Inclusion Criteria:

1. Symptomatic multiple myeloma

2. Measurable disease, as defined by one or more of the following (assessed within 21
days prior to randomization):

- Serum M-protein ≥ 0.5 g/dL

- Urine Bence-Jones 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)

3. Prior treatment with at least one, but no more than three, regimens for multiple
myeloma

4. Documented relapse or progressive disease on or after any regimen

5. Achieved a response to at least one prior regimen

6. Age ≥ 18 years

7. Life expectancy ≥ 3 months

8. Eastern Cooperative Oncology Group performance status 0-2

9. Adequate hepatic function, with serum ALT ≤ 3.5 times the upper limit of normal and
serum direct bilirubin ≤ 2 mg/dL (34 µmol/L) within 21 days prior to randomization

10. Absolute neutrophil count ≥ 1.0 × 10^9/L within 21 days prior to randomization

11. Hemoglobin ≥ 8 g/dL (80 g/L) within 21 days prior to randomization

12. Platelet count ≥ 50 × 10^9/L (≥ 30 × 10^9/L if myeloma involvement in the bone marrow
is > 50%) within 21 days prior to randomization

13. Creatinine clearance (CrCl) ≥ 50 mL/minute within 21 days prior to randomization

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

15. Females of childbearing potential must agree to ongoing pregnancy testing and to
practice contraception

16. Male subjects must agree to practice contraception

Exclusion Criteria:

1. If previously treated with bortezomib (alone or in combination), progression during
treatment

2. If previously treated with a lenalidomide and dexamethasone (len/dex) combination:

- Progression during the first 3 months of initiating treatment

- Any progression during treatment if the len/dex combination was the subject's
most recent line of therapy

3. Discontinuation of previous lenalidomide or dexamethasone due to intolerance;
subjects intolerant to bortezomib are not excluded

4. Prior carfilzomib treatment

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

6. Waldenström's macroglobulinemia or IgM myeloma

7. Plasma cell leukemia (> 2.0 × 10^9/L circulating plasma cells by standard
differential)

8. Chemotherapy or investigational agent within 3 weeks prior to randomization or
antibody therapy within 6 weeks prior to randomization

9. Radiotherapy to multiple sites or immunotherapy/antibody therapy within 28 days prior
to randomization; localized radiotherapy to a single site within 7 days prior to
randomization

10. Corticosteroid therapy at a dose equivalent to dexamethasone > 4 mg/day within 21
days prior to randomization

11. Pregnant or lactating females

12. Major surgery within 21 days prior to randomization

13. Acute active infection requiring treatment (systemic antibiotics, antivirals, or
antifungals) within 14 days prior to randomization

14. Known human immunodeficiency virus infection

15. Active hepatitis B or C infection

16. Myocardial infarction within 4 months prior to randomization, NYHA Class III or IV
heart failure, uncontrolled angina, history of severe coronary artery disease, severe
uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic
evidence of acute ischemia or Grade 3 conduction system abnormalities unless subject
has a pacemaker

17. Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to
randomization

18. Other malignancy, including MDS, within the past 3 years with the exception of a)
adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid
cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason
Grade 6 or less with stable prostate-specific antigen levels; or d) cancer considered
cured by surgical resection or unlikely to impact survival during the duration of the
study, such as localized transitional cell carcinoma of the bladder or benign tumors
of the adrenal or pancreas

19. Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 14 days prior to
randomization

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

21. Contraindication to any of the required concomitant drugs or supportive treatments,
including hypersensitivity to all anticoagulation and antiplatelet options, antiviral
drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment

22. Ongoing graft-vs-host disease

23. Subjects with pleural effusions requiring thoracentesis or ascites requiring
paracentesis within 14 days prior to randomization

24. Any other 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