Inclusion Criteria:

• Signed informed consent obtained prior to any study-specific procedures and treatment.
• Previously diagnosed with MM requiring treatment based on IMWG diagnostic criteria.
• Patients with relapsed or refractory MM (Appendix 2) who have exhausted available therapies for their disease.
• Evaluable MM with at least one of the following:
  • serum monoclonal component ≥ 0.5 g/dL; or
  • Bence-Jones (BJ) proteinuria ≥ 200 mg/24h; or
  • measurable plasmacytoma (not previously irradiated); or
  • involved serum free light chain ≥ 10 mg/dL, with an abnormal free light chain ratio.
• Age ≥ 18 years.
• ECOG Performance Status (PS) 0-2.
• Life expectancy > 3 months.
• At least 2 weeks (or 5 half-lives, whichever is longer) wash-out since the end of previously administered experimental therapy (6 weeks if previous nitrosourea containing regimen) or 2 weeks for standard-of-care regimens. Concurrent corticosteroids are allowed provided they are administered at an equivalent prednisone dose of ≤ 10 mg/day, as premedication for blood products only. Additionally, patients who are receiving steroids for adrenal replacement prior to enrollment may continue to receive the same dose of steroids on study.
• Recovery from non-hematologic toxic effects of prior therapy to grade ≤ 1 (except alopecia) by NCI CTCAE Version 4.03.
• Adequate bone marrow (BM), renal, hepatic and metabolic function, defined by:
  • Absolute neutrophil count (ANC) ≥ 1.0 x 109/L (if G-CSF or GM-CSF has been administered within 1 week of screening, must reassess ANC after 1-week washout to confirm no dependence on growth factors);
  • Platelet count ≥ 50 x 109/L (if transfusion has been administered within 1 week of screening, must reassess platelet count after 1-week washout to confirm no transfusion dependence);
  • Hemoglobin ≥ 8.0 g/dL (patients may receive red blood cells (RBC) and/or erythropoietin (EPO) in accordance with institutional guidelines);
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x upper limit of normal (ULN);
  • Total bilirubin ≤ 1.5 x ULN or direct bilirubin ≤ 1.5 x ULN when total bilirubin is > 1.5 x ULN;
  • Calculated creatinine clearance (CrCl) ≥ 30 mL/min (Cockroft & Gault formula or MDRD formula for patients aged ≥ 65 years).
• Women of childbearing potential must have a negative serum pregnancy test before study entry and must be non-lactating; and
• Both women (of childbearing potential) and men must agree to use a medically acceptable method of contraception throughout the treatment period and for 6 months after discontinuing study treatment.

Exclusion Criteria:

• Any of the following concomitant diseases/conditions:
  • History or presence within the last 12 months of myocardial infarction, clinically relevant valvular heart disease, or congestive heart failure within the last 12 months;
  • Unstable cardiac dysrhythmias or persistent prolongation of the corrected QT interval (QTc) (Fridericia) to >500 msec for males or >480 msec for females, based on ECG at screening (patients with stable atrial fibrillation on treatment are allowed provided they do not meet any other cardiac or prohibited drug exclusion criterion);
  • Presence of current angina;
  • Active uncontrolled infection;
  • Morphological or cytological features of myelodysplasia and/or post-chemotherapy aplasia on BM assessment;
  • Myopathy > grade 2 or any clinical situation that causes significant and persistent elevation of CPK (>2.5 x ULN in two different determinations performed one week apart);
  • Peripheral neuropathy > grade 1;
  • POEMS syndrome or active plasma cell leukemia;
  • Chronic graft versus host disease (GVHD) or on immunosuppressive therapy for the control of GVHD;
  • History or presence within the last 3 months of Deep Vein Thrombosis (DVT) or a pulmonary embolism (PE);
  • Uncontrolled leptomeningeal disease;
  • Uncontrolled disease-related metabolic disorder (e.g., hypercalcemia).
  • Acute or chronic infections requiring systemic therapy, including, among others:
    • active infection requiring systemic therapy;
    • history of testing positive to human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome;
    • hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test is positive);
    • active tuberculosis (history of exposure or history of positive TB test with presence of clinical symptoms, physical or radiographic finding).
  • Limitation of the patient’s ability to comply with treatment or follow-up requirements; and
  • Any other major illness that, in the Investigator’s judgment, may substantially increase the risk associated with the patient’s participation in this study.
• History of prior malignancy other than those previously treated with a curative intent more than 5 years ago and without relapse (any tumor) or basal cell skin cancer, in situ cervical cancer, superficial bladder cancer, or high grade intestinal polyps treated adequately, regardless of the disease-free interval.
• History of gastrointestinal bleeding episode occurring within the prior 6 months.
• Prior irradiation to > 30% of BM reserves (including total body irradiation), regardless of the washout period.
• High dose chemotherapy followed by autologous stem cell transplantation within 90 days prior to initiating study treatment.
• Bisphosphonate treatment within 7 days prior to initiating study treatment (while on study, bisphosphonates can be administered only once a month, between Days 18 to 21 of the 28-day treatment cycle).
• Women who are pregnant or breast feeding.
• Known hypersensitivity to any involved study drug or any of its formulation components.

Any waiver of these exclusion criteria should be exceptional and justified and must be approved by the Investigator and the Sponsor on a case-by-case basis prior to enrolling the patient. This must be documented by both the Investigator and Sponsor.