Inclusion Criteria

Inclusion:

Disease-related:

1. Have a diagnosis of MM based on standard criteria

2. Currently has MM with measurable disease, defined as a monoclonal immunoglobulin
spike on serum electrophoresis of at least 0.5 gm/dL and/or urine monoclonal
immunoglobulin amount of at least 200 mg/24 hours.

3. Have relapsed within 12 weeks of receiving or is refractory to their most recent
bortezomib-containing regimen as long as they meet the following criteria:

- Progressed from bortezomib-containing regimen either as a single agent or in
combination with an alkylating agent (melphalan or cyclophosphamide), an
anthracycline (doxorubicin or pegylated liposomal doxorubicin), IMiDs
(thalidomide or lenalidomide), and/or a glucocorticosteroid (prednisone,
dexamethasone or medrol)

- Bortezomib must have been administered at 4 doses of a minimum of 1.0 mg/m2 in
no more than 28 days per cycle. Subjects must have received at least one cycle
meeting this definition and have shown progressive disease to be considered
eligible.

- Subject who have been refractory to their most recent bortezomib-containing
regimen are eligible regardless of when the subject received that regimen, as
long as they meet the above criteria and have been off the treatment for > 3
weeks.

Definition of refractory disease: patients who meet criteria for progressive disease
while currently receiving treatment.

Demographics:

4. Age ≥ 18 years

5. Life expectancy ≥ 3 months

6. ECOG performance status 0-2 at study entry

Laboratory tests (within 14 days prior to drug dosing on Cycle 1, Day 1)

7. Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L; if the bone marrow is extensively
infiltrated (> 70% plasma cells) then 1.0 x 109/L

8. Hemoglobin ≥ 8 g/dL (subjects may be receiving red blood cell [RBC] transfusions in
accordance with institutional guidelines)

9. Platelet count ≥ 75 × 109/L; if the bone marrow is extensively infiltrated (> 70%
plasma cells) then 50 x 10^9/L

10. Creatinine clearance (CrCl) ≥ 30 mL/minute either measured or calculated. Subject
with a creatinine > 15mL/min and < 30 mL/min due to significant myelomatous
involvement of the kidneys may be enrolled in the study after receipt of approval
from Oncotherapeutics.

11. Adequate hepatic function, with AST (SGOT) and ALT (SGPT) 3 x upper limit of normal
(ULN) or 5 x ULN if hepatic metastases are present and serum total bilirubin ≤ 1.5 x
ULN

12. Serum potassium > 3 and < 5

Ethical/Other

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

14. Females of childbearing potential (FCBP) must agree to ongoing pregnancy testing and
to practice contraception.

15. Male subjects must agree to practice contraception.

Exclusion:

Disease-related

1. Plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal
protein (M-protein) and skin changes (POEMS) syndrome

2. Plasma cell leukemia

3. Severe hypercalcemia, i.e., serum calcium 12 mg/dL (3.0 mmol/L) corrected for albumin

4. Received the following prior therapy:

- Chemotherapy within 21 days of enrollment (6 wks for nitrosoureas)

- Corticosteroids (>10 mg/day prednisone or equivalent) within 21 days of
enrollment

- Immunotherapy or antibody therapy as well as thalidomide, lenalidomide, arsenic
trioxide, or bortezomib within 21 days before enrollment

- Radiation therapy within 21 days before enrollment, receipt of localized
radiation therapy does not preclude enrollment

- Use of any other experimental drug or therapy within 28 days of enrollment

Concurrent Conditions

5. Impaired cardiac function or clinically significant cardiac diseases, including any
one of the following:

- Unstable angina or myocardial infarction within 4 months prior to enrollment

- NYHA Class III or IV heart failure

- Uncontrolled angina

- Clinically significant pericardial 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. Prior to study entry, any ECG
abnormality at Screening has to be documented by the investigator as not
medically relevant.

6. Pregnant or lactating females

7. Major surgery within 28 days prior to enrollment or has not recovered from side
effects of such therapy (Kyphoplasty is not considered to be a major surgical
procedure; however, the investigator is to discuss enrollment of a patient with a
recent history of kyphoplasty with Oncotherapeutics).

8. Acute active infection requiring treatment with systemic antibiotics, antivirals, or
antifungals within 14 days prior to receiving first dose of study drug

9. Known human immunodeficiency virus infection; baseline testing is not required

10. Active hepatitis B or C infection; baseline testing is not required

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

12. Nonhematologic malignancy within the past 5 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

13. Concurrent use of other anti-cancer agents or treatments

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

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

16. Subjects with pleural effusions requiring thoracentesis or ascites requiring
paracentesis within 14 days prior to enrollment

17. 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