Bortezomib and Bendamustine to Treat Relapsed/Refractory Myeloma

Inclusion Criteria: 1. Voluntary written informed consent 2. Age 18 years or older 3. 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. 4. Male subject agrees to use an acceptable method for contraception for the duration of the study. 5. Diagnosis of multiple myeloma based on standard criteria as follows: Major Criteria * Plasmacytomas on tissue biopsy * Bone marrow plasmacytosis (\>30% plasma cells) * Monoclonal immunoglobulin spike on serum electrophoresis (IgG \>3.5 g/dL or IgA \>2.0 g/dL) or kappa or lambda light chain excretion \>1 g/day on 24 hour urine protein electrophoresis Minor Criteria * Bone marrow plasmacytosis (10 to 30% plasma cells) * Monoclonal immunoglobulin present but of lesser magnitude than given under major criteria * Lytic bone lesions * Normal IgM \<50 mg/dL, IgA \<100 mg/dL, or IgG \<600 mg/dL * Any of the following sets of criteria will confirm the diagnosis of Multiple Myeloma: * Any two of the major criteria or * 1 major plus 2 minor criteria. 6. Measurable disease, defined as a monoclonal immunoglobulin spike (M-Spike) on serum electrophoresis of ≥1 g/dL and/or urine monoclonal immunoglobulin spike of ≥200 mg/24 hours. Non-secretors must have measurable protein by Freelite or measurable disease by plasmacytoma to be eligible. 7. Patients must have refractory myeloma as defined by a greater than 25% increase in their M-protein. They should have progressed on bortezomib. 8. Karnofsky performance status ≥50 9. Patients treated with local radiotherapy with or without a brief exposure to steroids are eligible. Patients who require radiotherapy should have entry to the protocol deferred until the radiotherapy is completed by at least 4 weeks prior to initiation of study drug. 10. Meets the following pretreatment laboratory criteria at baseline (Day 1 of Cycle 1, before study drug administration) * Absolute neutrophil count ≥1 x 10\^3/uL * Platelet count ≥75 x 10\^3/uL * Hemoglobin ≥8.0 g/dL * Calculated or measured CrCL ≥ 40 mL/min * AST or ALT and total bilirubin \< 3 x ULN 11. Echocardiogram with a \>50% Ejection Fraction Exclusion Criteria: Patients meeting any of the following exclusion criteria are not to be registered on study: 1. POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M-protein) and skin changes) 2. Plasma cell leukemia 3. Receiving steroids daily for other medical conditions, e.g., asthma, systemic lupus erythematosis, rheumatoid arthritis 4. Infection not controlled by antibiotics 5. HIV infection. Patients should provide consent for HIV testing according to the institution's standard practice. 6. Known active hepatitis B or C 7. New York Hospital Association (NYHA) Class III or IV heart failure, Echo or MUGA ejection fraction \< 40% (if known), or EKG evidence of acute ischemic disease 8. Other serious medical or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol 9. Second malignancy requiring treatment in the last 3 years 10. Patient has a calculated or measured creatinine clearance of \<40 mL/min within 14 days before enrollment 11. Patient has \>Grade 2 peripheral neuropathy within 14 days before enrollment 12. Patient has hypersensitivity to bortezomib, boron or mannitol and bendamustine 13. Positive pregnancy test in women of childbearing potential or subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum betaa human chorionic gonadotropin test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women. 14. Patient has received other investigational drugs with 14 days before enrollment 15. Serious medical or psychiatric illness likely to interfere with participation in this clinical study. 16. Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.