Lenalidomide After Reduced-intensity Allogeneic Stem Cell Transplantation for Relapsed Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Study type: Interventional
Phase: Phase 1

Summary: 
      Allogeneic stem cell transplantation (Allo-SCT) in multiple myeloma (MM) remains a
      controversial topic because of a high risk of relapse and a significant transplant-related
      mortality (TRM). In an effort to reduce the TRM, most allogeneic transplants in MM are now
      performed after reduced-intensity conditioning regimens. In these conditions, TRM usually
      range from 10 to 20%. However, reducing the intensity of the conditioning invariably
      increases the incidence of relapse to 45 to 60%. As a consequence, post-transplant strategies
      to reduce the incidence of relapse after reduced-intensity Allo-SCT should be considered and
      evaluated.
    

Detailed description: 
      Lenalidomide has a significant clinical activity in patients with relapsed or refractory MM
      and in patients relapsing after Allo-SCT. The mechanisms of action involve immunomodulation,
      anti-angiogenesis activity, direct anti tumor activity and effects on microenvironment. So
      far, the experience with lenalidomide after Allo-SCT has been limited to patients with
      progressive disease. In such patients, some responses are observed but most of them are
      transient with median progression-free survivals of less than one year. Lenalidomide used as
      maintenance therapy in patients with persistent rather than progressive disease might be a
      better approach.

      Lenalidomide is interesting in the Allo-SCT setting also because some recent studies focusing
      on its immunological properties have suggested that the molecule could stimulate the graft
      versus myeloma effect. First, it has been demonstrated in vitro that lenalidomide can inhibit
      the proliferation and the suppressor function of regulatory T cells. Secondly, a clinical
      study using lenalidomide as salvage therapy after Allo-SCT demonstrated an increase of
      activated T cells and NK cells. Finally, a case report described a patient's response to
      lenalidomide associated with the development of an acute graft versus host disease.

      Taken together, these data suggest that patients with MM who have a persistent disease after
      a reduced-intensity Allo-SCT might benefit from a post-transplant maintenance strategy with
      lenalidomide by a direct anti-tumor effect and a stimulation of the graft versus myeloma
      effect. The primary objective of this study is to evaluate the safety of such a strategy.
    

Intervention name(s): Lenalidomide
Intervention type(s): Drug
Intervention description(s): Start between Day+100 and Day+120 post-transplant
- Initial dose: 5 mg/day every day
In the absence of thrombocytopenia < 75000/mm3 or neutropenia < 1000/mm3 (with or without G-CSF), increase to the upper level than the ongoing one every third month up to the maximal dose of 15 mg/day every day.
- Duration
until persistent stringent complete response for 3 months
or progression defined by IMWG criteria12
or unacceptable toxicity
or one year after transplant
Intervention MeSH terms: Lenalidomide
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: lenalidomide