Study of Velcade® and Bone Formation in Patients With Relapsed/Refractory Multiple Myeloma

Inclusion Criteria:

* History of histologically documented MM with relapsed or progressive disease after at least one line of prior therapy.
* Patient has measurable disease in which to capture response, defined as one or more of the following:

  * Serum M-protein level \> 1.0 gm/dl (10.0 g/L) measured by serum protein electrophoresis or immunoglobulin electrophoresis; or
  * Urinary M-protein excretion \> 1000 mg/24 hours; or
  * Bone marrow plasmacytosis of \> 30% by bone marrow aspirate and/or biopsy; or
  * Serum free light chains (by the Freelite test) \> 2 X the upper limit of normal, in the absence of renal failure.
  * Evidence of active disease by radiographic techniques
* Performance status (PS) of \<= 2 as per Southwest Oncology Group scale, unless PS of 3-4 based solely on bone pain.
* Patients must have a platelet count \>= 50,000/mm3, and an absolute neutrophil count of at least 1,000/μl.
* Patients must have adequate renal function defined as creatinine clearance \> 30ml/min.
* Patients must have adequate hepatic function defined as serum transaminases and direct bilirubin \< 2 X the upper limit of normal.
* Pregnant or nursing women may not participate. Women of childbearing potential must have a negative pregnancy test documented within one week of registration. Women of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
* Male or female adults of at least 18 years of age.
* Patients must have signed and Institutional Review Board approved written informed consent form and demonstrate willingness to meet follow-up schedule and study procedure obligations

Exclusion Criteria:

* Chemotherapy or radiotherapy received within the previous 4 weeks.
* Has received previous bortezomib therapy
* Significant neurotoxicity, defined as grade \> 2 neurotoxicity per National Cancer Institute Common Toxicity Criteria.
* Platelet count \< 50,000/mm3, or ANC \< 1,000/μl
* Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome.
* Patient has hypersensitivity to bortezomib, boron, or mannitol
* Clinically significant hepatic dysfunction as noted by bilirubin or AST \>3 times the upper normal limit or clinically significant concurrent hepatitis.
* New York Hospital Association Class III or Class IV heart failure.
* Myocardial infarction within the last 6 months.
* Non-secretory multiple myeloma, unless the patient has measurable lesions on computed tomography, magnetic resonance imaging and/or positron emission tomography.
* Uncontrolled, active infection.
* Patients with a history of treatment for clinically significant ventricular cardiac arrhythmias.
* Poorly controlled hypertension, diabetes mellitus, or other serious or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol.
* Pregnant or potential for pregnancy. Women of childbearing potential will have a pregnancy \[beta-HCG\] test at screening, and will be required to use a medically approved contraceptive method. Pregnancy testing will be performed prior to administration of each cycle of study drug.
* Breast-feeding women may not participate.