Inclusion Criteria:

• Male or female and at least 18 years-of-age
• Confirmed diagnosis of multiple myeloma with evaluable disease parameters
• Progression of disease after an initial response (complete, partial, or minimal) to at least 1 line of therapy
• Life expectancy of at least 3 months
• At randomization specific hematologic and biochemical values
• Acceptable cardiovascular function
• Recovered from the acute toxicity of any prior treatment
• Female subjects, or the female partners of male subjects, practicing an effective method of birth control
• Negative serum or urine b-hCG pregnancy test at screening for subjects of child-bearing potential
• Able to respond to health outcomes questionnaire
• Subjects (or their legally acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study

Exclusion Criteria:

• History of treatment with VELCADE
• Progressive disease while receiving an anthracycline-containing regimen
• No change (NC) in disease status during initial therapy
• Non-secretory disease
• Prior treatment with doxorubicin or other anthracycline at cumulative doses greater than 240 mg/m2
• Myocardial infarct within 6 months before enrollment
• Treatment with nitrosoureas within 42 days before randomization
• Treatment with chemotherapy (other than nitrosoureas), clarithromycin, or immunotherapy (e.g.—interferon) within 21 days before randomization
• Treatment with antibody therapy within 60 days before randomization
• Treatment with plasmapheresis within 30 days before randomization
• Major surgery within 30 days before randomization
• Radiation therapy within 30 days before randomization
• Allergic reactions to compounds containing boron, mannitol or doxorubicin, or other components of DOXIL/CAELYX or VELCADE
• Treatment for a malignant condition, other than multiple myeloma, within the 5 years prior to enrollment; except for basal cell carcinoma of the skin, non-metastatic squamous cell carcinoma of the skin, or cervical cancer in situ within the past 5 years
• Known to be seropositive for HIV, or active hepatitis A, B, or C infection
• Poorly controlled hypertension, diabetes mellitus or other serious medical or psychiatric conditions that could interfere with adherence to or completion of this study
• Pregnant or breast-feeding
• Use of an investigational drug or medical device within 30 days before randomization