Inclusion Criteria

Inclusion Criteria

1. Newly diagnosed, histologically confirmed, previously untreated Stage I, II, or III
multiple myeloma requiring systemic chemotherapy

2. Diagnosis of symptomatic multiple myeloma per IMWG uniform criteria within the past
90 days

3. Measurable disease, per IMWG criteria (>= one of the following) within the past 4
weeks:

- Monoclonal protein >= 0.5 g/dL by serum protein electrophoresis

- Monoclonal light chain >= 200 mg by 24-hour urine protein electrophoresis

- If serum protein electrophoresis is felt to be unreliable for routine M-protein
measurement, then quantitative immunoglobulin levels are acceptable

4. Life expectancy > 3 months

5. Eastern Cooperative Oncology Group (ECOG) performance status 0-2

6. Adequate hepatic function, with bilirubin < 1.5 x the ULN, and AST and ALT < 2.5 x
ULN

7. Absolute neutrophil count (ANC) >=1.0 x 109/L, hemoglobin >= 8 g/dL, platelet count
>= 75 x 109/L

8. Calculated creatinine clearance (by Cockroft-Gault) >= 60 ml/min

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

10. Subjects must agree to adhere to all study requirements, including birth control
measures and pregnancy testing, visit schedule, outpatient treatment, required
concomitant medications, and laboratory monitoring

11. Must be able to take either 81 mg or 325 mg aspirin daily as prophylactic
anticoagulation

Exclusion Criteria

1. Non-secretory or hyposecretory multiple myeloma, defined as <0.5 g/dL M-protein in
serum, <200 mg/24 hr urine M-protein, or disease only measured by serum free light
chain

2. POEMS syndrome

3. Plasma cell leukemia

4. Waldenström's macroglobulinemia or IgM myeloma

5. Radiotherapy to multiple sites or immunotherapy within 2 weeks before start of
protocol treatment (localized radiotherapy to a single site at least 1 week before
start is permissible)

6. Patient must not have been previously treated with any prior systemic therapy for the
treatment of multiple myeloma

- Prior treatment of hypercalcemia or spinal cord compression or aggressively
progressing myeloma with corticosteroids does not disqualify the patient (the
dose should not exceed the equivalent of 160 mg of dexamethasone in a 2 week
period)

- Bisphosphonates are permitted

7. Participation in an investigational therapeutic study within 3 weeks or within 5 drug
halflives (t1/2) prior to first dose, whichever time is greater

8. Pregnant or lactating females

9. History of allergy to mannitol

10. Major surgery within 3 weeks prior to first dose

11. Myocardial infarction within 3 months prior to enrollment, NYHA Class III or IV heart
failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or
electrocardiographic evidence of acute ischemia or active conduction system
abnormalities

12. Uncontrolled hypertension or diabetes

13. Acute active infection requiring systemic antibiotics, antivirals, or antifungals
within two weeks prior to first dose

14. Known or suspected HIV infection, known HIV seropositivity

15. Active hepatitis infection

16. Non-hematologic malignancy within the past 3 years except a) adequately treated basal
cell, squamous cell skin cancer, thyroid cancer, carcinoma in situ of the cervix, or
prostate cancer < Gleason Grade 6 with stable prostate specific antigen levels or
cancer considered cured by surgical resection alone

17. Any 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

18. Significant neuropathy (Grade >2) at the time of the first dose and/or within 14 days
before enrollment

19. Contraindication to any of the required concomitant drugs

20. Subjects in whom the required program of PO and IV fluid hydration is contraindicated

21. Subjects with known or suspected amyloidosis of any organ

22. Subjects with pleural effusions requiring thoracentesis or ascites requiring
paracentesis