Inclusion Criteria:

Disease Related

- Multiple myeloma

- Subjects must have measurable disease, defined as one or more of the following:

- Serum M-protein ≥ 1 g/dL

- Urine M-protein ≥ 200 mg/24 hours

- Subjects must have been responsive (i.e., achieve an MR or better) to standard, first
line therapy

- Relapsed and/or refractory or progressive disease after at least one, but no more
than three, prior therapeutic treatments or regimens for multiple myeloma. Refractory
disease is defined as ≤ 25% response or progression during therapy or within 60 days
after completion of therapy. Induction therapy and stem cell transplant will be
considered as one regimen

Demographic

- Males and females ≥18 years of age

- Life expectancy of more than three months

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2

Laboratory

- Adequate hepatic function, with bilirubin < 2.0 times the upper limit of normal, and
AST and ALT of < 3.0 times the upper limit of normal

- Uric acid, if elevated, must be corrected to within laboratory normal range prior to
dosing

- Total WBC count ≥ 2,000/mm3, absolute neutrophil count > 1,000/mm3, hemoglobin ≥ 8.0
g/dL, and platelet count > 50,000/mm3

- Subjects should be platelet transfusion independent

- Screening ANC should be independent of G-CSF or GM-CSF support for ≥ 1 week and of
pegylated G-CSF for ≥ 2 weeks

- Subjects may receive RBC transfusion or receive supportive care such as
erythropoietin and darbepoetin in accordance with institutional guidelines

- Calculated or measured creatinine clearance of ≥ 30 mL/minute, calculated using the
formula of Cockcroft and Gault [(140 - Age) X Mass (kg) / (72 X Creatinine mg/dL)].
Multiply result by 0.85 if female.

- Serum creatinine ≤ 2 mg/dL

Ethical / Other

- Written informed consent in accordance with federal, local, and institutional
guidelines

- Female subjects of child-bearing potential must have a negative serum pregnancy test
within seven days of the first dose and agree to use dual methods of contraception
during and for 3 months following last dose of drug. Post menopausal females (> 45
years old and without menses for > 1 year) and surgically sterilized females are
exempt from a pregnancy test. Male subjects must use an effective barrier method of
contraception during study and for 3 months following the last dose if sexually
active with a female of child-bearing potential.

- Subjects must be able to receive outpatient treatment and laboratory monitoring at
the institute that administers agent.

Exclusion Criteria:

Disease Related

- Multiple Myeloma IgM

- Subjects previously treated with any proteasome inhibitor (under Amendment 2)

- Subjects must not be primary refractory to standard first-line therapy

- Subjects with non-secretory multiple myeloma, defined as < 1 g/dL M-protein in serum,
< 200 mg/24 hr M-protein in urine

- Subjects with disease measurable only by serum free light chain (SFLC) analysis

- Glucocorticoid therapy (prednisone >10 mg/day orally or equivalent) within the last
three weeks

- POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and
skin changes)

- Plasma cell leukemia

- Chemotherapy with approved or investigative anticancer therapeutics, including
steroid therapy, within the three weeks prior to first dose

- Radiation therapy or immunotherapy in the previous four weeks; localized radiation
therapy within 1 week prior to first dose

- 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

- Prior treatment with carfilzomib

Concurrent Conditions

- Major surgery within three weeks before Day 1

- Congestive heart failure (New York Heart Association class III to IV), symptomatic
ischemia, conduction abnormalities uncontrolled by conventional intervention, or
myocardial infarction in the previous six months

- Acute active infection requiring systemic antibiotics, antivirals or antifungals
within 2 weeks prior to first dose

- Known or suspected HIV infection or subjects who are HIV seropositive

- Active hepatitis A, B, or C infection

- 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

- Subjects with treatment related myelodysplastic syndrome

- Significant neuropathy (Grade 3, 4 or Grade 2 with pain) at the time of study
initiation

- Subjects with known contraindication to receiving allopurinol

- 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

- Subjects with known or suspected amyloidosis Subjects with pleural effusions
requiring thoracentesis or ascites requiring paracentesis

- 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

Ethical / Other

- Female subjects who are pregnant or lactating

- Serious psychiatric or medical conditions that could interfere with treatment