A Study of Carfilzomib vs Best Supportive Care in Subjects With Relapsed and Refractory Multiple Myeloma

Inclusion Criteria

• Multiple myeloma
• Measurable disease based on central laboratory values, as defined by one or both of the following criteria (assessed within 21 days prior to randomization):
• Serum M-protein
• Serum protein electrophoresis (SPEP): ≥ 0.5 g/dL
• For immunoglobulin A (IgA) patients whose disease can only be reliably measured by serum quantitative immunoglobulin (qIgA): > 750 mg/dL (0.75 g/dL)
• Urine Bence Jones protein: ≥ 200 mg/24 h
• Responsive (defined as a 25% or greater decrease in M-protein or total protein) to at least one line of prior therapy
• Relapsed multiple myeloma, defined as disease progression while on or after at least 1 prior treatment regimen
• Refractory multiple myeloma, defined as meeting one or more of the following:
• Nonresponsive to most recent therapy (eg, stable disease only, or progressive disease while on treatment)
• Disease progression within 60 days of discontinuation from most recent therapy
• Received 3 or more prior therapeutic regimens for multiple myeloma
• Adequate prior treatment with bortezomib (if less than 4 complete cycles, the reason for discontinuation must be reviewed by the Medical Monitor and the reason documented)
• Prior treatment with an immunomodulatory agent (lenalidomide, if available, and/or thalidomide)
• Prior treatment with an alkylating agent (standard or high-dose)
• Prior treatment with a corticosteroid
• Criterion no longer applicable (with Amendment 2, Criterion 11, the requirement of "prior treatment with an anthracycline unless not clinically indicated" is removed.)
• Age ≥ 18 years
• Life expectancy of at least 1 month
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Adequate hepatic function, with serum alanine aminotransferase (ALT) 45 years old and without menses for > 1 year) and surgically sterilized females are exempt from these requirements. Male patients must use an effective barrier method of contraception during the study and for 3 months following the last dose if sexually active with a female of childbearing potential.

Exclusion Criteria

• Waldenström's macroglobulinemia or IgM myeloma
• Refractory to all prior therapies
• Disease measurable only by serum free light chain assay (SFLC)
• POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
• Plasma cell leukemia (> 2.0 × 10^9/L circulating plasma cells by standard differential)
• Prior carfilzomib treatment
• Chemotherapy (approved or investigational) within 14 days prior to randomization
• Immunotherapy or antibody therapy within 28 days prior to randomization
• Corticosteroid therapy at a dose equivalent to dexamethasone > 4 mg/day within 14 days prior to randomization
• Radiotherapy within 7 days prior to randomization
• Major surgery within 21 days prior to randomization
• Congestive heart failure (NYHA Class III or IV) or symptomatic cardiac ischemia, conduction system abnormalities uncontrolled by conventional intervention (conduction abnormalities not clinically warranting intervention are allowed)
• Myocardial infarction in the previous 3 months
• Acute active infection requiring systemic treatment (antibiotics, antivirals, or antifungals) within 14 days prior to randomization
• Known human immunodeficiency virus seropositivity
• Active hepatitis A, B, or C infection
• Other 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, vulva, or breast; c) prostate cancer of Gleason Score 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, carcinoma in situ of the breast, or benign tumors of the adrenal or pancreas
• Significant neuropathy (Grades 3-4