PAV-trial: Plerixafor and Chemotherapy With Vinorelbine for Stem Cell Mobilization in Patients With Myeloma
Condition: Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

Detailed description: 
      Background

      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.

      Objective

      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.

      Methods

      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.
    

Intervention name(s): Vinorelbine, G-CSF, & Plerixafor; Vinorelbine and Plerixafor; G-CSF and Plerixafor; Vinorelbine & Plerixafor on day when CD34 count is at least 15'000 CD34+ cells/ml of peripheral blood
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Patients 1-10 receive 35 mg/m2 vinorelbine i.v. on day 1, G-CSF divided in two daily doses from day 4 until collection of stem cells, and plerixafor 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.; Patients 11-20 receive 35 mg/m2 vinorelbine i.v. on day 1 and plerixafor as an i.v. application on day 8, at 08:00 AM, in the dose of 240 microg/kg b.w. No G-CSF will be administered. 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.; Patients 21-30 receive G-CSF divided in two daily doses from day 4 until collection of stem cells, and plerixafor as an i.v. application on day 8, at 08:00 AM, in the dose of 240 microg/kg b.w. No chemotherapy with vinorelbine will be gine on day 1. 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.; Patients 31-40 receive 35 mg/m2 vinorelbine i.v. on day 1 and plerixafor as an i.v. application at 08:00 AM, on the first day on which the CD34 count has risen to at least 15'000 CD34+ cells/ml of peripheral blood. Stem cell collection is initiated 4 hours later (at 12:00 PM) on this day. No G-CSF will be administered.
Intervention MeSH terms: Plerixafor; Vinorelbine; Lenograstim
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Mobilization of autologous peripheral blood progenitor cells PBPC; Autologous stem cell mobilization; Multiple Myeloma; Plerixafor