Inclusion Criteria:

- Diagnosis of multiple myeloma (MM)

- Salmon-Durie stage IIA or IIIA

- No stage B disease

- Meets ≥ 1 major AND 1 minor criterion OR ≥ 3 minor criteria

- The following are considered major criteria:

- Plasmacytoma on tissue biopsy

- Bone marrow plasmacytosis with ≥ 30% plasma cells

- Monoclonal paraprotein ≥ 3,500 mg/dL (IgG) or ≥ 2,000 mg/dL (IgA) OR
monoclonal protein (Bence-Jones protein) ≥ 1,000 mg by 24-hour urine
collection

- The following are considered minor criteria:

- Bone marrow plasmacytosis 10-29% of marrow cellularity

- Monoclonal globulin spike < 3,500 mg/dL (IgG) or < 2,000 mg/dL (IgA)

- Lytic bone lesions

- Decrease in normal IgM (< 50 mg/dL), IgA (< 100 mg/dL), or IgG (< 600
mg/dL)

- Disease progression after ≥ 1 prior systemic treatment regimen* for MM (e.g.,
chemotherapy, high-dose corticosteroids, thalidomide, or bortezomib), defined as >
25% increase in serum or urine M-protein

- No solitary plasmacytoma

- No non-secretory MM (absent serum or urinary M-protein)

- ECOG performance status 0-2

- Life expectancy > 6 months

- Bilirubin ≤ 1.5 times upper limit of normal (ULN)

- AST and ALT ≤ 3 times ULN

- Creatinine ≤ 2.0 mg/dL

- Absolute neutrophil count ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Fasting cholesterol ≤ 350 mg/dL

- Fasting triglycerides ≤ 400 mg/dL

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective double-method contraception

- Must agree not to donate blood, sperm, or ova during and for 4 weeks after completion
of study treatment

- No other prior or concurrent malignancy or myelodysplasia except for the following:

- Basal cell or squamous cell skin cancer

- Carcinoma in situ of the cervix

- Localized cancer treated with surgery only with no evidence of disease for > 5
years

- No history of recurrent deep vein thrombosis (DVT)/pulmonary embolism (PE) or DVT/PE
occurring while on therapeutic levels of anticoagulation

- Patients with DVT/PE within the past 6 months are eligible provided they receive
full anticoagulation during study treatment

- No active infection requiring oral or intravenous antibiotics

- No uncontrolled illness including, but not limited to, any of the following:

- Ongoing or active infection

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiac arrhythmia

- Psychiatric illness or social situations that would preclude study compliance

- No known hepatitis B or C

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to lenalidomide or CCI-779

- See Disease Characteristics

- Prior lenalidomide allowed

- Prior high-dose chemotherapy with stem cell transplantation allowed

- More than 4 weeks since prior chemotherapy or other antimyeloma systemic therapy
(e.g., thalidomide, bortezomib, or high-dose corticosteroids) and recovered

- No prior exposure to both lenalidomide and mTOR inhibitors (given together)

- Treatment with single-agent lenalidomide or single-agent mTOR inhibitor allowed

- No other concurrent investigational agents

- No concurrent corticosteroids unless for physiologic maintenance

- No concurrent antiretroviral therapy for HIV-positive patients

- No concurrent myeloid growth factors (e.g., filgrastim [G-CSF] or sargramostim
[GM-CSF])

- No concurrent grapefruit or grapefruit juice