Healthy Donor Study II - Comparing Plerixafor With G-CSF and Plerixafor

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.