Study of the Safety and Pharmacokinetics of Carfilzomib in Patients With Relapsed and Refractory Multiple Myeloma and Varying Degrees of Renal Function
Condition: Multiple Myeloma; Renal Insufficiency
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Renal Insufficiency
Intervention: Carfilzomib
Intervention description: Carfilzomib was administered intravenously (IV) at a rate of approximately 10 mL/minute.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Myeloma; Renal Insufficiency; Proteasome; Hematological; carfilzomib; PR-171

Summary:

      The purpose of this study is to assess the influence of renal impairment on carfilzomib in
      patients with Multiple Myeloma (MM).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Written informed consent in accordance with federal, local, and institutional
             guidelines

          2. Males and females ≥ 18 years of age

          3. Multiple Myeloma

          4. Documented relapsed or progressive disease (PD) after receiving at least two prior
             treatment regimens (induction therapy with autologous stem cell transplant and
             maintenance is considered a single regimen), and must have achieved a minimal response
             or better to at least one of the regimens

          5. Current measurable disease, as indicated by one or more of the following:

               -  Serum M-protein ≥ 0.5 g/dL

               -  Urine M-protein ≥ 200 mg/24 hours

               -  Serum Free Light Chain (FLC) assay: Involved FLC level ≥ 10 mg/dL provided serum
                  FLC ratio is abnormal

          6. Life expectancy of more than three months

          7. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2

          8. Adequate hepatic function, with bilirubin < 2 times the upper limit of normal (ULN)
             and alanine aminotransferase (ALT) < 3 times ULN

          9. Total white blood cell (WBC) count ≥ 2,000/mm³

         10. Absolute neutrophil count (ANC) ≥ 1,000/mm³

         11. Hemoglobin ≥ 7 gm/dL

               -  Subjects may receive red blood cell (RBC) transfusions or supportive care with
                  erythropoietin or darbepoetin in accordance with institutional guidelines

         12. Platelet count ≥ 30,000/ mm³

         13. 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

         14. Male subjects must use an effective barrier method of contraception during study and
             for three months following the last dose if sexually active with a female of
             child-bearing potential

        Exclusion Criteria:

          1. Glucocorticoid therapy in a dose equivalent to prednisone ≥ 20 mg/day within 14 days
             prior to first dose of study drug

          2. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and
             skin changes)

          3. Plasma cell leukemia

          4. Chemotherapy with approved or investigative anticancer therapeutics, including steroid
             therapy dose as defined above, within 14 days prior to first dose of study drug or
             antibody therapy within 6 weeks prior to first dose of study drug

          5. Radiation therapy or immunotherapy within 3 weeks prior to first dose; localized
             radiation therapy within 1 week prior to first dose

          6. Participation in an investigational therapeutic study within 14 days prior to first
             dose of study drug

          7. Prior carfilzomib treatment

          8. Pregnant or lactating females

          9. Major surgery within 3 weeks prior to first dose of study drug

         10. Congestive heart failure (New York Heart Association Class III to IV), symptomatic
             ischemia, conduction abnormalities or myocardial infarction in the three months prior
             to first dose of study drug

         11. Uncontrolled hypertension

         12. Recent history of acute active infection requiring systemic antibiotics, antivirals,
             or antifungals within two weeks prior to first dose of study drug

         13. Known or suspected human immunodeficiency virus (HIV) infection, known HIV
             seropositivity

         14. Active hepatitis A, B, or C infection

         15. Other malignancy within the past 3 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 7 with stable prostate specific antigen (PSA) levels

         16. Any clinically significant medical or psychiatric disease or condition that, in the
             Investigator's opinion, may interfere with protocol adherence or a subject's ability
             to give informed consent

         17. Significant neuropathy (Grade 3, Grade 4, or Grade 2 with pain) at the time of the
             first dose and/or within 14 days prior to enrollment

         18. Subjects in whom the required program of oral hydration and intravenous fluid
             hydration is contraindicated, e.g., due to preexisting pulmonary or cardiac impairment

         19. Subjects with pleural effusions requiring routine thoracentesis or ascites requiring
             routine paracentesis

         20. Subjects with a known contraindication to receiving dexamethasone or allopurinol

         21. Receipt of granulocyte- and granulocyte/ macrophage- colony stimulating factor (G-CSF
             and GM-CSF) within 1 week prior to first dose of study drug

         22. Receipt of pegylated G-CSF within 2 weeks prior to first dose of study drug

         23. RBC and platelet transfusions within 7 days prior to first dose of study drug

         24. Subjects with known or suspected cardiac amyloidosis

         25. Subjects with myelodysplastic syndrome

         26. Subjects undergoing peritoneal dialysis