Healthy Stem Cell Donor, No Evidence of Disease
Conditions
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.
Interventions
PROCEDUREBone Marrow Donation
Undergo bone marrow harvest
BIOLOGICALFilgrastim
Given subcutaneously
OTHERLaboratory Biomarker Analysis
Optional correlative studies
Sponsors
National Cancer Institute (NCI)
Children's Oncology Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm I (Conventional Bone Marrow Harvest) Donors undergo conventional (i.e., unstimulated) bone marrow harvest on day 0.
Bone Marrow Donation: Undergo bone marrow harvest
Laboratory Biomarker Analysis: Optional correlative studies | 6 |
| Arm II (Filgrastim, Bone Marrow Harvest) Donors receive filgrastim subcutaneously on days -4 through 0. Donors then undergo bone marrow harvest on day 0.
Bone Marrow Donation: Undergo bone marrow harvest
Filgrastim: Given subcutaneously
Laboratory Biomarker Analysis: Optional correlative studies | 7 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | Arm I (Conventional Bone Marrow Harvest) | Arm II (Filgrastim, Bone Marrow Harvest) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 6 Participants | 5 Participants | 11 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 2 Participants | 2 Participants |
| Age, Continuous | 6.5 years STANDARD_DEVIATION 5.2 | 14.4 years STANDARD_DEVIATION 5.9 | 10.8 years STANDARD_DEVIATION 6.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 6 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 7 Participants | 13 Participants |
| Region of Enrollment United States | 6 participants | 7 participants | 13 participants |
| Sex: Female, Male Female | 2 Participants | 5 Participants | 7 Participants |
| Sex: Female, Male Male | 4 Participants | 2 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 7 |
| other Total, other adverse events | 4 / 6 | 6 / 7 |
| serious Total, serious adverse events | 0 / 6 | 0 / 7 |
Outcome results
Primary
10-year Hematologic Cancer Rate
The Kaplan-Meier method will be used to estimate hematologic cancer probabilities in standard BM and G-BM donors.
Time frame: Up to 10 years post bone marrow harvest
Population: Data were not collected as no patients were followed to 10 years.
Primary
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.
Time frame: Up to 10 years post bone marrow harvest
Population: Data were not collected as no patients were followed to 10 years.
Primary
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.
Time frame: Up to 10 years post bone marrow harvest
Population: Data were not collected as no patients were followed to 10 years.
Primary
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.
Time frame: Up to 1 year after donation
Population: Analysis conducted for stimulated-bone marrow (G-BM) donors only, therefore, no report on the control arm (Conventional bone marrow transplant).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm II (Filgrastim, Bone Marrow Harvest) | Percentage of Participants Who Experienced Death in G-CSF Stimulated-bone Marrow (G-BM) Donors | 0 Percentage of patients |
Primary
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.
Time frame: Up to 1 year after donation
Population: Modified Toxicity Criteria and Pain Assessment was used with higher grades corresponding to more severe AEs.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm II (Filgrastim, Bone Marrow Harvest) | Percentage of Participants With Grade 1 or 2 Toxicities | 67 percentage of patients |
| Arm II (Filgrastim, Bone Marrow Harvest) | Percentage of Participants With Grade 1 or 2 Toxicities | 86 percentage of patients |
Primary
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.
Time frame: Up to 1 year after donation
Population: All patients included in analysis. No incidence of grades 3 or 4 toxicities.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm II (Filgrastim, Bone Marrow Harvest) | Percentage of Participants With Grade 3 or 4 Toxicities | 0 percentage of patients |
| Arm II (Filgrastim, Bone Marrow Harvest) | Percentage of Participants With Grade 3 or 4 Toxicities | 0 percentage of patients |
Primary
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.
Time frame: Up to 1 year after donation
Population: Analysis conducted within G-BM donors only, therefore, no report for the control arm (Conventional bone marrow transplant).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm II (Filgrastim, Bone Marrow Harvest) | Percentage of Participants With Short-term Adverse Events in G-CSF (Filgrastim) Stimulated Bone Marrow (G-BM) Donors | 0 Percentage of patients |
Secondary
Absolute T Cell Numbers
Median and interquartile range of the outcome measure in standard BM and G-BM donors.
Time frame: Up to 1 year after donation
Population: Data were not collected for this study.
Secondary
Dendritic Cell (DC) Populations
Median and interquartile range of the outcome measure in standard BM and G-BM donors.
Time frame: Up to 1 year after donation
Population: Data were not collected for this study.
Secondary
Th1 vs. Th2 Profile of T Cells
Proportion of donors with Th1-T cell profile in standard BM and G-BM donors.
Time frame: Up to 1 year after donation
Population: Data were not collected for this study.
Secondary
T Regulatory Cell Content
Median and interquartile range of the outcome measure in standard BM and G-BM donors.
Time frame: Up to 1 year after donation
Population: Data were not collected for this study.