Inclusion Criteria:

• Disease Related

  • Multiple myeloma

  • Subjects must have measurable disease defined as one of the following:

    • Serum M-protein ≥ 1 g/dL
    • Urine M-protein ≥ 200 mg/24 hours
  • Subjects must have been responsive (i.e., achieved an MR or better) to first-line, standard of care therapy
  • Refractory to the most recently received therapy. Refractory disease is defined as ≤ 25% response or progression during therapy or within 60 days after completion of therapy.
  • Subjects must have received ≥ 2 prior regimens for relapsed disease. Induction therapy and stem cell transplant will be considered as one regimen
  • Subjects must have received prior treatment with bortezomib, and either thalidomide or lenalidomide
  • Subjects must have received an alkylating agent either alone or in combination wiht other myeloma treatments (history of stem cell transplant is acceptable)
  • Subjects must have received an anthracycline either alone or in combination with other myeloma treatments, unless not clinically indicated

• Demographic

  • Males and females > 18 years of age
  • Life expectancy of more than three months
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2

• Laboratory

  • Adequate hepatic function, with bilirubin less than 2.0 times the upper limit of normal, and AST and ALT of less than 3.0 times the upper limit of normal
  • Absolute neutrophil count > 1,000/mm3, hemoglobin > 8.0 g/dL, and platelet count > 50,000/mm3
  • Subjects should be platelet transfusion independent
  • Screening ANC should be independent of G-CSF or GM-CSF support for ≥ 1 week and of pegylated G-CSF for ≥ 2 weeks
  • Subjects may receive red blood cell (RBC) or platelet transfusions or receive supportive care such as erythropoietin and darbepoetin in accordance with institutional guidelines
  • Calculated and measured creatinine clearance of ≥ 30 mL/minute, calculated using the formula of Cockcroft and Gault [(140 - Age) X Mass (kg) / (72 X Creatinine mg/dL)]. Multiply result by 0.85 if female.

• Ethical / Other

  • Written informed consent in accordance with federal, local, and institutional guidelines
  • Female subjects of child-bearing potential must have a negative serum pregnancy test within seven days of the first dose and agree to use dual methods of contraception during and for 3 months following last dose of drug. Post menopausal females (> 45 years old and without menses for > 1 year) and surgically sterilized females are exempt from a pregnancy test. Male subjects must use an effective barrier method of contraception during study and for 3 months following the last dose if sexually active with a female of child-bearing potential.

Exclusion Criteria:

• Disease Related

  • Multiple Myeloma IgM
  • Subjects who failed to achieve at least a confirmed MR(≥ 25% reduction in M-protein for ≥ 6 weeks)
  • Subjects with non-secretory multiple myeloma, defined as < 1 g/dL M-protein in serum and < 200 mg/24 hr M-protein in urine
  • Subjects with disease measurable only by serum free light chain (SFLC) analysis
  • Glucocorticoid therapy (prednisone > 10 mg/day orally or equivalent) within the last three weeks
  • POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
  • Plasma cell leukemia
  • Chemotherapy with approved or investigative anticancer therapeutics including steroid therapy within the three weeks prior to first dose
  • Radiation therapy or immunotherapy in the previous four weeks; localized radiation therapy within 1 week prior to first dose
  • Participation in an investigational therapeutic study within three weeks or within five drug half-lives (t1/2) prior to Day 1, whichever time is greater
  • Prior treatment with carfilzomib

• Concurrent Conditions

  • Major surgery within three weeks before Day 1
  • Congestive heart failure (New York Heart Association class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction in the previous six months
  • Acute active infection requiring systemic antibiotics, antivirals or antifungals within 2 weeks prior to first dose
  • Known or suspected HIV infection or subjects who are HIV seropositive
  • Active hepatitis A,B,or C infection
  • Non-hematologic malignancy within the past three years except a) adequately treated basal cell or squamous cell skin cancer, b) carcinoma in situ of the cervix, or c) prostate cancer <Gleason Grade 6 with stable PSA
  • Subjects with treatment related myelodysplastic syndrome
  • Significant neuropathy (Grade 3, 4 or Grade 2 with pain) at the time of study initiation
  • Subjects in whom the required program of oral and intravenous fluid hydration is contraindicated, e.g., due to pre-existing pulmonary, cardiac or renal impairment
  • Subjects with known or suspected amyloidosis
  • Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis
  • Any 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

• Ethical / Other

  • Female subjects who are pregnant or lactating
  • Serious psychiatric or medical conditions that could interfere with treatment