Inclusion Criteria:

1. MM with relapsing or progressive disease at study entry

a. Defined as progressive MM on patient's last treatment regimen

2. Measurable disease, as defined by one or more of the following (assessed within 14
days prior to first dose):

1. Serum M-protein ≥ 0.5 g/dL, or

2. Urine M-protein ≥ 200 mg/24 hours, or

3. Only in patients who do not meet a or b, then use serum free light chain
(SFLC) > 100 mg/L (involved light chain) and an abnormal kappa/lamda ratio

3. Age ≥ 18 years

4. Life expectancy ≥ 6 months

5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

6. Adequate hepatic function within 14 days prior to first dose, with bilirubin < 1.5 ×
the upper limit of normal (ULN), and aspartate aminotransferase (AST) and alanine
aminotransferase (ALT) < 3 × ULN

7. LVEF ≥ 40%. 2-D transthoracic echocardiogram (ECHO) is the preferred method of
evaluation. Multigated Acquisition Scan (MUGA) is acceptable if ECHO is not
available.

8. Absolute neutrophil count (ANC) ≥ 1000/mm3 within 14 days prior to first dose.
Screening ANC is to be independent of granulocyte colony stimulating factor support
for ≥ 1 week and pegylated granulocyte colony stimulating factor for ≥ 2 weeks.

9. Hemoglobin ≥ 8.0 g/dL within 14 days prior to enrollment. Use of erythropoietic
stimulating factors and red blood cell (RBC) transfusions per institutional
guidelines is allowed.

10. Platelet count ≥ 75,000/mm3 (≥ 50,000/mm^3 if myeloma involvement in the bone marrow
is > 50%) within 14 days prior to first dose. Patients must not have received
platelet transfusions for at least 7 days prior to obtaining the screening platelet
count

11. Calculated or measured creatinine clearance (CrCl) of ≥ 15 mL/min within 14 days
prior to first dose. Calculation are based on a standard formula, such as the
Cockcroft and Gault: [(140 - Age) x Mass (kg) / (72 x Creatinine mg/dL)]; multiply
result by 0.85 if female

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

13. Female patients of childbearing potential (FCBP) must have a negative serum pregnancy
test within 14 days prior to first dose and agree to use an effective method of
contraception during and for 3 months following last dose of drug (more frequent
pregnancy tests may be conducted if required per local regulations). Postmenopausal
females (> 45 years old and without menses for > 1 year) and surgically sterilized
females are exempt from a pregnancy test

14. Male patients must agree to use an effective barrier method of contraception during
study and for 3 months following the last dose if sexually active with a FCBP

Exclusion Criteria:

1. Multiple myeloma of IgM subtype

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

3. Plasma cell leukemia (> 2.0 × 109/L circulating plasma cells by standard
differential)

4. Waldenström's macroglobulinemia

5. Amyloidosis

6. Glucocorticoid therapy (prednisone > 30 mg/day or equivalent) within 7 days prior to
first dose

7. Cytotoxic chemotherapy with approved or investigational anticancer therapeutics
within 28 days prior to first dose

8. Treatment with bortezomib, thalidomide or lenalidomide within 21 days prior to first
dose

9. Focal radiation therapy within 7 days prior to first dose. Radiation therapy to an
extended field involving a significant volume of bone marrow within 21 days prior to
enrollment (i.e., prior radiation must have been to < 30% of the bone marrow)

10. Immunotherapy within 21 days prior to first dose

11. Major surgery within 21 days prior to first dose

12. Active congestive heart failure (New York Heart Association [NYHA] Classes III to
IV), symptomatic ischemia, or conduction abnormalities uncontrolled by conventional
intervention. Myocardial infarction within 6 months prior to first dose.

13. Acute active infection requiring systemic antibiotics, antiviral (except antiviral
therapy directed at HBV), or antifungal agents within 14 days prior to first dose

14. Known human immunodeficiency virus (HIV) seropositivity

15. Known hepatitis B or C virus infection (except for patients with HBV receiving and
responding to HBV antiviral therapy: these patients are allowed)

16. Patients with known cirrhosis

17. Second malignancy within the past 3 years, except:

1. Adequately treated basal cell or squamous cell skin cancer

2. Carcinoma in situ of the cervix

3. Prostate cancer < Gleason score 6 with stable prostate-specific antigen (PSA)
over 12 months

4. Breast carcinoma in situ with full surgical resection

5. Treated medullary or papillary thyroid cancer

6. Patients with myelodysplastic syndrome

18. Significant neuropathy (Grades 3 to 4) within 14 days prior to first dose

19. Peripheral neuropathy with pain ≥ G2 within 14 days prior to first dose

20. Female patients who are pregnant or lactating

21. Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize
carfilzomib)

22. Prior carfilzomib treatment

23. Prior participation in any Onyx-sponsored phase 3 trial

24. Patients with contraindication to dexamethasone

25. Contraindication to any of the required concomitant drugs or supportive treatments,
including hypersensitivity to antiviral drugs, or intolerance to hydration due to
preexisting pulmonary or cardiac impairment

26. Ongoing graft-versus-host disease

27. Patients with pleural effusions requiring thoracentesis or ascites requiring
paracentesis within 14 days prior to enrollment

28. Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to enrollment

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