Collection of Bone Marrow From Donors Treated With or Without Filgrastim

Phase 3

Completed

Conditions: No Evidence of Disease
Healthy Stem Cell Donor

Interventions: Procedure: Bone Marrow Donation
Biological: Filgrastim
Other: Laboratory Biomarker Analysis

Registration Number: NCT01149096

Lead Sponsor: Children's Oncology Group

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 13

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (conventional bone marrow harvest)	Bone Marrow Donation	Donors undergo conventional (i.e., unstimulated) bone marrow harvest on day 0.
Arm II (filgrastim, bone marrow harvest)	Laboratory Biomarker Analysis	Donors receive filgrastim subcutaneously on days -4 through 0. Donors then undergo bone marrow harvest on day 0.
Arm II (filgrastim, bone marrow harvest)	Filgrastim	Donors receive filgrastim subcutaneously on days -4 through 0. Donors then undergo bone marrow harvest on day 0.
Arm I (conventional bone marrow harvest)	Laboratory Biomarker Analysis	Donors undergo conventional (i.e., unstimulated) bone marrow harvest on day 0.
Arm II (filgrastim, bone marrow harvest)	Bone Marrow Donation	Donors receive filgrastim subcutaneously on days -4 through 0. Donors then undergo bone marrow harvest on day 0.

Primary Outcome Measures

Name	Time	Method
10-year Mortality Rate in Marrow Donors	Up to 10 years post bone marrow harvest	The Kaplan-Meier method will be used to estimate overall survival probabilities in standard BM and G-BM donors.
10-year Hematologic Cancer Rate	Up to 10 years post bone marrow harvest	The Kaplan-Meier method will be used to estimate hematologic cancer probabilities in standard BM and G-BM donors.
10-year Overall Cancer Incidence	Up to 10 years post bone marrow harvest	The Kaplan-Meier method will be used to estimate overall cancer free probabilities in standard BM and G-BM donors.
Percentage of Participants With Short-term Adverse Events in G-CSF (Filgrastim) Stimulated Bone Marrow (G-BM) Donors	Up to 1 year after donation	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.
Percentage of Participants Who Experienced Death in G-CSF Stimulated-bone Marrow (G-BM) Donors	Up to 1 year after donation	The Kaplan-Meier method will be used to estimate the cumulative incidence of death event in G-BM donors only.
Percentage of Participants With Grade 1 or 2 Toxicities	Up to 1 year after donation	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.
Percentage of Participants With Grade 3 or 4 Toxicities	Up to 1 year after donation	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.

Secondary Outcome Measures

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

Trial Locations

Locations (22): Lurie Children's Hospital-Chicago
🇺🇸
Chicago, Illinois, United States
Indiana University/Melvin and Bren Simon Cancer Center
🇺🇸
Indianapolis, Indiana, United States
Riley Hospital for Children
🇺🇸
Indianapolis, Indiana, United States
Johns Hopkins All Children's Hospital
🇺🇸
Saint Petersburg, Florida, United States
University of Mississippi Medical Center
🇺🇸
Jackson, Mississippi, United States
Norton Children's Hospital
🇺🇸
Louisville, Kentucky, United States
Children's Mercy Hospitals and Clinics
🇺🇸
Kansas City, Missouri, United States
Rainbow Babies and Childrens Hospital
🇺🇸
Cleveland, Ohio, United States
Nationwide Children's Hospital
🇺🇸
Columbus, Ohio, United States
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
UNC Lineberger Comprehensive Cancer Center
🇺🇸
Chapel Hill, North Carolina, United States
Children's Hospital of Philadelphia
🇺🇸
Philadelphia, Pennsylvania, United States
Childrens Oncology Group
🇺🇸
Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸
Pittsburgh, Pennsylvania, United States
Virginia Commonwealth University/Massey Cancer Center
🇺🇸
Richmond, Virginia, United States
UCSF Medical Center-Parnassus
🇺🇸
San Francisco, California, United States
Vanderbilt University/Ingram Cancer Center
🇺🇸
Nashville, Tennessee, United States
Primary Children's Hospital
🇺🇸
Salt Lake City, Utah, United States
Children's Hospital Colorado
🇺🇸
Aurora, Colorado, United States
New York Medical College
🇺🇸
Valhalla, New York, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
🇺🇸
Baltimore, Maryland, United States
C S Mott Children's Hospital
🇺🇸
Ann Arbor, Michigan, United States