Combination High Dose Melphalan and Autologous Peripheral Blood Stem Cell (PBSC) Transplant With Bortezomib for Multiple Myeloma: A Dose and Schedule Finding Study

Inclusion Criteria: * Patients with multiple myeloma who are eligible for an autologous peripheral blood progenitor transplant * Male and female subjects between the age of 18 and 70 years. * Patient has given informed consent prior to any study related procedures with the knowledge that consent can be withdrawn at anytime without prejudice to future medical care * Patient is, in the investigator's opinion, willing and able to comply with the protocol requirements * Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study. * Male subjects agrees to use an acceptable method for contraception for the duration of the study. * Biopsy proven diagnosis of multiple myeloma from bone marrow aspirate and biopsy prior to study initiation * Patient has achieved less than 90% disease reduction from previous treatment prior to transplant (as measured by serum or urine protein electrophoresis) and has more than 5% plasma cells in the bone marrow, or patient has progressed and has more than 5% plasma cells in the bone marrow. * Karnofsky Performance Status score of ≥ 60% * Patient has met the following laboratory requirements prior to Day -4 * Platelet count ≥ 50, 000/mm3 * Absolute Neutrophil Count ≥ 500/mm3 * Hemoglobin ≥ 10 g/dL (transfusion allowed to meet this criterion) * Calculated creatinine clearance ≥ 30mL/min * Toxic effects of previous therapy or surgery resolved to Grade 2 or better Exclusion Criteria: * Unsupportable anemia with \< 10b/dL * Patient has a calculated or measured creatinine clearance of \< 30mL/min within 14 days before enrollment * Patient has ≥ Grade 2 peripheral neuropathy within 14 days before enrollment * Patient has hypersensitivity to bortezomib, boron or mannitol * Patient has had an allergic reaction to melphalan or chlorambucil * Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women. * Patient has received other investigational drugs with 14 days before enrollment * Serious medical or psychiatric illness likely to interfere with participation in this clinical study * Cardiac or pulmonary dysfunction such that patients do not meet institutional pre-transplant evaluation criteria * Known central nervous system involvement or suspicion of involvement with Myeloma * Other active malignancies (with the exception of basal and squamous cell skin cancer) within 5 years of study entry. Patients with treated prostate or cervical cancer in situ who are 2 or more years from therapy and remain free of disease may be entered into the study at the investigator's discretion. * Known to be HIV positive, HIV-1 positive