Inclusion Criteria:

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

2. Males and females ≥ 18 years of age

3. Multiple Myeloma

4. Documented relapsed or progressive disease (PD) after receiving at least two prior
treatment regimens (induction therapy with autologous stem cell transplant and
maintenance is considered a single regimen), and must have achieved a minimal
response or better to at least one of the regimens

5. Current measurable disease, as indicated by one or more of the following:

- Serum M-protein ≥ 0.5 g/dL

- Urine M-protein ≥ 200 mg/24 hours

- Serum Free Light Chain assay : Involved FLC level ≥ 10 mg/dL provided serum FLC
ratio is abnormal

6. Life expectancy of more than three months

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

8. Adequate hepatic function, with bilirubin < 2 times the upper limit of normal (ULN)
and alanine aminotransferase (ALT) < 3 times ULN

9. Total white blood cell (WBC) count ≥ 2,000/mm3

10. Absolute neutrophil count (ANC) ≥ 1,000/mm3

11. Hemoglobin ≥ 7 gm/dL

- Subjects may receive red blood cell (RBC) transfusions or supportive care with
erythropoietin or darbepoetin in accordance with institutional guidelines

12. Platelet count ≥ 30,000/ mm3

13. 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

14. Male subjects must use an effective barrier method of contraception during study and
for three months following the last dose if sexually active with a female of
child-bearing potential

Exclusion Criteria:

1. Glucocorticoid therapy in a dose equivalent to prednisone ≥ 20 mg/day within 14 days
prior to first dose of study drug

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

3. Plasma cell leukemia

4. Chemotherapy with approved or investigative anticancer therapeutics, including
steroid therapy dose as defined above, within 14 days prior to first dose of study
drug or antibody therapy within 6 weeks prior to first dose of study drug

5. Radiation therapy or immunotherapy within 3 weeks prior to first dose; localized
radiation therapy within 1 week prior to first dose

6. Participation in an investigational therapeutic study within 14 days prior to first
dose of study drug

7. Prior carfilzomib treatment

8. Pregnant or lactating females

9. Major surgery within 3 weeks prior to first dose of study drug

10. Congestive heart failure (New York Heart Association Class III to IV), symptomatic
ischemia, conduction abnormalities or myocardial infarction in the three months prior
to first dose of study drug

11. Uncontrolled hypertension

12. Recent history of acute active infection requiring systemic antibiotics, antivirals,
or antifungals within two weeks prior to first dose of study drug

13. Known or suspected HIV infection, known HIV seropositivity

14. Active hepatitis A, B, or C infection

15. Other malignancy within the past 3 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 7 with stable prostate specific antigen (PSA) levels

16. Any clinically significant medical or psychiatric disease or condition that, in the
Investigator's opinion, may interfere with protocol adherence or a subject's ability
to give informed consent

17. Significant neuropathy (Grade 3, Grade 4, or Grade 2 with pain) at the time of the
first dose and/or within 14 days prior to enrollment

18. Subjects in whom the required program of oral hydration and intravenous fluid
hydration is contraindicated, e.g., due to preexisting pulmonary or cardiac
impairment

19. Subjects with pleural effusions requiring routine thoracentesis or ascites requiring
routine paracentesis

20. Subjects with a known contraindication to receiving dexamethasone or allopurinol

21. Receipt of granulocyte- and granulocyte/ macrophage- colony stimulating factor (G-CSF
and GM-CSF) within 1 week prior to first dose of study drug

22. Receipt of pegylated G-CSF within 2 weeks prior to first dose of study drug

23. RBC and platelet transfusions within 7 days prior to first dose of study drug

24. Subjects with known or suspected cardiac amyloidosis

25. Subjects with myelodysplastic syndrome

26. Subjects undergoing peritoneal dialysis