AMD 3100 (Mozobil Plerixafor) to Mobilize Stem Cells for Donation
Condition: Healthy
Study type: Interventional
Phase: Phase 2

Summary: 
      Peripheral blood progenitor cells (PBPC) have become the preferred source of hematopoetic
      stem cells for allogeneic transplantation because of technical ease of collection and shorter
      time required for 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% will
      mobilize stem cells poorly and may require multiple large volume apheresis or bone marrow
      harvesting. Although G-CSF is generally well tolerated in healthy donors, it may be
      associated with bone pain, headache, myalgia and rarely life threatening side effects like
      stroke, myocardial infarction and splenic rupture.

      AMD3100, is a bicyclam compound that inhibits the binding of stromal cell derived factor-1
      (SDF-1) to its cognate receptor CXC- chemokine receptor 4 (CXCR4). CXCR4 is present on
      cluster of differentiation 34 (CD34)+ hematopoetic progenitor cells and its interaction with
      stromal cell derived factor 1 (SDF-1) plays a pivotal role in the homing of CD34+ cells in
      the bone marrow. Inhibition of the CXCR4-SDF1 axis by AMD3100 releases CD34+ cells into the
      circulation, which can then be collected easily by apheresis.

      Recently, a published report demonstrated that large numbers of CD34+ cells were rapidly
      mobilized in healthy volunteers following a single subcutaneous injection of AMD3100.
      Remarkably, the number of CD34+ cells collected by apheresis following a single injection of
      AMD3100 was comparable to the number of CD34+ cells collected from historical controls
      receiving 5 days of G-CSF prior to stem cell mobilization.

      In this study we will collect PBPCs following a single subcutaneous injection of AMD3100 from
      healthy donors who have previously had PBPC collected using standard G-CSF mobilization. The
      AMD3100 mobilized cells, G-CSF mobilized cells, and circulating cells prior to both AMD3100
      and G-CSF mobilization will be analyzed in terms of cellular content and function of
      lymphocytes, natural killer (NK) cells, and antigen presenting cells. AMD3100 mobilized PBPC
      will be collected for the purpose of research studies and will not be used for therapeutic
      purposes.
    

Detailed description: 
      Peripheral blood progenitor cells (PBPC) have become the preferred source of hematopoietic
      stem cells for allogeneic transplantation because of technical ease of collection and shorter
      time required for 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% will
      mobilize stem cells poorly and may require multiple large volume apheresis or bone marrow
      harvesting. Although G-CSF is generally well tolerated in healthy donors, it may be
      associated with bone pain, headache, myalgia and rarely life threatening side effects like
      stroke, myocardial infarction and splenic rupture.

      AMD3100 is a bicyclam compound that inhibits the binding of stromal cell derived factor-1
      (SDF-1) to its cognate receptor CXCR4. CXCR4 is present on CD34+ hematopoietic progenitor
      cells and its interaction with SDF-1 plays a pivotal role in the homing of CD34+ cells in the
      bone marrow. Inhibition of the CXCR4-SDF1 axis by AMD3100 releases CD34+ cells into the
      circulation, which can then be collected easily by apheresis. Recently, a published report
      demonstrated that large numbers of CD34+ cells were rapidly mobilized in healthy volunteers
      following a single subcutaneous injection of AMD3100. Remarkably, the number of CD34+ cells
      collected by apheresis following a single injection of AMD3100 was comparable to the number
      of CD34+ cells collected from historical controls receiving 5 days of G-CSF prior to stem
      cell mobilization. Although the study population is relatively small, side-effects to this
      agent have been mild and transient with no serious complications having been reported. The
      ability to collect a large quantity of PBPC with a single injection of this drug makes this
      an attractive agent for mobilizing donors of allogeneic PBPC. However, the immunologic
      profiles of AMD3100 mobilized cells, in terms of lymphocyte content (T cell, B cell, NK cell,
      immuno-regulatory T cell), T cell polarization status (TH1 versus TH2), status of antigen
      presenting cells (DC1 versus DC2), alloreactive potential, and preservation of reactivity to
      infectious agents [e.g. Epstein Barr Virus (EBV), Cytomegalovirus (CMV)] are unknown.
      Consequently, whether AMD3100 mobilized PBPC would be suitable for use as an allograft is
      uncertain. In this study we will collect PBPCs following a single subcutaneous injection of
      AMD3100 from healthy donors who have previously had PBPC collected using standard G-CSF
      mobilization. The AMD3100 mobilized cells, G-CSF mobilized cells, and circulating cells prior
      to both AMD3100 and G-CSF mobilization will be analyzed in terms of cellular content and
      function of lymphocytes, NK cells, and antigen presenting cells. AMD3100 mobilized PBPC will
      be collected for the purpose of research studies and will not be used for therapeutic
      purposes.

      The primary objective is to characterize the immunological properties of AMD3100 mobilized
      (cytokine gene expression profiles) T-cells compared to G-CSF mobilized T-cells.

      Secondary endpoints include the cellular content and other immune properties of AMD3100
      mobilized cells yields of hematopoietic progenitor cells, immune cells, and other cellular
      subsets collected by apheresis in subjects undergoing G-CSF and AMD3100 mobilization and the
      safety profile of AMD3100.
    

Intervention name(s): AMD3100 (Mozobil plerixafor)
Intervention type(s): Drug
Intervention description(s): AMD 3100 (Mozobil plerixafor)mobilized peripheral blood hematopoietic progenitor cells from healthy volunteers will be characterized by cellular content and immunological properties.
Other intervention name(s): Mozobil plerixafor
Intervention MeSH terms: Plerixafor
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Hematopoietic Stem Cells; Mobilization; Alloreactivity; T Cell Polarization; Dendritic Cells; Plerixafor; Mozobil; Healthy Volunteer (HV)