Inclusion criteria:

• Age ≥ 18 years
• Life expectancy > three months
• Diagnosed with multiple myeloma, based on standard criteria
• Measurable disease, defined as a monoclonal immunoglobulin spike on serum electrophoresis of ≥ 1 gm/dL and /or urine monoclonal immunoglobulin spike of ≥ 200 mg/24-hour
• Relapsed following a response to any conventional MM therapy (including autologous transplantation), and refractory to their most recent MM therapy (including immunotherapy, radiation therapy, or other investigational agents)
• Karnofsky performance status ≥ 60
• No electrocardiographic evidence of acute ischemia or new conduction system abnormalities
• No history of myocardial infarction within last 6 months
• Serum concentrations of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3X upper limit of normal (ULN)
• Total serum bilirubin ≤ 2X ULN
• Calculated or measured creatinine clearance >30 mL/min
• Platelet count ≥ 30 x 10(9)/L
• Hemoglobin concentration ≥ 8 g/dL
• White blood cell count ≥ 2.0 x 10(9)/L
• All baseline assessments for determination of eligibility performed within 35 days prior to first administration of study drug
• Women of childbearing potential (WCBP) must have a negative pregnancy test prior to receiving the first dose of study drug. In addition, sexually active WCBP must agree to use at least two forms of medically accepted birth control, including one barrier method, for the duration of the study
• Men must agree to use an acceptable method for contraception throughout the study
• Fully understand all elements of, and have signed and dated, the written Informed Consent Form (ICF) before initiation of protocol-specified procedures

Exclusion criteria:

• Patients with non-secretory myeloma, plasma cell leukemia, or POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes)
• Major surgery within four weeks of enrollment
• Active uncontrolled infection
• Severe hypercalcemia, i.e., serum calcium ≥ 14 mg/dL (3.5 mmol/L)
• New York Hospital Association (NYHA) Class III or IV heart failure(Appendix 5)
• Receipt of chemotherapy within 21 days before enrollment, with the exception of nitrosoureas (which should be discontinued ≥ 42 days before enrollment)
• Receiving immunotherapy, radiation therapy, or other investigational agents within 30 days before first day of study drug administration
• Receipt of corticosteroids equivalent to more than 10 mg/day of prednisone within two weeks before enrollment
• Known allergies to agents used in bortezomib (e.g., boron or mannitol)
• Poorly controlled hypertension, diabetes mellitus, or other serious medical or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol
• Active hepatitis B infection (HbsAg positive)
• Positive skin or purified protein derivative (PPD) test for tuberculosis
• Known serologic positive for human immunodeficiency virus (HIV)
• Any condition, including laboratory abnormalities, that in the opinion of the investigator places the subject at unacceptable risk if s/he were to participate in the study
• Known allergic reaction to p38 MAPK inhibitors, SCIO-469, or any of its components
• Pregnant or lactating women