This open-label trial will evaluate the use of lenalidomide; melphalan; and dexamethasone (MDR) to treat newly diagnosed or relapsed AL amyloidosis, over the course of nine 28-day cycles.

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)

Lenalidomide-naïve adults with biopsy-proven amyloidosis manifested as measurable disease, ECOG ≤ 3

12 months