Inclusion Criteria:

• Males and females with a diagnosis of MM based on bone marrow aspirate and biopsy with ≥10% plasma cells (or biopsy of a tissue with monoclonal plasma cells), M protein level in the serum or urine, and evidence of end organ or tissue impairment (hypercalcemia, renal insufficiency, anemia, or lytic bone lesions), as defined by The International Myeloma Working Group Criteria (2003), at initial diagnosis (before initiation of chemotherapy).
• Measurable disease defined as serum and/or urine M component by electrophoresis
• Refractory to or relapsed after 2 prior treatment regimens (chemotherapy, biologic or hematopoietic stem cell transplantation)
• Concurrent therapy with a bisphosphonate is acceptable
• ECOG performance status of 0 or 1
• Life expectancy ≥3 months
• Adequate liver function
• No other malignancies within 5 years
• Signed informed consent

Exclusion Criteria:

• Nonsecretory myeloma, monoclonal gammopathy of uncertain significance (MGUS), or smoldering myeloma.
• Anticancer therapy including chemotherapeutic, biologic, or investigational agents, including dexamethasone, within 30 days of XL999 treatment
• Hematopoietic stem cell transplantation within the previous 6 weeks
• Radiation to ≥33% of bone marrow within 30 days of XL999 treatment
• Subject has not recovered to grade ≤1 or to within 10% of baseline from adverse events due to investigational or chemotherapeutic drugs that were administered >30 prior to study enrollment
• Uncontrolled and/or intercurrent illness
• Pregnant or breastfeeding females
• Known HIV