Inclusion Criteria:

1. Histologically documented multiple myeloma

2. Age ≥ 18 years

3. ECOG status 0-2.

4. Life expectancy ≥3 months.

5. Measurable disease, defined as one or more of the following:

- Serum M-protein ≥1 g/dL.

- Urine M-protein ≥200 mg/24 hours.

- For IgA patients whose disease can only be reliably measured by serum
quantitative immunoglobulin (qIgA), ≥750 mg/dl (0.75 g/dl).

6. For oligosecretory or non-secretory MM, either of the following:

- Measurable plasmacytoma >2 cm as determined by clinical examination or
applicable radiographs (ie, magnetic resonance imaging [MRI], computed
tomography [CT]scan).

- Documented abnormal free light chain ratio (NV: 0.26 to 1.65) or a value beyond
the laboratory calculation range.

7. Received and either refractory or relapsed or discontinued due to toxicity to at
least 4 prior lines of therapy as described below:

- an immunomodulatory agent (lenolidamide or thalidomide)

- bortezomib

- an alkylating agent (standard or high dose)

- a corticosteroid

8. Currently has progressive disease.

9. Refractory multiple myeloma defined as meeting one or more of the following:

- Nonresponsive to most recent therapy (eg, stable disease only, or progressive
disease while on treatment).

- Disease progression within 60 days of discontinuation of most recent therapy
(most recent therapy must be within 60 days of Screening).

10. LVEF ≥40% within 30 days before Cycle 1 Day 1. 2-D transthoracic ECHO is the
preferred method of evaluation; MUGA is acceptable if ECHO is not available.

11. Adequate hepatic function, defined as AST (SGOT) and ALT (SGPT) <3 times the upper
limit of normal and serum bilirubin ≤2.5 mg/dl.

12. Absolute neutrophil count ≥1,000 (may be supported by growth factors) and platelet
count ≥40,000 within 14 days before Cycle 1 Day 1 without transfusion.

13. Creatinine clearance (CrCl) ≥15 mL/minute (measured or calculated using the Cockcroft
and Gault Formula) within 14 days before Cycle 1 Day 1. This criterion does not apply
to patients on hemodialysis.

14. Female patients of childbearing potential must have a negative serum pregnancy test
within 7 days before Cycle 1 Day 1 and must agree to use dual contraception methods
for the duration of treatment and for 3 months following the last dose of treatment.
Male patients must use an effective barrier method of contraception if sexually
active with a female of childbearing potential during the treatment period and for 3
months following the last dose of treatment.

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

Exclusion Criteria:

1. Prior treatment with carfilzomib or enrollment in any other Phase 3 carfilzomib
trial.

2. Known human immunodeficiency virus (HIV) seropositivity.

3. Active infection requiring systemic treatment with anti-biotics, anti-virals, or
anti-fungals.

4. Known, active hepatitis A, B, or C viral infection.

5. Concomitant use of approved or investigational anti-cancer therapeutic agents, other
than dexamethasone or palliative radiation therapy. Patients receiving radiation for
pain control are eligible for enrollment in this study. No wash-out period is
required for other anti-myeloma treatments received.

6. Concomitant use of other investigational agents (eg, anti-biotics or anti-emetics).

7. Pregnancy or breastfeeding.

8. History of plasma cell leukemia, defined as >2.0 × 10e9/L circulating plasma cells.

9. History of amyloidosis.

10. Known history of allergy to Captisol®.

11. Active congestive heart failure (New York Heart Association Class 3-4), symptomatic
ischemia, conduction abnormalities uncontrolled by a conventional intervention, or a
myocardial infarction within the past 4 months.

12. Intolerance to hydration due to pre-existing pulmonary, cardiac, or renal impairment.
Patients on hemodialysis should be considered as meeting this criterion for entry.

13. Waldenström macroglobulemia or IgM myeloma.