Non-interventional Study on Salvage Auto in Relapsed Myeloma
Condition: Relapsed Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Study type: Observational

Summary: 
      Multiple myeloma (MM) is an incurable disease that is characterized by the accumulation of
      clonal plasma cells in the bone marrow. While MM patients with relapsed disease may achieve
      responses to subsequent antimyeloma therapies, the duration of response decreases with
      successive relapses until resistant disease develops. Until recently, the median survival
      following relapse after induction therapy was approximately one year. The relatively recent
      US Food and Drug Administration (FDA) approvals of bortezomib (2003) and combination
      lenalidomide plus dexamethasone (2006) therapies for the treatment of previously treated MM
      has provided effective therapeutic options that give patients with relapsed or refractory MM
      the prospect for a prolongation of overall and progression-free survival times. However, MM
      remains an incurable disease. A clear unmet medical need still exists for additional novel
      therapeutic options for the treatment of previously treated MM.

      Plerixafor reversibly inhibits CXCR4 binding to stromal cell derived factor (SDF)-1alpha and
      was recently discovered to be an effective agent to mobilize CD34+ cells into the peripheral
      blood. In normal volunteers, administering Plerixafor after 4-5 days of G-CSF resulted in a
      3-3.5 fold increase in circulating CD34+ cells. Two phases 3 studies demonstrated that the
      combination of G-CSF and Plerixafor is superior to G-CSF alone for mobilizing hematopoietic
      progenitor cells in front-line or as salvage therapy in patients with multiple myeloma.

      Nevertheless, almost all patients ultimately relapse, and no plateau is observed in the
      survival curves. At the time of disease recurrence, there is not one standard salvage
      approach, but instead, various therapeutic options are available, including novel
      agents-based therapy, administered for a fixed duration of time or until progression. In the
      pivotal trial for the approval of bortezomib as monotherapy in relapsed and refractory MM,
      the median PFS was 7 months, whereas in the pivotal trials for the approval of lenalidomide
      in combination with dexamethasone in the same group of patients, the median time to
      progression was approximately 11 months. A more recent prospective, randomized, phase 3 study
      has shown that a triplet combination of bortezomib, thalidomide and dexamethasone (VTD)
      achieved superior results compared to thalidomide dexamethasone (TD) alone in patients
      relapsing following ASCT, with a median time to progression of 19.5 versus 13.8 months,
      respectively. This study suggests that combinations consisting of both an IMiD and a
      proteasome inhibitor are a valuable option at the time of relapse.

      However, when a frozen graft is available, it is also possible to repeat high-dose therapy in
      patients who previously responded to the frontline application of high-dose melphalan and
      ASCT. Over time, several reports have demonstrated the feasibility of this salvage strategy.
      The majority of data are available from retrospective studies and are based on single-centre
      experiences with small numbers of selected patients. In this setting, PFS has been shown to
      range from 7 to 22 months, and the treatment-related mortality (TRM) was acceptable, ranging
      from 0 to 8%. Various prognostic factors for prolonged PFS have been described, such as the
      duration of response to the first high-dose therapy, or the number of lines of therapy prior
      to salvage ASCT.

      With this background, this prospective non-interventional multicentre study will aim to
      collect data on the feasibility of salvage ASCT using a Plerixafor-based stem cell
      mobilization in relapsed MM, according to Plerixafor label in France.

      This is a non-interventional study; visit will be performed as usual, according to each
      center practices. No additional visits will be requested for the study purpose. The date for
      each visit and any data generated must be recorded on the appropriate eCRF.

      The study will consist of 3 periods:

        -  An early screening period

        -  Autologous stem cell mobilization period

        -  High dose melphalan therapy and autologous graft infusion and follow-up for12 months
           after salvage ASCT Inclusion visit

      This visit may occur up to 28 days before Mozobil® administration. This visit will be
      performed during the visit of pre-transplant assessment. For the pre-transplant assessment,
      the procedures are performed routinely before ASCT even if the patient is not included in the
      study:

      Stem cell mobilization phase The stem cell mobilization phase is performed according to
      standard practice of each participating centre.

      Follow-up visits High dose melphalan administration and autologous graft infusion will be
      performed according to each centre standard practice. Patients will be followed according to
      each center practices. The follow-up of this non-interventional study will end 12 months
      after ASCT.

      Subjects will be enrolled over a 2 years period. The total duration of the study will be 36
      months
    


Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Relapsed multiple myeloma patients will be recruited in sites from the French collaborative
        IFM group in France
      
Keywords: Multiple myeloma; ASCT; plerixafor; stem cell mobilization; Salvage ASCT using plerixafor-based stem cell mobilization in relapsed multiple myeloma