Study Combining Bortezomib With High Dose Melphalan to Treat Multiple Myeloma

Inclusion Criteria:

1. A confirmed diagnosis of multiple myeloma
2. Show progression of disease after a previous cycle of dose-intense melphalan, or less than 25% decrease in paraprotein measured at 8 weeks after a prior cycle of dose-intense melphalan

   * May have received intervening therapies for disease progression after dose-intense melphalan and enrollment in this protocol
3. Age:18yrs-76yrs at time of melphalan administration
4. Gender: There is no gender restriction
5. Availability of \>2x10\^6 autologous peripheral blood CD34+ cells/kg or a syngeneic donor meeting eligibility criteria for syngeneic donation

   * Syngeneic transplantation is preferred
   * For patients enrolled in the phase I part of this study, \>1x10\^6 autologous or syngeneic peripheral blood CD34+ cells/kg remaining in storage as "backup" in case of engraftment failure
6. Recovery from complications of salvage therapy, if administered -

Exclusion Criteria:

1. Diagnosis other than multiple myeloma
2. Chemotherapy or radiotherapy within 28 days of initiating treatment in this study
3. Prior dose-intense therapy within 56 days of initiating treatment in this study
4. Uncontrolled bacterial,viral,fungal or parasitic infections
5. Uncontrolled CNS metastases
6. Known amyloid deposition in heart
7. Organ dysfunction

   * LVEF\<40% or cardiac failure not responsive to therapy
   * FVC,FEV1,or DLCO\<50% of predicted and/or receiving supplementary continuous oxygen
   * Evidence of hepatic synthetic dysfunction, or total bilirubin\>2x or AST\>3x ULN
   * Measured creatinine clearance \<20ml/min
   * Sensory peripheral neuropathy grade 4
8. Karnofsky score\<70% unless a result of bone disease directly caused by myeloma
9. Life expectancy limited by another co-morbid illness
10. History of another malignancy in remission \<2yrs (other than basal cell carcinoma)
11. Pregnant (women)or unwilling to use acceptable birth control methods (men or women) for twelve months after treatment
12. Documented hypersensitivity to melphalan or bortezomib or any components of the formulation
13. Patients unable or unwilling to provide consent