Study of Weekly Carfilzomib, Cyclophosphamide and Dexamethasone In Newly Diagnosed Multiple Myeloma Patients (wCCyd)

Inclusion Criteria: Disease-related 1. Patient is a newly diagnosed MM patient. 2. Patient is age ≥ 65 year of age or who are ineligible for autologous stem cell transplantation. 3. Patient has measurable disease, defined as follows: any quantifiable serum monoclonal protein value (generally, but not necessarily, ≥ 0.5 g/dL of M-protein) and, where applicable, urine light-chain excretion of \> 200 mg/24 hours. For patients with oligo- or non-secretory MM, it is required that they have measurable plasmacytoma \> 2 cm as determined by clinical examination or applicable radiographs (i.e. MRI, CT-Scan) or an abnormal free light chain ratio (n.v.: 0.26-1.65). We anticipate that less than 10% of patients admitted to this study will be oligo- or non-secretory MM with free light chains only in order to maximize interpretation of benefit results. Demographic: 4. Age ≥ 18 years. 5. Life expectancy ≥ 3 months. 6. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Appendix F). Laboratory: 7. 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 14 days prior to randomization. 8. Absolute neutrophil count (ANC) ≥ 1.0 × 109/L within 14 days prior to randomization. 9. Corrected serum calcium ≤ 14 mg/dL (3.5 mmol/L). 10. Alanine transaminase (ALT): ≤ 3 x the ULN. 11. Hemoglobin ≥ 8 g/dL (80 g/L) within 14 days prior to randomization (subjects may be receiving red blood cell \[RBC\] transfusions in accordance with institutional guidelines). 12. Platelet count ≥ 50 × 109/L (≥ 30 × 109/L if myeloma involvement in the bone marrow is \> 50%) within 14 days prior to randomization. 13. Creatinine clearance (CrCl) ≥ 15 mL/minute within 7 days prior to randomization, either measured or calculated using a standard formula (eg, Cockcroft and Gault). Ethical/Other: 14. Written informed consent in accordance with federal, local, and institutional guidelines. 15. Females of childbearing potential (FCBP) must agree to ongoing pregnancy testing and to practice contraception. 16. Male subjects must agree to practice contraception. Exclusion Criteria: Disease-related: 1. Previous treatment with anti-myeloma therapy (does not include radiotherapy, bisphosphonates, or a single short course of steroid; ≤ to the equivalent of dexamethasone 40 mg/day for 4 days) 2. Patient with relapsed or refractory multiple myeloma. 3. Patients with non-secretory MM unless serum free light chains are present and the ratio is abnormal. Concurrent Conditions: 4. Pregnant or lactating females (Appendix I). 5. Major surgery within 21 days prior to randomization. 6. Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to randomization. 7. Known human immunodeficiency virus infection. 8. Active hepatitis B or C infection. 9. Unstable angina or 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. 10. Uncontrolled hypertension, uncontrolled congestive heart failure (CHF) or uncontrolled diabetes within 14 days prior to randomization. 11. Non-hematologic malignancy 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. 12. Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 14 days prior to randomization. 13. Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib). 14. 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. 15. Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to randomization. 16. 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.