Clinical trial NCT00082329
Conditions: Healthy
Keywords: Hematopoietic Stem Cells PBSC's Mobilization Alloreactivity T Cell Polarization Dendritic Cells CXCR4 Plerixafor Healthy Volunteer (HV)
Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
Start date: 2004-06-18; Completion date: 2012-10-25
Enrollment: 9 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This 12-day study will test whether the combination of G-CSF (granulocyte-colony stimulating factor) and AMD3100 (Mozobil) is more efficient in mobilizing stem cells for collection than the use of G-CSF alone. Traditionally, the growth factor G-CSF has been given to stem cell donors to mobilize, or push, stem cells out of the bone marrow and into the blood circulation for collection for transplantation. Although a sufficient quantity of cells usually can be collected with G-CSF treatment, some donors do not respond well and may require multiple apheresis procedures (see below) to collect enough cells. Studies indicate that G-CSF used together with a drug called AMD3100 may be more effective in mobilizing stem cells for collection than G-CSF alone. The Food and Drug Administration has approved G-CSF for stem cell mobilization. AMD3100 is a new drug that also mobilizes stem cells in large numbers within a few hours.

Normal healthy volunteers between 18 and 60 years of age may be eligible for this study.

Detailed description:
Peripheral blood progenitor cells (PBPC) are the most popular source of hematopoetic stem cells for allogeneic transplantation because of technical ease of collection and faster engraftment. Traditionally, granulocyte-colony stimulating factor (G-CSF) has been used to procure the peripheral blood stem cell graft. Although regimens using G-CSF usually succeed in collecting adequate numbers of PBPC from healthy donors, 5%-10% of the donors will mobilize stem cells poorly and may require multiple large volume apheresis or bone marrow harvesting. AMD3100 reversibly inhibits CXC- chemokine receptor 4 (CXCR4) binding to stromal cell derived factor (SDF) - 1 and was recently discovered to be an effective agent to mobilize cluster of differentiation 34 (CD34)+ cells into the peripheral blood. In normal volunteers, administering AMD3100 after 4-5 days of G-CSF resulted in a 3-3.5 fold increase in circulating CD34 cells compared to G-CSF alone. Recent data has suggested that the combination of G-CSF and AMD3100 is superior to G-CSF alone for mobilizing hematopoietic progenitor cells in heavily pretreated patients with multiple myeloma or non-Hodgkin's lymphoma undergoing autologous hematopoietic transplantation. Combining AMD3100 with G-CSF could be an effective strategy to improve the yield of PBPC collected from allogeneic donors who mobilize poorly with G-CSF alone. However, the biological impact of AMD3100 in this context on T cells and other cellular populations contained within the allograft that mediate graft versus host disease (GVHD) and graft-versus-leukemia (GVL) effects are unknown.

We propose to collect peripheral progenitor cell (PBPC) from healthy volunteers following 5 days of G-CSF (10 mcg/kg/day) and a single dose of AMD3100 (240 mcg/kg subcutaneous given 12 hours before starting apheresis) to study the impact of combining these two mobilizing agents on the immunological properties of the mobilized cells. A single 15 liter apheresis will be conducted on day 5 following the 5th dose of G-CSF. The immunological studies conducted on these mobilized cells will be the same as our parallel study which is investigating the immune properties of PBPCs mobilized with G-CSF or AMD3100 alone. If combining AMD3100 with G-CSF has no negative impact on the immune populations involved in GVHD and graft-vs-leukemia effects, this regimen could be used for allogeneic donors who fail to mobilize sufficient peripheral blood stem cell (PBSC) using G-CSF alone.

Primary objective: To determine the cytokine polarization status of cluster of differentiation 4 (CD4+) T-cells collected by apheresis following combination of AMD3100 and G-CSF compared to G-CSF mobilization.

Primary endpoint: the ratio of Th1 \[intracellular interferon (IFN-g) +\] versus Th2 \[intracellular interleukin (IL-4+)\] T-cells in the apheresis products collected from individual donors undergoing mobilization with combination of G-CSF and AMD3100 to the ratio in apheresis product collected with G-CSF alone (ratio published in literature).

Secondary endpoints: To examine 1) the cellular content and other immune properties of mobilized cells; 2) yields of hematopoietic progenitor cells, immune cells, and other cellular subsets collected by apheresis; and the 3) safety profile of AMD3100.

Arms: arm 1: Participants received subcutaneous injection of G-CSF (10 mcg/kg/day) for 5 days followed by a single subcutaneous injection of AMD3100 (240 mcg/kg) given 12 hours prior to apheresis peripheral blood stem cell collection. Peripheral blood stem cell collection performed on the fifth day of G-CSF administration.
Interventions: intervention 1: AMD 3100 (Mozobil plerixafor) intervention 2: Granulocyte colony-stimulating factor (G-CSF)
Intervention descriptions: intervention 1: Participants received subcutaneous injection of granulocyte colony-stimulating factor (G-CSF) at 10 mcg/kg/day for 5 days followed by a single subcutaneous injection of AMD3100 (240 mcg/kg) given 12 hours prior to apheresis peripheral blood stem cell collection. Peripheral blood stem cell collection performed on the fifth day of G-CSF administration. intervention 2: Participants received subcutaneous injection of granulocyte colony-stimulating factor (G-CSF) at 10 mcg/kg/day for 5 days followed by a single subcutaneous injection of AMD3100 (240 mcg/kg) given 12 hours prior to apheresis peripheral blood stem cell collection. Peripheral blood stem cell collection performed on the fifth day of G-CSF administration.

Protocol documents: