A Study to Evaluate Two Different Regimens of VELCADE in Combination With Dexamethasone, Thalidomide and Cyclophosphamide (VDT vs VDTC) in Newly Diagnosed Multiple Myeloma

Inclusion Criteria:

* Male or female between ≥18 and ≤70 years
* Patient is a candidate for HDT combined with an autologous SCT
* Karnofsky Performance Status score of ≥60%
* Multiple myeloma diagnosed according to the following standard criteria AND requiring systemic therapy:
* Presence of M-component in serum and/or urine, plus clonal plasma cells in the bone marrow and/or a documented clonal plasmacytoma
* PLUS 1 or more of the following:

  1. Calcium elevation (\>11.5 mg/dL or \>2.65 mmol/L)
  2. Renal insufficiency (creatinine \>2 mg/dL or \>177 umol/L)
  3. Anemia (hemoglobin \<10 g/dL \[\<12.5 mmol/L\] or at least 2 mg/dL \[1.25 mmol/L\] below normal)
  4. Bone disease (lytic lesions or osteopenia)
* AND fulfill criteria for measurable disease, as defined by at least 1 of the following 3 measurements:

  1. Serum M-protein ≥1 g/dL (≥10 g/L)
  2. Urine M-protein ≥200 mg/24 h
  3. Serum free light chain (FLC) assay: Involved FLC level ≥10 mg/dL (≥100 mg/L) provided serum FLC ratio is abnormal
* Women of childbearing potential must agree to use 2 methods of contraception.
* Males must agree to use barrier contraception.
* Subjects (or their legally acceptable representatives) must have signed an informed consent document.
* To participate in the optional pharmacogenomic component of this study, subjects (or their legally acceptable representative) must have signed the informed consent form. Refusal to consent for this component does not exclude a subject from participation in the clinical study.

Exclusion Criteria:

* Diagnosis of smoldering OR non-secretory multiple myeloma or monoclonal gammopathy of undetermined significance (MGUS).
* Diagnosis of Waldenström's disease or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions.
* Prior or current systemic therapy for multiple myeloma including steroids.
* Radiation therapy and/or plasmapheresis within 15 days before randomization.
* History of allergic reaction attributable to compounds being given (VELCADE, thalidomide, dexamethasone, and/or cyclophosphamide) or compounds containing boron or mannitol.
* Peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0.
* Uncontrolled or severe cardiovascular disease
* Concurrent medical condition or disease (e.g., active systemic infection, uncontrolled diabetes) that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study.
* Use of any investigational drugs within 30 days before randomization
* Pregnant or lactating women: A serum β-hCG pregnancy test must be performed at the Screening visit for female subjects of childbearing potential.
* Employees of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center, as well as family members of the employees or the investigator.