PAV-trial: Plerixafor and Chemotherapy With Vinorelbine for Stem Cell Mobilization in Patients With Myeloma
Recruitment status was Recruiting
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. In this trial the intravenous application of Plerixafor is being investigated in respect of the capability of the mobilization of stem cells from the bone marrow into the peripheral blood. In contrast to the twice daily application of G-CSF (eg. Neupogen) for several days, Plerixafor has to be injected just one-time.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||PAV-trial: Plerixafor and Chemotherapy With Vinorelbine for Stem Cell Mobilization in Patients With Myeloma. A Pilot Phase II Study.|
- Number of CD34+ peripheral blood stem cells/kg [ Time Frame: day 8 (and 9, if necessary) ] [ Designated as safety issue: No ]
- Incidence and severity of adverse events during and after the use of plerixafor [ Time Frame: 15 days ] [ Designated as safety issue: Yes ]
- Proportion of patients with engraftment of PBPC defined as an ANC recovery of ≥ 0.5 x 109/L for 3 consecutive days and a platelet recovery of ≥ 20 x 109/L in the absence of platelet transfusion for at least 7 days [ Time Frame: 21 months ] [ Designated as safety issue: Yes ]
- Comparison of costs for mobilization of PBPC with vinorelbine and plerixafor versus the costs for mobilization with vinorelbine and filgrastim and versus the costs for mobilization with vinorelbine and pegfilgrastim [ Time Frame: 21 Months ] [ Designated as safety issue: No ]
|Study Start Date:||April 2010|
|Estimated Study Completion Date:||December 2011|
|Estimated Primary Completion Date:||December 2011 (Final data collection date for primary outcome measure)|
Plerixafor is a bicyclam with hematopoietic stem cell-mobilizing activity. Plerixafor blocks the binding of stromal cell-derived factor (SDF-1alpha) to the cellular receptor CXCR4, resulting in hematopoietic stem cell release from bone marrow and HSC movement into the peripheral circulation.
Plerixafor is given as an i.v. application on day 8, at 08:00 AM, in the dose of 240 microg/kg b.w. Stem cell collection is initiated 4 hours later (at 12:00 PM) at day 8, if at least 20 X 103 of CD34+ cells / ml peripheral blood are detected.
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 application.
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.
|Dep. of Medical Oncology, Bern University Hospital||Recruiting|
|Bern, Switzerland, 3010|
|Contact: Stephan Schobinger, MD +41 31 632 21 11 email@example.com|
|Contact: Anke Klingenberg, Stucy Nurse +41 31 632 21 11 Anke.Klingenberg-Rettich@insel.ch|
|Principal Investigator: Thomas Pabst, Associate Professor|
|Principal Investigator:||Thomas Pabst, Associate Professor||Dep. Medical Oncology, Bern University Hospital|