standard BM and G-CSF stimulated-bone marrow (G-BM) donors. Modified Toxicity Criteria and Pain Assessment was used with higher grades corresponding to more severe AEs.	Up to 1 year after donation
10-year Mortality Rate in Marrow Donors	The Kaplan-Meier method will be used to estimate overall survival probabilities in standard BM and G-BM donors.	Up to 10 years post bone marrow harvest
10-year Overall Cancer Incidence	The Kaplan-Meier method will be used to estimate overall cancer free probabilities in standard BM and G-BM donors.	Up to 10 years post bone marrow harvest
10-year Hematologic Cancer Rate	The Kaplan-Meier method will be used to estimate hematologic cancer probabilities in standard BM and G-BM donors.	Up to 10 years post bone marrow harvest

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute T Cell Numbers	Median and interquartile range of the outcome measure in standard BM and G-BM donors.	Up to 1 year after donation
Th1 vs. Th2 Profile of T Cells	Proportion of donors with Th1-T cell profile in standard BM and G-BM donors.	Up to 1 year after donation
Dendritic Cell (DC) Populations	Median and interquartile range of the outcome measure in standard BM and G-BM donors.	Up to 1 year after donation
T Regulatory Cell Content	Median and interquartile range of the outcome measure in standard BM and G-BM donors.	Up to 1 year after donation

Collaborators and Investigators

• Sponsor: Children's Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Stephan A Grupp, Children's Oncology Group

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2010
• Primary Completion (Actual): December 14, 2011
• Study Completion (Actual): September 30, 2016

Study Registration Dates

• First Submitted: June 22, 2010
• First Submitted That Met QC Criteria: June 22, 2010
• First Posted (Estimate): June 23, 2010

Study Record Updates

• Last Update Posted (Actual): February 26, 2020
• Last Update Submitted That Met QC Criteria: February 13, 2020
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Adjuvants, Immunologic; Lenograstim
• Other Study ID Numbers: ASCT0631D (Other Identifier: CTEP); U10CA098543 (U.S. NIH Grant/Contract); NCI-2011-02237 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); CDR0000675536; COG-ASCT0631D

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No