Infusional Carfilzomib in Patients With Relapsed or Refractory Multiple Myeloma

Inclusion Criteria: * Participants must meet all of the following inclusion criteria to be eligible to enroll in this study. * Patients meeting the criteria for symptomatic multiple myeloma that has relapsed or is refractory to at least 2 prior lines of therapy. * Previous therapy with bortezomib. * Previous therapy with thalidomide or lenalidomide. * Patients must have measurable disease and therefore must have at least one of the following: Serum M-protein ≥1 gm/dL (≥10 gm/L) Urine M-protein ≥200 mg/24 hr Serum FLC assay: involved FLC ≥10 mg/dL (≥100 mg/L) provided serum FLC ratio is abnormal. * Age ≥ 18 years * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 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 enrollment * Absolute neutrophil count (ANC) ≥ 1.0 × 109/L within 14 days prior to enrollment Hemoglobin ≥ 8 g/dL (80 g/L) within 14 days prior to enrollment (participants may be receiving red blood cell \[RBC\] transfusions in accordance with institutional guidelines) * Platelet count ≥ 50 × 109/L (≥ 30 × 109/L if thought to be secondary to myeloma involvement of the bone marrow ) within 14 days prior to enrollment (platelet transfusions are allowed) * Creatinine clearance (CrCl) ≥ 15 mL/minute within 14 days prior to enrollment, either estimated or calculated using a standard formula (eg, Cockcroft and Gault) * Females of childbearing potential (FCBP) must agree to ongoing pregnancy testing and to practice contraception. * Male participants must agree to practice contraception. Exclusion Criteria: * Prior treatment with carfilzomib. * Known CNS involvement with myeloma * Pregnant or lactating females * Major surgery within 21 days prior to registration. * Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 7 days prior to enrollment * Known human immunodeficiency virus infection * Active hepatitis B or C infection * Unstable angina or myocardial infarction within 4 months prior to enrollment, NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless participant has a pacemaker * Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to enrollment. * Concurrent malignancies, except for treated non-melanoma skin cancer and cervical carcinoma in situ. * Significant neuropathy (Grades 3-4, ) within 14 days prior to enrollment * Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib) * Contraindication to any of the required concomitant drugs or supportive treatments, including options, antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment * Concurrent therapy with any other anticancer therapeutic with activity against multiple myeloma * Concurrent therapy with investigative agents (e.g., antibiotics or antiemetics)