Study to Determine Efficacy and Safety of Lenalidomide Plus Low-dose Dexamethasone Versus Melphalan, Prednisone, Thalidomide in Patients With Previously Untreated Multiple Myeloma

Inclusion Criteria:

1. Must understand and voluntarily sign informed consent form

2. Age ≥ 18 years at the time of signing consent

3. Previously untreated, symptomatic multiple myeloma as defined by the 3 criteria below:

• MM diagnostic criteria (all 3 required):

• Monoclonal plasma cells in the bone marrow ≥10% and/or presence of abiopsy-proven plasmacytoma

• Monoclonal protein present in the serum and/or urine

• Myeloma-related organ dysfunction (at least one of the following) [C] Calciumelevation in the blood (serum calcium >10.5 mg/dl or upper limit of normal) [R]Renal insufficiency (serum creatinine >2 mg/dl) [A] Anemia (hemoglobin <10 g/dlor 2 g < laboratory normal) [B] Lytic bone lesions or osteoporosis AND have measurable disease by protein electrophoresis analyses as defined by thefollowing:

• IgG multiple myeloma: Serum monoclonal paraprotein (M-protein) level ≥ 1.0 g/dlor urine M-protein level ≥ 200 mg/24 hours

• IgA multiple myeloma: Serum M-protein level ≥ 0.5 g/dl or urine M-protein level ≥ 200 mg/24 hours

• IgM multiple myeloma (IgM M-protein plus lytic bone disease documented byskeletal survey plain films): Serum M-protein level ≥ 1.0 g/dl or urine M-proteinlevel ≥ 200mg/24hours

• IgD multiple myeloma: Serum M-protein level ≥ 0.05 g/dl or urine M-protein level ≥ 200 mg/24 hours

• Light chain multiple myeloma: Serum M-protein level ≥ 1.0 g/dl or urine M-proteinlevel ≥ 200 mg/24 hours AND are at least 65 years of age or older or, if younger than 65 years of age, are notcandidates for stem cell transplantation because:

• The patient declines to undergo stem cell transplantation or

• Stem cell transplantation is not available to the patient due to cost or otherreasons

4. ECOG performance status of 0, 1, or 2

5. Able to adhere to the study visit schedule and other protocol requirements

6. Females of child-bearing potential (FCBP)^2:

7. Must agree to undergo two medically supervised pregnancy tests prior to startingstudy therapy with either Rd or MPT. The first pregnancy test will be performedwithin 10-14 days prior to the start of Rd or MPT and the second pregnancy testwill be performed within 24 hours prior to the start of Rd or MPT. She must alsoagree to ongoing pregnancy testing during the course of the study and after theend of study therapy. This applies even if the patient practices complete andcontinued sexual abstinence.

8. Must commit to either continued abstinence from heterosexual intercourse (whichmust be reviewed on a monthly basis) or agree to use and be able to comply witheffective contraception without interruption, 28 days prior to starting studydrug, during the study therapy (including during periods of dose interruptions),and for 28 days after discontinuation of study therapy.

9. Male Patients:

10. Must agree to use a condom during sexual contact with a FCBP, even if they havehad a vasectomy, throughout study drug therapy, during any dose interruption andafter cessation of study therapy.

11. Must agree to not donate semen during study drug therapy and for a period afterend of study drug therapy.

12. Must practice complete abstinence or agree to use a condom during sexual contactwith a pregnant female or a female of childbearing potential while participatingin the study, during dose interruptions and for at least 28 days following studydrug discontinuation, even if he has undergone a successful vasectomy.

13. All patients must:

14. Have an understanding that the study drug could have a potential teratogenicrisk.

15. Agree to abstain from donating blood while taking study drug therapy andfollowing discontinuation of study drug therapy.

16. Agree not to share study medication with another person. All FCBP and malepatients must be counseled about pregnancy precautions and risks of fetalexposure.

Exclusion Criteria:

1. Previous treatment with anti-myeloma therapy (does not include radiotherapy,bisphosphonates, or a single short course of steroid [i.e., less than or equal to theequivalent of dexamethasone 40 mg/day for 4 days; such a short course of steroidtreatment must not have been given within 14 days of randomization]).

2. Any serious medical condition that places the patient at an unacceptable risk if he orshe participates in this study. Examples of such a medical condition are, but are notlimited to, patient with unstable cardiac disease as defined by: Cardiac events suchas MI within the past 6 months, NYHA heart failure class III-IV, uncontrolled atrialfibrillation or hypertension; patients with conditions requiring chronic steroid orimmunosuppressive treatment, such as rheumatoid arthritis, multiple sclerosis andlupus, that likely need additional steroid or immunosuppressive treatments in additionto the study treatment.

3. Pregnant or lactating females.

4. Any of the following laboratory abnormalities:

• Absolute neutrophil count (ANC) < 1,000/µL (1.0 x 109/L)

• Untransfused platelet count < 50,000 cells/µL (50 x 10^9/L)

• Serum SGOT/AST or SGPT/ALT > 3.0 x upper limit of normal (ULN)

5. Renal failure requiring hemodialysis or peritoneal dialysis.

6. Prior history of malignancies, other than multiple myeloma, unless the patient hasbeen free of the disease for ≥ 3 years. Exceptions include the following:

• Basal cell carcinoma of the skin

• Squamous cell carcinoma of the skin

• Carcinoma in situ of the cervix

• Carcinoma in situ of the breast

• Incidental histological finding of prostate cancer (TNM stage of T1a or T1b)

7. Patients who are unable or unwilling to undergo antithrombotic therapy.

8. Peripheral neuropathy of > grade 2 severity.

9. Known HIV positivity or active infectious hepatitis, type A, B, or C. Primary AL (immunoglobulin light chain) amyloidosis and myeloma complicated by amyloidosis.

• 1 A variety of other types of end organ dysfunctions can occasionally occur andlead to a need for therapy. Such dysfunction is sufficient to supportclassification as myeloma if proven to be myeloma-related.

• 2 A FCBP is a sexually mature woman who: 1) has not undergone a hysterectomy orbilateral oophorectomy or 2) has not been naturally postmenopausal (i.e.,amenorrhea following cancer therapy does not rule out childbearing potential) forat least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).