Phase 2 Study of Carfilzomib in Relapsed and Refractory Multiple Myeloma

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
• •* Serum FLC ≥ 10 mg/dL with abnormal ratio (A0 Only)
• •* Quantitative immunoglobulin levels using nephelometry or turbidometry (only if protein electrophoresis was felt to be unreliable for M-protein measurement) (A0 Only)
• •* 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 (A1 Only)
• •* 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 with other myeloma treatments (history of stem cell transplant is acceptable) (A1 Only)
• •* Subjects must have received an anthracycline either alone or in combination with other myeloma treatments, unless not clinically indicated (A1 Only)
• •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 within normal range (A0 Only)
• •* Total white blood cell (WBC) count ≥ 2.0 × 109/L, absolute neutrophil count (ANC) ≥ 1.0 × 109/L, hemoglobin ≥ 8.0 g/dL, and platelet count ≥ 50.0 × 109/L (A0 Only)
• •* Absolute neutrophil count \> 1,000/mm3, hemoglobin \> 8.0 g/dL, and platelet count \> 50,000/mm3 (A1 Only)
• •* 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.