Velcade,Thalidomide, and Dexamethasone Versus Velcade and Dexamethasone Versus Velcade, Melphalan, and Prednisone

Inclusion Criteria:

• Male or female 18 years of age or older

• Not a candidate for high-dose chemotherapy and stem cell transplantation (HDT/SCT) dueto age, presence of important comorbid condition(s) likely to have a negative impacton tolerability of HDT-SCT, or subject preference.

• A Karnofsky Performance Status score of ≥50%

• Symptomatic multiple myeloma or asymptomatic multiple myeloma with related organ ortissue damage.

• Asymptomatic multiple myeloma-related organ or tissue damage can include presence ofan asymptomatic lytic bone lesion or plasmacytoma, the presence of anemia (hemoglobin <10 g/dL), renal function impairment (serum creatinine > upper limit of normal [ULN])or hypercalcemia (serum calcium >ULN).

• Must have measurable disease requiring systemic therapy. Measurable disease is definedby at least 1 of the following criteria:

• Quantifiable serum M-protein value (>1 g/dL of immunoglobulin (Ig)G or IgMM-protein, >0.5g/dL of IgA M-protein, >0.5 g/dL of IgD M-protein)

• Urine light-chain excretion ≥200 mg/24 hours

• Voluntary written informed consent must be given before performance of any studyrelated procedure not part of normal medical care, with the understanding that consentmay be withdrawn by the participant at any time without prejudice to future medicalcare.

Exclusion Criteria:

• Diagnosis of smoldering multiple myeloma or monoclonal gammopathy of undeterminedsignificance (MGUS). Smoldering multiple myeloma is defined as asymptomatic multiplemyeloma with absence of lytic bone lesions. MGUS is defined by presence of serummonoclonal protein <3 g/dL; absence of lytic bone lesions, anemia, hypercalcemia, andrenal insufficiency related to the monoclonal protein; and (if determined) proportionof plasma cells in the bone marrow of 10% or less.

• Diagnosis of Waldenström's disease or other conditions in which immunoglobulin M (IgM)M-protein is present in the absence of a clonal plasma cell infiltration or lytic bonelesions.

• Previously or currently treated with any systemic therapy for multiple myeloma. Priortreatment of hypercalcemia or spinal cord compression with corticosteroids orradiation therapy, respectively, does not disqualify the subject (the dose ofcorticosteroids should not exceed the equivalent of 160 mg of dexamethasone in 2-weekperiod).

• Radiation therapy within 2 weeks before randomization. Enrollment of patients whorequire concurrent radiotherapy (which must be localized in its field size) should bedeferred until the radiotherapy is completed and 2 weeks have elapsed since the lastdate of therapy.

• Major surgery within 30 days before randomization (Kyphoplasty is not considered majorsurgery)

• History of allergy to any of the study medications, their analogues, or excipients inthe various formulations

• ≥Grade 2 peripheral neuropathy on clinical examination within 21 days beforeenrollment.

• Any of the following clinical laboratory values within 21 days prior to enrollment:

• Absolute neutrophil count (ANC) <1000 cells/mm^3

• Platelets <100,000 × 10^9/L, or <70 × 10^9/L if thrombocytopenia is considered bythe investigator to be due to myeloma infiltration of bone marrow

• Aspartate aminotransferase [serum glutamic oxaloacetic transaminase] (AST [SGOT])or alanine aminotransferase [serum glutamic-pyruvic transaminase] (ALT [SGPT]) >2× the upper limit of normal (ULN)

• Serum creatinine >2 mg/dL (>176.8 µmol/L); if the rise in creatinine is relatedto myeloma and there has been demonstrated a response to hydration, the subjectmay be enrolled.

• Myocardial infarction within 6 months prior to enrollment or New York HospitalAssociation Class III or IV heart failure, uncontrolled angina, severe uncontrolledventricular arrhythmias, or electrocardiographic evidence of acute ischemia orsignificant conduction system abnormalities in the opinion of the investigator. Priorto study entry, any abnormality on electrocardiogram at screening must be determinedand documented by the investigator as not medically relevant.

• Any condition, including laboratory abnormalities, that in the opinion of theInvestigator places the patient at unacceptable risk if he/she were to participate inthe study. This includes but is not limited to serious medical conditions orpsychiatric illness likely to interfere with participation in this clinical study.

• Prior malignancy except for adequately treated basal cell or squamous cell skincancer, in situ cervical cancer, in situ breast cancer, in situ prostate cancer, orother cancer for which the patient has been disease-free for at least 3 years.

• Female who is pregnant or breastfeeding. Female participants of childbearing potentialmust have a negative pregnancy test with a sensitivity of at least 50 mIU/mL duringScreening.

• Use of any investigational drugs within 30 days before randomization.