G-CSF and AMD3100 to Mobilize Stem Cells in Healthy Volunteers
Condition: Healthy
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): AMD 3100 (Mozobil plerixafor); Granulocyte colony-stimulating factor (G-CSF)
Intervention type(s): Drug; Drug
Intervention description(s): 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.; 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.
Other intervention name(s): AMD 3100; G-CSF
Intervention MeSH terms: Plerixafor; Lenograstim
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Hematopoietic Stem Cells; PBSC's; Mobilization; Alloreactivity; T Cell Polarization; Dendritic Cells; CXCR4; Plerixafor; Healthy Volunteer (HV)