|Inclusion Criteria:||1) The subject has MM confirmed by all three of the following International Myeloma Working Group (IMWG) criteria except as noted: Clonal bone marrow plasma cells > 10%; or documented plasmacytoma if clonal bone marrow cells < 10%; Monoclonal paraprotein (M protein) in either serum or urine (except in subjects with non-secretory myeloma); Evidence of end-organ damage that can be attributed to the underlying plasma cell proliferative disorder (to include one of the following): Hypercalcemia (corrected calcium > 2.75 mmol/L or 11.5 mg/dL); OR (continued under Inclusion #2)|
2) (Continuation of Inclusion #1) Renal insufficiency attributable to myeloma; OR Anemia; normochromic, normocytic with a hemoglobin value > 2 g/dL below the lower limit of normal or a hemoglobin < 10 g/dL; OR Bone lytic lesions, severe osteopenia or pathologic fractures.
3) The subject has received one and no more than three prior regimens for MM to which they did not respond (failed) or from which they have relapsed. A planned treatment of induction regimens followed by autologous stem cell transplant (ASCT) followed by maintenance therapy is considered one regimen. Failure of therapy is defined as either: Failure to achieve at least a PR (IMWG criteria) after a period of therapy of adequate duration, in the Investigator's opinion, to see such a response; OR Discontinuation of therapy due to toxicity, regardless of response status; (continued under Inclusion #4)
4) (Continuation of Inclusion #3) Development of PD after initial response (complete or partial) to a therapy but PD occurred while continuing to receive that therapy. Relapse is defined as PD (IMWG criteria) after a response to treatment and discontinuation of that treatment.
5) The subject must have disease that can be evaluated by serum or urine levels of M protein or serum free light chains (FLC) if no measurable M protein, as follows: Serum M protein >/= 1 gm/dL; or Urine M protein >/= 200 mg/24hr; or Serum FLC: Involved FLC level >/= 10 mg/dL with abnormal k/alpha FLC ration (normal ration =0.26 - 1.65) in patients without measurable M protein in serum or urine.
6) The subject has an Eastern Cooperative Oncology Group (ECOG) performance status score of </= 2 at study entry.
7) The subject is >/= 18 years of age.
8) The subject has a life expectancy >/= 3 months.
9) The subject has completed any prior chemotherapy (including dexamethasone > 2.5 mg/day) investigational agents, and/or prior radiotherapy at least four weeks prior to entry (nitrosoureas at least six weeks), and monoclonal antibody therapy at least six weeks prior to the first dose of study medication.
10) If a subject has received prior treatment with thalidomide, lenalidomide or high dose steroids, these medications must be stopped at least four weeks prior to the first dose of study medication.
11) If the subject has received prior bortezomib (or another proteasome inhibitor) alone or in combination, then they must not have progressed while receiving bortezomib (or another proteasome inhibitor) and a minimum of 60 days must have elapsed since their last treatment with bortezomib (or another proteasome inhibitor).
12) The subject has resolution of all clinically significant toxic effects of prior cancer therapy to Grade </= 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI-CTCAE v 4.0), excluding the Inclusion Criteria required in #13,14, and 15 below.
13) The subject has adequate hematological function: absolute neutrophil count (ANC) >/= 1,000 cells/microL (or >/= 1 x 10^9/L); hemoglobin >/= 9.0 g/dL (may be transfused to meet this requirement); and platelets >/= 50,000 cells/microL (or >/= 50 x 10^9/L).
14) The subject has adequate hepatic function: bilirubin < 1.5 times the upper limit of normal ([ULN], excluding unconjugated hyperbilirubinemia in Gilbert's syndrome), aspartate transaminase (AST), and alanine transaminase (ALT) each < 2.5 x ULN
15) The subject has serum creatinine </= 177 micromol/L (2.0 mg/dL) or a calculated creatinine clearance > 30 mL/min/1.73 m^2 for subjects with creatinine levels > 177 micromol/L.
16) The subject has provided signed informed consent. Written informed consent must be obtained prior to performing any study-related procedures.
17) For women of child-bearing potential (WOCBP) a negative pregnancy test must be obtained prior to study entry. WOCBP and male subjects with female partners of child-bearing potential must, during study drug treatment, and for 3 months after last bortezomib administration, agree to use a highly effective method of birth control (i.e., condom or diaphragm + spermicide, some intrauterine devices, hormonal contraceptive, true sexual abstinence or male vasectomy). (Continued under Inclusion # 18).
18) (Conintuation of Inclusion # 17) Since it is not known whether the treatment reduces the effectiveness of hormonal contraception a second non-hormonal method should always be added to a hormonal method. Women are considered not to be of child-bearing potential if they have been surgically sterilized (hysterectomy, tubal occlusion or bilateral salpingectomy) or are postmenopausal (complete absence of menses for two consecutive years and a serum FSH level of >/= 30 IU/L in the absence of hormone replacement therapy [HRT]).
19) The subject has completed all assessments for determining eligibility within 21 days preceding the first dose of KW-2478/bortezomib.