PAV-trial: Plerixafor and Chemotherapy With Vinorelbine for Stem Cell Mobilization in Patients With Myeloma. A Pilot Phase II Study.
High-dose chemotherapy with autologous stem cell support is the current standard procedure
in the first-line treatment in younger patients with myeloma fit for intensive treatment.
Current practice in Switzerland for stem cell mobilization is the combination of
chemotherapy and G-CSF stimulation in myeloma patients fit for high-dose chemotherapy with
melphalan and autologous stem cell transplant. For mobilization chemotherapy, a single dose
of vinorelbine is commonly used, producing mild myelosuppression. G-CSF is started at day 4
on a daily basis, allowing stem cell apheresis usually at day 8. In a subsequent study, we
evaluated the use of pegylated G-CSF given as a single injection at day 4 together with
vinorelbine. We found this regimen equally feasible, reliable and allowing collection of
stem cells in an equally high percentage. In the current proposal, we suggest to continue
this line of research investigating the mobilization using chemotherapy with vinorelbine. We
propose to study the feasibility of this mobilization chemotherapy in the absence of growth
factors, thus without G-CSF, in combination with Plerixafor.
Primary objective: To assess the feasibility of collection of > 6 million CD34+ peripheral
blood stem cells/kg body weight in 2 days.
Secondary objectives: Assessment of safety of plerixafor during mobilization and collection
of peripheral blood stem cells; feasibility of intravenous plerixafor application and stem
cell apheresis in a one-day procedure on an ambulatory basis; evaluation of engraftment of
peripheral blood stem cells mobilized by vinorelbine and plerixafor; evaluation of the costs
for mobilization with plerixafor.
Chemotherapy with vinorelbine is given at a standard dose at day 1, on an ambulatory basis.
In part A (10 patients), G-CSF is given s.c., divided in two daily doses starting at day 4
until collection of stem cells. Plerixafor is given as an i.v. application on day 8 in the
dose of 240 microg/kg b.w. Stem cell collection is initiated 4 hours later at day 8, if at
least 20 x 103 of CD34+ cells / ml peripheral blood are detected. In case of insufficient
collection, the procedure is repeated at day 9, including repetition of plerixafor
Part B (30 patients): If the combination of plerixafor and vinorelbine is found feasible and
in the absence of unexpected toxicity, additional 30 patients will be studied in part B of
this study. No G-CSF will be administered in part B, otherwise the treatment plan is as it
is in part A.
High dose Melphalan will be used as conditioning regimen. After transplantation, G-CSF will
be given to subjects starting at day +5 after PBPC reinfusion.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Number of CD34+ peripheral blood stem cells/kg
day 8 (and 9, if necessary)
Thomas Pabst, Associate Professor
Dep. Medical Oncology, Bern University Hospital
Switzerland: Independent Local Research Ethic Commission (Ethikkommission)