A Multicenter, Open-label, Phase 1b Study of Carfilzomib, Cyclophosphamide and Dexamethasone in Newly Diagnosed Multiple Myeloma SubjectsCHAMPION 2

1. Newly diagnosed multiple myeloma 2. Measurable disease, as defined by 1 or more of the following • Serum M-protein ≥ 0.5 g/dL, or • Urine M-protein ≥ 200 mg/24 hours, or • In subjects without detectable serum or urine M-protein, serum free light chain (SFLC) > 100 mg/L (involved light chain) and an abnormal kappa lambda ( κ/λ) ratio 3. Males and females ≥ 18 years of age 4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 5. Adequate hepatic function 6. Left ventricular ejection fraction (LVEF) ≥ 40% 7. Absolute neutrophil count (ANC) ≥ 1.0 × 10^9/L 8. Platelet count ≥ 50 × 10^9/L 9. Calculated or measured creatinine clearance (CrCl) of ≥ 15 mL/min

1. Planned autologous hematopoietic stem cell transplantation (HSCT) for the initial therapy of newly diagnosed multiple myeloma 2. Multiple myeloma of immunoglobulin M (IgM) subtype 3. Prior systemic treatment for multiple myeloma 4. Glucocorticoid therapy within 14 days prior to enrollment that equals or exceeds the equivalent of dexamethasone 160 mg 5. Known amyloidosis 6. Active congestive heart failure (New York Heart Association [NYHA] Class III to IV), symptomatic ischemia, or conduction abnormalities uncontrolled by conventional intervention. Myocardial infarction within 6 months prior to enrollment. 7. Known human immunodeficiency virus (HIV) seropositive, hepatitis C infection, and/or hepatitis B (subjects with hepatitis B surface antigen [SAg] or core antibody receiving and responding to antiviral therapy directed at hepatitis B are allowed) 8. Significant neuropathy (Grades ≥ 2) within 14 days prior to enrollment 9. 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