Lenalidomide and Dexamethasone With/Without Stem Cell Transplant in Patients With Multiple Myeloma

Multiple myeloma is a malignant plasma cell proliferative disorder responsible for 11, 000
deaths each year in the United States. Approximately one third of myeloma patients develop
hypercalcemia and about two thirds present with anemia. As the second most common hematologic
malignancy, myeloma remains incurable. In the last forty years, options for therapy have
included melphalan-prednisone, anthracyclines, and vinca alkaloids; however, relapse with
those regimens continues to be inevitable with a median survival of 3 years.

Inclusion Criteria:

- Histologically or cytologically confirmed Multiple Myeloma, Salmon-Durie Stage II or
III or International Staging System II or III that has not been previously treated.

- Bone marrow plasmacytosis with > or = 10% plasma cells, or sheets of plasma cells or a
biopsy-proven plasmacytoma.

- Measurable levels of monoclonal protein (M protein): 1 g/dL IgG or .5 g/dL IgA on
serum protein electrophoresis or > 200 mg of monoclonal light chain on a 24 hour urine
protein electrophoresis.

- Age > or = 18 years.

- Life expectancy of greater than 12 months.

- ECOG performance status < or = 2 (Karnofsky > or = 60%).

- Adequate organ and marrow function as defined below:

- Hgb > or = 9 g/dL

- Absolute Neutrophil Count > or = 1,500/ ml

- Platelets > or = 50,000/mm3

- Total Bilirubin < or = 1.5 mg/dL

- AST(SGOT) / ALT(SGPT) < or = 2.5 X ULN

- Creatinine < 2.0 mg/dL

- Creatinine Clearance > or = 50 ml/min

- Registered into the mandatory Revlimid REMS® program, and be willing and able to
comply with the requirements of the REMS® program.

- Females of reproductive potential must adhere to the scheduled pregnancy testing as
required in the Revlimid REMS® program.

- Ability to understand and the willingness to sign a written informed consent document.

- Subjects with a history of prior malignancy are eligible provided there is no active
malignancy and a low expectation of recurrence within 6 months.

- Must be willing and able to take prophylaxis with either aspirin at 81 mg/day or
alternative prophylaxis with either low molecular weight heparin or warfarin as
recommended.

- Eligible for transplant with an age up to and including 75 years.

- Subjects in ARM A who are refusing transplant can go onto ARM B and will be evaluated
separately.

- Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy
test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again
within 24 hours of prescribing lenalidomide and must either commit to continued
abstinence or TWO acceptable methods of birth control. FCBP must also agree to ongoing
pregnancy testing. Males must agree to use a latex condom.

Exclusion Criteria:

- Have had chemotherapy or radiotherapy for multiple myeloma within 4 weeks of baseline.

- Receiving any other investigational agents or therapy within 28 days of baseline.

- Brain metastases.

- Subjects who are pregnant or breast feeding.

- History of previous deep vein thrombosis or pulmonary embolism must be on
anticoagulation therapy with low molecular weight heparin or warfarin at therapeutic
dosages (e.g. INR 2-3).

- If a subject is on full-dose anticoagulants, the following criteria should be met for
enrollment:

- Must not have active bleeding or pathological conditions that carry high risk of
bleeding (e.g. tumor involving major vessels, known varices).

- Must not have thrombocytopenia requiring transfusion.

- Must have a platelet count > 50,000.

- Must have stable INR between 2-3.

- Smoldering myeloma or monoclonal gammopathy of undetermined significance.

- Active, uncontrolled infection.

- Active, uncontrolled seizure disorder (seizures in the last 6 months).

- Concurrent use of other anti-cancer agents or treatments.

- Positive for HIV or infectious hepatitis, type B or C.

- Hypersensitivity to thalidomide.

- Any condition, including the presence of laboratory abnormalities, which places the
subject at unacceptable risk.