Clinical Trial: Lenalidomide, Dexamethasone and Cyclophosphamide in Amyloidosis (AL)

Study Status: Active, not recruiting
Recruit Status: Unknown status
Study Type: Interventional

Official Title: A Phase I/II Trial of Lenalidomide Combined With Cyclophosphamide and Intermediate Dose Dexamethasone in Patients With Primary (AL) Systemic Amyloidosis

Brief Summary: The purpose of this study is to determine the safety and activity of the combination of lenalidomide with intermediate dose dexamethasone and cyclophosphamide in patients with primary systemic (AL ) amyloidosis.

Detailed Summary: Primary systemic amyloidosis (AL) is a plasma cell dyscrasia where amyloid fibrils are formed by monoclonal immunoglobulin light chains and deposit in various organs causing tissue damage and dysfunction. It is a rare disease with an incidence of 8 patients per million per year. Virtually all patients die of this disease with a median survival of 12-18 months and less than approximately 5% surviving 10 years. The current therapeutic approach to systemic amyloidosis is based on the observation that amyloid deposits can be reabsorbed and organ function can be restored if the concentration of the amyloidogenic precursor is reduced. The recognized standard treatment for patients with amyloidosis is alkylating agent-based chemotherapy - some selected patients can be treated with high dose melphalan with autologous stem cell transplantation. Recent studies have led to an improved understanding of the biology of plasma cells. Interactions between the bone marrow microenvironment and plasma cells have a critical growth regulating influence on myeloma cells. Thalidomide has shown significant activity in multiple myeloma patients with relapsing or refractory disease and even more in newly diagnosed patients. However, thalidomide causes somnolence, fatigue, constipation, and peripheral neuropathy and is not well tolerated in patients with AL amyloidosis. Lenalidomide is a small molecule structurally related to thalidomide with potent immunomodulatory effects. Lenalidomide has been found to be significantly active in relapsed multiple myeloma both in vitro and in Phase I, II and III clinical trials, including patients who had previously failed thalidomide. Unlike thalidomide, lenalidomide causes no significant sedation, constipation, neuropathy, or rash. Deep vein thrombosis ,especially in combination with dexamethasone, has been reported . Combination of thalidomide with with alkylating agents (such as melphalan or cyclophosphamide) have been very active in patients with myelo
Sponsor: University of Athens

Current Primary Outcome: To assess the maximum tolerated dose of lenalidomide and cyclophosphamide and assess the hematologic response rate of the combination of Cyclophosphamide/Dexamethasone plus lenalidomide in patients with AL amyloidosis. [ Time Frame: At month 2 for assesment of maximum tolerated dose and monthly for hematologic response ]

Original Primary Outcome: Same as current

Current Secondary Outcome: To assess the toxicity of Cyclophosphamide/Dexamethasone plus lenalidomide combination in patients with AL amyloidosis and organ response rate [ Time Frame: Monthly for toxicity and every 3-6 months for organ response ]

Original Secondary Outcome: Same as current

Information By: University of Athens

Dates:
Date Received: September 19, 2009
Date Started: February 2008
Date Completion: February 2015
Last Updated: January 30, 2014
Last Verified: January 2014