A Pilot Study of the Combination of Melphalan, Bortezomib, Thalidomide and Dexamethasone (MEL-VTD)

Inclusion Criteria: * History of histologically documented MM with relapsed or progressive disease after either scheduled tandem or one autologous transplantation. * Patient has measurable disease in which to capture response. * Performance status of 2 as per Zubroid scale, unless PS of 3-4 based solely on bone pain. * Patients must have a platelet count 75,000/μL, and an ANC of at least 1,000/μL. * Patients must have adequate renal function defined as serum creatinine \< 2.5 mg/dL. * 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 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 an IRB-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 2 weeks. * Significant neurotoxicity, defined as grade \> 2 neurotoxicity per NCI Common Toxicity Criteria (See Appendix). * Platelet count \< 75,000/mm3, or ANC \< 1,000/μl. * 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 (NYHA) Class III or Class IV heart failure. * Myocardial infarction within the last 6 months. * Uncontrolled, active infection requiring IV antibiotics. * 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 test at screening, and will be required to use a medically approved contraceptive method. * Breast-feeding women may not participate.