Velcade,Thalidomide, and Dexamethasone Versus Velcade and Dexamethasone Versus Velcade, Melphalan, and Prednisone
Velcade,Thalidomide, and Dexamethasone Versus Velcade and Dexamethasone Versus Velcade, Melphalan, and Prednisone
This is a randomized, open label, multicenter clinical trial to compare the efficacy and
 safety of Velcade (bortezomib) and dexamethasone versus Velcade, thalidomide, and
 dexamethasone versus Velcade, melphalan, and prednisone in patients with previously untreated
 multiple myeloma not considered candidates for high-dose chemotherapy and autologous stem
 cell transplantation.
Inclusion Criteria:

 -  Male or female 18 years of age or older

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

 -  A Karnofsky Performance Status score of ≥50%

 -  Symptomatic multiple myeloma or asymptomatic multiple myeloma with related organ or
 tissue damage.

 -  Asymptomatic multiple myeloma-related organ or tissue damage can include presence of
 an 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 defined
 by at least 1 of the following criteria:

 -  Quantifiable serum M-protein value (>1 g/dL of immunoglobulin (Ig)G or IgM
 M-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 study
 related procedure not part of normal medical care, with the understanding that consent
 may be withdrawn by the participant at any time without prejudice to future medical
 care.

 Exclusion Criteria:

 -  Diagnosis of smoldering multiple myeloma or monoclonal gammopathy of undetermined
 significance (MGUS). Smoldering multiple myeloma is defined as asymptomatic multiple
 myeloma with absence of lytic bone lesions. MGUS is defined by presence of serum
 monoclonal protein <3 g/dL; absence of lytic bone lesions, anemia, hypercalcemia, and
 renal insufficiency related to the monoclonal protein; and (if determined) proportion
 of 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 bone
 lesions.

 -  Previously or currently treated with any systemic therapy for multiple myeloma. Prior
 treatment of hypercalcemia or spinal cord compression with corticosteroids or
 radiation therapy, respectively, does not disqualify the subject (the dose of
 corticosteroids should not exceed the equivalent of 160 mg of dexamethasone in 2-week
 period).

 -  Radiation therapy within 2 weeks before randomization. Enrollment of patients who
 require concurrent radiotherapy (which must be localized in its field size) should be
 deferred until the radiotherapy is completed and 2 weeks have elapsed since the last
 date of therapy.

 -  Major surgery within 30 days before randomization (Kyphoplasty is not considered major
 surgery)

 -  History of allergy to any of the study medications, their analogues, or excipients in
 the various formulations

 -  ≥Grade 2 peripheral neuropathy on clinical examination within 21 days before
 enrollment.

 -  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 by
 the 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 related
 to myeloma and there has been demonstrated a response to hydration, the subject
 may be enrolled.

 -  Myocardial infarction within 6 months prior to enrollment or New York Hospital
 Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled
 ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or
 significant conduction system abnormalities in the opinion of the investigator. Prior
 to study entry, any abnormality on electrocardiogram at screening must be determined
 and documented by the investigator as not medically relevant.

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

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

 -  Female who is pregnant or breastfeeding. Female participants of childbearing potential
 must have a negative pregnancy test with a sensitivity of at least 50 mIU/mL during
 Screening.

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