Healthy Donor Study II - Comparing Plerixafor With G-CSF and Plerixafor
Condition: Malignant Lymphoma, Stem Cell Type
MeSH terms: Lymphoma
Study type: Interventional
Phase: Phase 2

Summary: 
      Stem cells can be transplanted from a healthy donor to a patient to combat blood cancers and
      other disorders. This process is called stem cell transplantation. Stem cells normally live
      in the bone marrow. A bone marrow transplantation (BMT) is when the bone marrow is directly
      transplanted into a patient. However, stem cells can also be stimulated to move from the bone
      marrow to the blood where they can be collected, a process is called mobilization. When these
      stem cells are transplanted it is called peripheral blood stem cell transplantation (PBSCT).
      Both stem cell sources are used for different reasons, but PBSCT is much more common.

      There is considerable debate as to which stem cell source, BMT or PBSCT, is optimal. There
      are differences between the two sources in important transplant outcomes. The stem cell
      product that is transplanted, also called the stem cell graft, contains more than just stem
      cells. Results from studies suggest that the variation in the cells with grafts may account
      for the variation in outcomes. Preliminary data from a recent study conducted by the Canadian
      Blood and Bone Marrow Transplant Group has associated relative frequencies of particular cell
      populations with leukemic relapse and another important outcome called graft versus host
      disease (GVHD). While the later essentially equates to a failed transplant, the former is the
      most common and devastating complication of stem cell transplantation.

      The only drug used to mobilize stem cells into the blood of health donors for collection is
      G-CSF. However there is a new mobilization drug recently approved called plerixafor. This
      drug is able to mobilize stem cells when G-CSF has failed and pre-clinical studies suggest
      that it may produce a superior stem cell graft to G-CSF alone. There is little information
      available, besides safety and efficacy data, about the effects that plerixafor has on the
      stem cell graft of normal healthy donors.

      This study will compare the stem cell graft in normal healthy donors following plerixafor
      mobilization versus plerixafor and G-CSF mobilization. Specifically, they will look at the
      cell populations that have been previously correlated with important transplantation outcomes
      like relapse and GVHD. The investigators suspect that the stem cell graft mobilized by
      plerixafor and G-CSF will provide a superior graft to that mobilized by plerixafor alone.
    

Detailed description: 
      Background:

      Stem cell transplantation (SCT) involves transfusing stem cells collected from 3 potential
      sources: bone marrow, peripheral blood, or umbilical cord. There are 2 major types of
      transplantation. Autologous SCT involves transplanting the patients own stem cells, while
      allogeneic transplantation involves transplanting stem cells from someone else. Whatever the
      source, the transplanted stem cell product is called the graft. Currently, the most common
      source is peripheral blood, However, there is considerably debate as to the optimal stem cell
      source because different sources have been associated with different transplant outcomes. One
      key outcome is graft versus host disease (GVHD). This is the most common complication of SCT
      and contributes significantly to transplant morbidity and mortality, as well as relapse.

      Stem cells normally populate the bone marrow. Drugs are used to encourage stem cells to go
      into the peripheral blood, a process call mobilization. In the peripheral blood stem cells
      can be collected and subsequently transplanted. In Canada, the only drug used to mobilize
      stem cells from donors is filgrastim, a form of granulocyte colony stimulating factor
      (G-CSF). Although well tolerated, there are some shortcomings to this agent and there is
      clearly room to improve in terms of the donor experience and providing the optimal stem cell
      graft.

      A soon to be completed study conducted by the Canadian Blood and Bone Marrow Transplant Group
      (CBMTG), called CBMTG 0601, is evaluating the best stem cell source. The study is aimed to
      compare the outcomes between allogeneic transplant patients who receive either G-CSF
      stimulated bone marrow or peripheral blood. This will be a seminal study that should provide
      valuable information as to the optimal stem cell source in allogeneic SCT. Early results
      suggest that the investigators may be able to predict important SCT outcomes, such as
      transplant related mortality, relapse or graft versus host disease, by looking at cell
      populations in the graft.

      Plerixafor is a new mobilization agent that is approved for use in combination with neupogen
      in myeloma and relapsed lymphoma who are undergoing an autologous SCT. Following numerous
      publications on the safety and dosing of plerixafor, there were 2 pivotal high quality
      studies performed in this patient population. The results of this study lead to FDA approval,
      and Health Canada approval is close. Plerixafor may be a clinically superior mobilizing agent
      to Neupogen. More importantly though, it has a formidable safety profile and arguably
      superior in this respect. There has also been a case report and a trial demonstrating both
      the safety and efficacy of plerixafor in healthy donors as well. Finally, preclinical work
      suggests that plerixafor mobilization may yield a superior graft. Taken together, this work
      supports the notion that plerixafor may be a superior mobilization agent over neupogen.

      Rationale:

      Considering the shortcomings of neupogen and the demonstrated potential of plerixafor in
      trials with autologous SCT patients, it would be logical to further investigate the efficacy
      of plerixafor in normal healthy donors for allogeneic SCT. The investigators can confidently
      state that plerixafor is safe. Furthermore, plerixafor can mobilize myeloma and lymphoma
      patients who have failed neupogen mobilization. However, although suggested in preclinical
      data, there is no firm evidence to suggest that plerixafor mobilization provides a superior
      stem cell graft. The investigators will administer either plerixafor or plerixafor and
      neupogen then compare the cell populations in both peripheral blood and bone marrow..

      Importance:

      The use of SCT has steadily increased in the last 20 years. This has especially increased
      since using neupogen to mobilize stem cells thereby making transplants easier. Now that there
      is a new agent available that is likely safer and perhaps more efficacious, its use may
      improve both donor experience and patient outcomes. If plerixafor grafts consist of cell
      populations that are associated with superior transplant outcomes as determined in CBMTG
      0601, then it will likely be used in an upcoming larger clinical trial comparing neupogen and
      plerixafor in normal healthy donors.

      Objectives:

      Our primary objective is to determine the best timing for harvesting stem cells from normal
      donors given plerixafor with or without neupogen. A secondary objective is to evaluate and
      compare the change over time after plerixafor with or without neupogen administration on the
      population of cells in the graft predicted to give superior transplant outcomes. The other
      secondary objective is to evaluate and compare the change over time after plerixafor with or
      without neupogen administration on the concentration of cells in the PB and BM of normal
      donors predicted to give GVHD or relapse. The investigators hypothesise that plerixafor with
      neupogen will provide a graft with increased cell populations associated with superior SCT
      outcomes.
    

Intervention name(s): Plerixafor (Mozobil); Plerixafor + G-CSF
Intervention type(s): Drug; Drug
Intervention description(s): They will receive Plerixafor (240 µg/kg/day subcutaneously for 1 dose) on Day 0 at 8 am; They will receive G-CSF (5 µg/kg/day) for 4 days (Days -4,-3,-2,-1 at 8 am) followed by Plerixafor (240 µg/kg/day subcutaneously for 1 dose) on Day 0 at 8 am
Other intervention name(s): Mozobil; AMD 3100; Mozobil; AMD 3100; Neupogen
Intervention MeSH terms: Plerixafor
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Hematopoietic Stem Cell Transplantation; Plerixafor; Healthy Donors; Stem Cell Graft