• Clinical Benefit Response [ Time Frame: 2 to 12 months ] [ Designated as safety issue: No ]
  

• Safety and Tolerability, Clinical Benefit Response, Time to Progression, Duration of Response, Progression Free Survival, and best Overall Response Rate throughout the study [ Time Frame: 2 to 12 months ] [ Designated as safety issue: Yes ]
  

Drug: carfilzomib
IV push twice weekly for three weeks followed by 12 days of rest. 28 days = 1 cycle. A maximum of 12 cycles will be administered.

Inclusion Criteria:

• Disease Related

  • Multiple myeloma, IgG or IgA

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

    • Serum M-protein ≥ 1 g/dL
    • Urine M-protein ≥ 200 mg/24 hours
  • Relapsed multiple myeloma after a response to standard first-line chemotherapy or high-dose chemotherapy, and refractory to the most recent therapy. Refractory disease is defined as ≤ 25% response or progression during salvage therapy or within 60 days of completion of salvage therapy.
  • Subjects must have received prior treatment with bortezomib and either thalidomide or lenalidomide. Subjects may have received these agents in combination with other myeloma treatments.

• 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
  • Uric acid must be within laboratory normal range
  • Total WBC count > 2,000/mm3, 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
  • Subjects may receive RBC transfusion or receive supportive care such as erythropoietin and darbepoetin in accordance with institutional guidelines
  • Calculated or 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) X 0.85 (if female))
  • Serum creatinine ≤ 2 mg/dL

• 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.
  • Subjects must be able to receive outpatient treatment and laboratory monitoring at the institute that administers agent.

Exclusion Criteria:

• Disease Related

  • Subjects with non-secretory multiple myeloma, defined as <1 g/dL M-protein in serum, <200 mg/24 hr M-protein in urine, and less than 10 mg/dL involved serum FLC
  • 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 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 with recent history of acute infections requiring systemic treatment with antibiotics, antifungals or antivirals must have completed treatment two weeks prior to first dose

• Ethical / Other

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