Collection of Bone Marrow From Donors Treated With or Without Filgrastim

Study Overview
=================
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.

Official Title
-----------------
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

Conditions
-----------------
Healthy Stem Cell Donor, No Evidence of Disease

Intervention / Treatment
-----------------
* Procedure: Bone Marrow Donation
* Biological: Filgrastim
* Other: Laboratory Biomarker Analysis


Participation Criteria
=================
Eligibility Criteria
-----------------
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
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm I (conventional bone marrow harvest)<br>Donors undergo conventional (i.e., unstimulated) bone marrow harvest on day 0. | Procedure: Bone Marrow Donation<br>* Undergo bone marrow harvest<br>Other: Laboratory Biomarker Analysis<br>* Optional correlative studies<br>|
| Experimental: Arm II (filgrastim, bone marrow harvest)<br>Donors receive filgrastim subcutaneously on days -4 through 0. Donors then undergo bone marrow harvest on day 0. | Procedure: Bone Marrow Donation<br>* Undergo bone marrow harvest<br>Biological: Filgrastim<br>* Given subcutaneously<br>* Other names: Tevagrastim;Other: Laboratory Biomarker Analysis<br>* Optional correlative studies<br>|

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 |