RATIONALE: Biological therapies, such as CC-4047, may stimulate the immune system in different ways and stop cancer cells from growing. Dexamethasone and CC-4047 may stop the growth of cancer cells by blocking blood flow to the cancer. Giving CC-4047 together with dexamethasone may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving CC-4047 together with dexamethasone works in treating patients with relapsed or refractory multiple myeloma or amyloidosis.

OBJECTIVES:

• To assess the response rate and duration of remission with low-dose CC-4047 plus dexamethasone in patients with relapsed or refractory multiple myeloma or amyloidosis.
• To assess the toxicity of CC-4047 plus dexamethasone in this patient population.
• To assess in an expansion cohort the response rate with an increase in CC-4047 dose among patients who fail to respond adequately to the initial starting dose following the first 2 courses of treatment.
• To assess the response rate and duration of remission with CC-4047 plus dexamethasone in patients with lenalidomide resistant or refractory multiple myeloma.
• To assess the response rate and duration of remission with CC-4047 plus dexamethasone in patients with previously treated light chain amyloidosis.
• To assess the response rate and duration of remission with low- and high-dose CC-4047 plus dexamethasone in patients with lenalidomide and bortezomib refractory multiple myeloma.
• To assess the response rate and duration of remission with high-dose CC-4047 plus dexamethasone in patients with relapsed or refractory myeloma who received ≤ 3 treatment regimens.

OUTLINE: Patients are grouped according to disease status (relapsed/refractory myeloma [closed to accrual as of 8/5/2008] vs lenalidomide resistant/refractory myeloma [closed to accrual as of 4/2/2009] vs previously treated light chain amyloidosis vs lenalidomide and bortezomib resistant/refractory myeloma {low-dose/day}[closed to accrual as of 11/20/09] vs lenalidomide and bortezomib resistant/refractory myeloma (high-dose/day) vs relapsed/refractory myeloma {high-dose/day}).

Patients receive oral CC-4047 on days 1-28 and oral dexamethasone on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for 4 weeks and then at 6 months.

DISEASE CHARACTERISTICS:

• Symptomatic multiple myeloma

• Previously treated disease meeting one of the following criteria:

  • Have light-chain amyloidosis that has been treated with at least one prior regimen

  • Symptomatic (relapsed or refractory) multiple myeloma

    • Patients must have received 1-3 treatment regimens
    • Induction therapy followed by autologous stem cell transplantation and consolidation considered one regimen

• Measurable disease, as defined by 1 of the following:

  • Serum monoclonal protein ≥ 1.0 g by protein electrophoresis
  • More than 200 mg of monoclonal protein in the urine on 24-hour electrophoresis
  • Serum immunoglobulin free light chain (FLC) > 10 mg/dL and an abnormal FLC ratio
  • Measurable soft tissue plasmacytoma, not previously irradiated
  • More than 30% plasma cells in bone marrow

• At least 10% plasma cells as measured by bone marrow aspirate, bone marrow biopsy, or labeling index

• No monoclonal gammopathy of undetermined significance (not applicable for patients with amyloid)

• No smoldering myeloma (not applicable for patients with amyloid)

PATIENT CHARACTERISTICS:

• ECOG performance status 0, 1, or 2

• ANC ≥ 1,000/μL

• Platelet count ≥ 75,000/μL

• Creatinine ≤ 2.5 mg/dL

• Not pregnant or nursing

  • Women must refrain from breastfeeding during study participation and for at least 28 days after discontinuation of study drug

• Negative pregnancy test

• Fertile female patients must use two reliable forms of contraception simultaneously at least 28 days before beginning, during, and at least 28 days after completion of study drug

  • The two methods of reliable contraception must include one highly effective method (i.e., intrauterine device [IUD], hormonal [birth control pills, injections, or implants], tubal ligation, or partner's vasectomy) and one additional effective (barrier) method (i.e., latex condom, diaphragm, or cervical cap)

• Fertile male patients must use a latex condom (even if they have undergone a prior vasectomy) while having intercourse with any woman, while taking the drug and for 28 days after stopping treatment

• Men must agree to abstain from donating semen or sperm during study participation and for 28 days after discontinuation of study drug

• Willing to abstain from donating blood during study participation and for 28 days after discontinuation of study drug

• No uncontrolled infection

• No other active malignancy

• No New York Heart Association class III or IV cardiac disease (all patients)

  • Serum troponin T > 0.10 ng/mL (amyloid patients only)

• No known positivity for HIV or active hepatitis infection

• No active deep vein thrombosis or pulmonary embolism that has not been therapeutically anticoagulated

• No condition, including the presence of laboratory abnormalities, that places the patient at unacceptable risk for participating in the study or confounds the ability to interpret data from the study

• No known hypersensitivity to thalidomide or lenalidomide including development of erythema nodosum if characterized by a desquamating rash

• No peripheral neuropathy > grade 2

PRIOR CONCURRENT THERAPY:

• All previous cancer therapy, including chemotherapy and investigational agents, must have been discontinued ≥ 2 weeks prior to study registration
• No radiotherapy ≤ 14 days prior to study registration
• No other concurrent anti-myeloma therapy
• No concurrent radiotherapy, except for palliation of a single painful bone lesion or fracture
• Routine concurrent bisphosphonate therapy allowed for patients with myeloma bone disease
• Willing and able to take aspirin or alternate prophylactic anticoagulation

One participant in the Relapse/Refractory Myeloma: High Dose group refused prior to starting treatment, thus was not included in the adverse event analysis.