Study Combining Bortezomib With High Dose Melphalan to Treat Multiple Myeloma

Inclusion Criteria:

A confirmed diagnosis of multiple myeloma

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
Age:18yrs-76yrs at time of melphalan administration
Gender: There is no gender restriction

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
Recovery from complications of salvage therapy, if administered -

Exclusion Criteria:

Diagnosis other than multiple myeloma
Chemotherapy or radiotherapy within 28 days of initiating treatment in this study
Prior dose-intense therapy within 56 days of initiating treatment in this study
Uncontrolled bacterial,viral,fungal or parasitic infections
Uncontrolled CNS metastases
Known amyloid deposition in heart

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
Karnofsky score<70% unless a result of bone disease directly caused by myeloma
Life expectancy limited by another co-morbid illness
History of another malignancy in remission <2yrs (other than basal cell carcinoma)
Pregnant (women)or unwilling to use acceptable birth control methods (men or women) for twelve months after treatment
Documented hypersensitivity to melphalan or bortezomib or any components of the formulation
Patients unable or unwilling to provide consent