Lenalidomide in Combination With Melphalan and Dexamethasone in Newly-diagnosed Light-chain (AL)-Amyloidosis
Condition: Amyloidosis
MeSH terms: Amyloidosis
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Amyloidosis results from tissue deposition of amyloid protein, composed mainly by the
      fragments of monoclonal immunoglobulin heavy chains or light chains. Accumulation of amyloid
      protein progressively disrupts normal tissue structure and ultimately leads to organ failure,
      most frequently in the kidneys, heart, liver and peripheral nervous system. A recently
      completed French prospective randomized trial, in patients presenting with newly
      AL-amyloidosis, compared two treatment regimens at the time of diagnosis:
      Melphalan-dexamethasone (conventional oral treatment), versus high dose of Melphalan followed
      by autologous stem cell transplantation (ASCT) (1). High-dose therapy was not associated with
      a better outcome. Melphalan-dex given monthly can be considered as the current standard of
      care, with a median survival of 56 months. The use of a combination of lenalidomide and
      dexamethasone has already been tested in patients with AL-amyloidosis (2). The initial dose
      of lenalidomide at 25 mg/day was poorly tolerated. However, a 15 mg/day dose regimen was well
      tolerated and effective, with an overall hematologic response rate of 67%. Hematologic
      responses were associated with clinical responses. Dispenzieri et al confirmed that the
      combination of Lenalidomide + dexamethasone achieved a 75% hematologic response rate, with a
      42% organ response, and a median follow-up of 17 months in patients still receiving treatment
      (2006). These authors also recommended a lower dose of 15mg/day. The rationale for the
      present investigation is that addition of lenalidomide to the current standard of care
      (Melphalan-dexamethasone) might improve the hematologic response rate and the organ response
      rates both associated with a prolonged survival in patients with AL-amyloidosis. As the
      toxicity of the combination of M-dex + lenalidomide is unknown in patients with
      AL-amyloidosis, the dose of lenalidomide will start from the lowest one available, i.e., 5
      mg/day and increased from 5 to 5 mg up to a maximum dose of 15 mg in combination with M-dex
      in 3 consecutive cohorts of patients, according to toxicity. When the optimal dose of
      lenalidomide will be defined, 9 additional patients will be included in the trial at the
      recommended dose-level to assess the feasibility of the combination M-dex-lenalidomide.
    


Intervention name(s): Lenalidomide; Melphalan; Dexamethasone
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 5 mg/day, orally for 21 days with 7 days rest (28 day cycle) for the first cohort; or 10mg/day, orally for 21 days with 7 days rest (28 day cycle) for the second cohort, 15mg/day, orally for 21 days with 7 days rest (28 day cycle) for the third cohort or 20mg/day, orally for 21 days with 7 days rest (28 day cycle) for the last and fourth cohort; 0,18mg/Kg/day from day 1- 4; 40mg/day from day 1- 4.
Other intervention name(s): Revlimid; Alkeran
Intervention MeSH terms: Dexamethasone; Lenalidomide; Melphalan
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: newly-diagnosed light-chain (AL)-amyloidosis