Lenalidomide in Combination With Melphalan and Dexamethasone in Newly-diagnosed Light-chain (AL)-Amyloidosis
Status:
Completed
Trial end date:
2009-12-01
Target enrollment:
Participant gender:
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.