A Pilot Study of Lenalidomide, Melphalan and Dexamethasone in AL Amyloidosis

The study will evaluate the 3-drug combination of lenalidomide; melphalan; and dexamethasone (MDR) as the absence of disease progression or toxicity, patients will complete nine 28-day cycles of MDR therapy, with the option of continuing treatment with lenalidomide as single-agent. Patients received up to nine cycles of treatment, with the option to continue on lenalidomide as a single agent if they responded to treatment.

Inclusion criteria

• Newly diagnosed or relapsed AL amyloidosis
• Biopsy-proven amyloidosis with evidence of an underlying plasma cell dyscrasia

• abnormal clonal dominance of plasma cells in the bone marrow
• detection of a monoclonal gammopathy by immunofixation electrophoresis of serum and/or urine
• an abnormal serum free light chain or ratio, or AL fibrils seen on biopsy)
• Measurable disease defined by an abnormal serum-free light chain or monoclonal protein by immunofixation

• proteinuria ≥ 0.5 g/day, cardiac involvement with interventricular septal thickness ≥ 15 mm
• hepatomegaly in the absence of congestive heart failure with elevated alkaline phosphatase
• Age ≥ 18 years at the time of signing the informed consent form.
• All previous cancer therapy must have been discontinued at least 4 weeks prior to treatment in this study
• ECOG performance status of ≤ 3 at study entry
• Laboratory test results:

• Absolute neutrophil count ≥ 1.0 x 10e9 / L
• Platelet count ≥ 75 x 10e9 / L
• Creatinine clearance ≥ 15 mL/ minute
• Total bilirubin ≤ 2-fold upper limits of normal
• Disease-free of prior malignancies (excluding multiple myeloma) for ≥ 3 years with exception of:

• currently treated basal cell
• squamous cell carcinoma of the skin
• carcinoma "in situ" of the cervix or breast.
• Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test
• Females of childbearing potential must either:

• commit to continued abstinence from heterosexual intercourse
• acceptable methods of birth control and agree to ongoing pregnancy testing
• Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy
• All study participants must be registered into the mandatory RevAssist program, and able to comply with its requirements
• Able to take aspirin (81 mg) daily • Understand and voluntarily sign an informed consent form
• Able to adhere to the study visit schedule and other protocol requirements

Exclusion criteria

• Any serious medical condition that would prevent the subject from signing the informed consent form
• Pregnant
• breast-feeding females
• Use of any other experimental drug or therapy within 28 days of baseline
• Known hypersensitivity to thalidomide
• Erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs
• Any prior use of lenalidomide
• Concurrent use of other anti-cancer agents or treatments
• Known positivity for human immunodeficiency virus HIV)