Once-weekly Versus Twice-weekly Carfilzomib in Combination With Dexamethasone in Adults With Relapsed and Refractory Multiple Myeloma

Exclusion Criteria

• •1. Waldenström macroglobulinemia
• •2. Multiple myeloma of Immunoglobin M (IgM) subtype
• •3. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
• •4. Plasma cell leukemia (\> 2.0 × 10⁹/L circulating plasma cells by standard differential)
• •5. Myelodysplastic syndrome
• •6. Second malignancy within the past 5 years except:
• •* Adequately treated basal cell or squamous cell skin cancer
• •* Carcinoma in situ of the cervix
• •* Prostate cancer \< Gleason score 6 with stable prostate-specific antigen (PSA) over 12 months
• •* Ductal breast carcinoma in situ with full surgical resection (i.e., negative margins)
• •* Treated medullary or papillary thyroid cancer
• •* Similar condition with an expectation of \> 95% five-year disease-free survival
• •7. History of or current amyloidosis
• •8. Cytotoxic chemotherapy within the 28 days prior to randomization
• •9. Immunotherapy within the 21 days prior to randomization
• •10. Glucocorticoid therapy within the 14 days prior to randomization that exceeds a cumulative dose of 160 mg of dexamethasone or 1000 mg prednisone
• •11. Radiation therapy:
• •* Focal therapy within the 7 days prior to randomization
• •* Extended field therapy within the 21 days prior to randomization
• •12. Prior treatment with either carfilzomib or oprozomib
• •13. Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib)
• •14. Contraindication to dexamethasone or any of the required concomitant drugs or supportive treatments, including hypersensitivity to antiviral drugs, or intolerance to hydration due to pre-existing pulmonary or cardiac impairment
• •15. Active congestive heart failure (New York Heart Association \[NYHA\] Class III or IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, acute diffuse infiltrative pulmonary disease, pericardial disease, or myocardial infarction within 6 months prior to enrollment
• •16. Active infection within the 14 days prior to randomization requiring systemic antibiotics
• •17. Pleural effusions requiring thoracentesis within the 14 days prior to randomization
• •18. Ascites requiring paracentesis within the 14 days prior to randomization
• •19. Ongoing graft-versus-host disease
• •20. Uncontrolled hypertension or uncontrolled diabetes despite medication
• •21. Significant neuropathy (≥ Grade 3) within the 14 days prior to randomization
• •22. Known cirrhosis