The purpose of this study is to determine safety and the maximum tolerated dose (MTD) of GRN163L and Velcade with and without Decadron when administered to patients with refractory or relapsed multiple myeloma.

GRN163L is a telomerase template antagonist with in vitro and in vivo activity in a variety of tumor model systems. Telomerase is an enzyme that is active primarily in tumor cells and is crucial for the indefinite growth of tumor cells. Inhibition of telomerase may result in antineoplastic effects.

Inclusion Criteria:

• Confirmed diagnosis of multiple myeloma (either secretory or nonsecretory disease)
• Relapsed or refractory disease
• ECOG performance status 0-2
• Adequate hepatic/renal function and platelet count
• If previously treated with an anthracycline, anthracenedione, or trastuzumab, must have left ventricular ejection fraction > 50%
• Fully recovered from any previous cancer treatments and/or major surgery

Exclusion Criteria:

• Prior allogeneic bone marrow transplant, including syngeneic transplant
• Bone marrow transplant within 12 weeks prior to study
• Known intracranial disease or epidural disease
• Inability to tolerate Velcade
• Inability to tolerate Decadron
• Prior malignancy (within the last 3 years)
• Clinically significant cardiovascular disease or condition
• Active or chronically recurrent bleeding (eg, active peptic ulcer disease
• Prolongation of PT or aPTT > the ULN or fibrinogen < the LLN
• Clinically relevant active infection
• Serious co-morbid medical conditions, including cirrhosis and chronic obstructive or chronic restrictive pulmonary disease
• Any other cancer therapy within 4 weeks prior to study, with nitrosourea within 6 weeks prior to study
• Investigational therapy within 4 weeks prior to study
• Anti-platelet therapy within 2 weeks prior to study, other than low dose aspirin prophylaxis therapy and low dose heparin administration for management of IV access devices
• Radiation therapy within 4 weeks prior to study
• Major surgery within 4 weeks prior to study
• Active autoimmune disease requiring immunosuppressive therapy
• Known positive serology for HIV