Trial Information

A Pilot Study To Design a Clinical Trial That Will Compare the Ability of Plerixafor Alone Versus Plerixafor Plus G-CSF To Generate a Bone Marrow Versus Blood Transplant Product In Normal Healthy Adults

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.