NCT00621400

Lenalidomide in Combination With Melphalan and Dexamethasone in Newly-diagnosed Light-chain (AL)-Amyloidosis

A Multicenter Phase I/II Dose Escalation Study of Lenalidomide in Combination With Melphalan and Dexamethasone in Subjects With Newly-diagnosed Light-chain (AL)-Amyloidosis

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 27 (actual)
• Sponsor: Nantes University Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Amyloidosis

Interventions

Type	Name	Description
DRUG	Lenalidomide	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
DRUG	Melphalan	0,18mg/Kg/day from day 1- 4
DRUG	Dexamethasone	40mg/day from day 1- 4.

Timeline

• Start date: 2008-01-01
• Primary completion: 2009-12-01
• Completion: 2009-12-01
• First posted: 2008-02-22
• Last updated: 2011-05-10

Locations

12 sites across 1 country: France