| Exclusion Criteria: | 1) Multiple myeloma IgM
2) Subjects previously treated with any proteasome inhibitor (under Amendment 2)
3) Subject must not be primary refractory to standard first-line therapy
4) Subjects with non-secretory multiple myeloma, defined as <1 g/dL M-protein in serum, and <200 mg/24 hr M-protein in urine
5) Glucocorticoid therapy (prednisone >10 mg/day orally or equivalent) within the last three weeks.
6) POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
7) Plasma cell leukemia.
8) Chemotherapy with approved or investigative anticancer therapeutics including steroid therapy within the three weeks prior to first dose.
9) Radiation therapy or immunotherapy in the previous four weeks; localized radiation therapy within 1 week prior to first dose.
10) Participation in an investigational therapeutic study within three weeks or within five drug half-lives (t1/2) prior to first dose,whichever time is greater.
11) Prior treatment with carfilzomib.
12) Major surgery within three weeks before Day 1.
13) Congestive heart failure (New York Heart Association class III toIV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction in the previous six months.
14) Acute active infection requiring systemic antibiotics, antivirals or antifungals within 2 weeks prior to first dose.
15) Known or suspected HIV infection or subjects who are HIV seropositive
16) Active hepatitis A, B, or C infection
17) Non-hematologic malignancy within the past three years except a) adequately treated basal cell or squamous cell skin cancer, b) carcinoma in situ of the cervix, or c) prostate cancer <Gleason Grade 6 with stable PSA.
18) Subjects with treatment related myelodysplastic syndrome.
19) Significant neuropathy (Grade 3, 4 or Grade 2 with pain) at the time of study initiation.
20) Subjects with known contraindication to receiving allopurinol
21) Subjects in whom the required program of oral and intravenous fluid hydration is contraindicated, e.g., due to pre-existing pulmonary, cardiac, or renal impairment
22) Any clinically significant medical disease or condition that, in the investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent
23) Subjects with known or suspected amyloidosis
24) Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis
25) Female subjects who are pregnant or lactating.
26) Serious psychiatric or medical conditions that could interfere with treatment. |