Inclusion Criteria:

• Voluntary written informed consent
• Female subject is either post-menopausal/surgically sterilized or willing to use an acceptable method of birth control for the duration of the study.
• Male subject agrees to use an acceptable method for contraception for the duration of the study.

• Diagnosis of stage II or III multiple myeloma and have relapsed after at least one prior therapies confirmed by the presence of:

  1. A new lytic lesion
  2. A 25% increase in urine or serum monoclonal protein
• Patient can have received PS-341 (Velcade) previously and does not require a previous response.

• Patients must have measurable disease. One or more of the following must be present to qualify for this study:

  1. Serum M-component greater than or equal to 1.0 gm/dl (10.0 g/L) by serum protein electrophoresis
  2. Urine M-protein excretion > 200 mg/24 (0.2 g/24h) hours, by urine protein electrophoresis
  3. Abnormal serum free light chain ratio with elevated Kappa or Lambda light chains in serum
• Baseline measurements must be done within 21 days of study entry.
• Karnofsky Performance Status Scale > 60.
• Greater than or equal to 18 years of age.
• Expected survival of greater than 8 weeks.
• Swallow intact study medication tablets.
• Can follow directions or has a caregiver who will be responsible for administering study medication.

Exclusion Criteria:

• Previously treated with R115777 (Zarnestra).
• Undergone an allogeneic bone marrow transplant.
• A platelet count of <100,000 x 10 to the 9 power/L within 14 days before enrollment.
• Absolute neutrophil count of <1.0 x 10 to the 9 power/L within 14 days before enrollment.
• Measured creatinine > 1.5 X the upper limits of normal within 14 days before enrollment.
• Greater than or equal to Grade 2 peripheral neuropathy within 14 days before enrollment.
• Hypersensitivity to bortezomib, boron, mannitol or imidazole compounds
• Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening.
• Received other investigational drugs within 14 days of enrollment or immunotherapy within 30 days of enrollment.
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
• Ongoing radiation therapy or radiation therapy within 14 days prior to first treatment.
• Cytotoxic chemotherapy within 30 days prior to first treatment.
• Therapy with high-dose corticosteroids within 14 days prior to first treatment.

• Presence of any of the following excludes a patient from entering the study until such condition is resolved (determined within 14 days prior to the first treatment):

  1. Elevated total bilirubin > 2mg/dl, or direct bilirubin > 2 times the ULN.
  2. Serum glutamic oxaloacetic transaminase (AST, formerly SGOT) or serum glutamic pyruvic transaminase (ALT, formerly SGPT) > 2 times the ULN
  3. Serum calcium > 12 mg/dL.
  4. Concurrent serious infection.
  5. Life-threatening illness (unrelated to tumor).
• History of any other ACTIVE and INVASIVE cancer other than the present condition (except non-melanoma skin cancer), unless in complete remission and off of all therapy for that disease for a minimum of 3 years.

• Prohibited/allowable medications or precautions:

  1. Enzyme-inducing anti-epileptic medications (e.g. phenytoin, phenobarbital, cambamazepine) are not allowed.
  2. Non-enzyme anti-epileptic medications will be allowed.