Study of the Safety and Pharmacokinetics of Carfilzomib in Patients with Relapsed and Refractory Multiple Myeloma and Varying Degrees of Renal Function

1. Written informed consent in accordance with federal, local, and institutional guidelines 2. Males and females ≥ 18 years of age 3. Multiple Myeloma 4. Documented relapsed or progressive disease (PD) after receiving at least two prior treatment regimens (induction therapy with autologous stem cell transplant and maintenance is considered a single regimen), and must have achieved a minimal response or better to at least one of the regimens 5. Current measurable disease, as indicated by one or more of the following: • Serum M-protein ≥ 0.5 g/dL • Urine M-protein ≥ 200 mg/24 hours • Serum Free Light Chain (FLC) assay: Involved FLC level ≥ 10 mg/dL provided serum FLC ratio is abnormal 6. Life expectancy of more than three months 7. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 8. Adequate hepatic function, with bilirubin < 2 times the upper limit of normal (ULN) and alanine aminotransferase (ALT) < 3 times ULN 9. Total white blood cell (WBC) count ≥ 2,000/mm³ 10. Absolute neutrophil count (ANC) ≥ 1,000/mm³ 11. Hemoglobin ≥ 7 gm/dL •Subjects may receive red blood cell (RBC) transfusions or supportive care with erythropoietin or darbepoetin in accordance with institutional guidelines 12. Platelet count ≥ 30,000/ mm³ 13. Female subjects of child-bearing potential must have a negative serum pregnancy test within seven days of the first dose and agree to use dual methods of contraception during and for 3 months following last dose of drug. Post menopausal females (> 45 years old and without menses for > 1 year) and surgically sterilized females are exempt from a pregnancy test 14. Male subjects must use an effective barrier method of contraception during study and for three months following the last dose if sexually active with a female of child-bearing potential

1. Glucocorticoid therapy in a dose equivalent to prednisone ≥ 20 mg/day within 14 days prior to first dose of study drug 2. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) 3. Plasma cell leukemia 4. Chemotherapy with approved or investigative anticancer therapeutics, including steroid therapy dose as defined above, within 14 days prior to first dose of study drug or antibody therapy within 6 weeks prior to first dose of study drug 5. Radiation therapy or immunotherapy within 3 weeks prior to first dose; localized radiation therapy within 1 week prior to first dose 6. Participation in an investigational therapeutic study within 14 days prior to first dose of study drug 7. Prior carfilzomib treatment 8. Pregnant or lactating females 9. Major surgery within 3 weeks prior to first dose of study drug 10. Congestive heart failure (New York Heart Association Class III to IV), symptomatic ischemia, conduction abnormalities or myocardial infarction in the three months prior to first dose of study drug 11. Uncontrolled hypertension 12. Recent history of acute active infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to first dose of study drug 13. Known or suspected human immunodeficiency virus (HIV) infection, known HIV seropositivity 14. Active hepatitis A, B, or C infection 15. Other malignancy within the past 3 years except a) adequately treated basal cell or squamous cell skin cancer, b) carcinoma in situ of the cervix, or c) prostate cancer < Gleason Grade 7 with stable prostate specific antigen (PSA) levels 16. Any clinically significant medical or psychiatric disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent 17. Significant neuropathy (Grade 3, Grade 4, or Grade 2 with pain) at the time of the first dose and/or within 14 days prior to enrollment 18. Subjects in whom the required program of oral hydration and intravenous fluid hydration is contraindicated, e.g., due to preexisting pulmonary or cardiac impairment 19. Subjects with pleural effusions requiring routine thoracentesis or ascites requiring routine paracentesis 20. Subjects with a known contraindication to receiving dexamethasone or allopurinol 21. Receipt of granulocyte- and granulocyte/ macrophage- colony stimulating factor (G-CSF and GM-CSF) within 1 week prior to first dose of study drug 22. Receipt of pegylated G-CSF within 2 weeks prior to first dose of study drug 23. RBC and platelet transfusions within 7 days prior to first dose of study drug 24. Subjects with known or suspected cardiac amyloidosis 25. Subjects with myelodysplastic syndrome 26. Subjects undergoing peritoneal dialysis