Clinical trial NCT00511238 (phase 2, status: completed)
Conditions: multiple myeloma
ICD codes: C90.01, C90.02, C90.00
Drugs: carfilzomib, carfilzomib
SMILES: CC(C)C[C@H](NC(=O)[C@H](CCC1=CC=CC=C1)NC(=O)CN1CCOCC1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(=O)[C@@]1(C)CO1, CC(C)C[C@H](NC(=O)[C@H](CCC1=CC=CC=C1)NC(=O)CN1CCOCC1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(=O)[C@@]1(C)CO1
Eligibility criteria:

        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.

        Exclusion Criteria:

          -  Disease Related

               -  Multiple Myeloma IgM (A1 Only)

               -  Subjects who failed to achieve at least a confirmed MR(≥ 25% reduction in
                  M-protein for ≥ 6 weeks) (A1 Only)

               -  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
                  (A1 Only)

               -  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 cardiac ischemia, cardiomyopathy, conduction abnormalities
                  uncontrolled by conventional intervention, or myocardial infarction in the
                  previous six months, LVEF < 40

               -  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
                  (A1 Only)

               -  Subjects with known or suspected amyloidosis (A1 Only)

               -  Subjects with pleural effusions requiring thoracentesis or ascites requiring
                  paracentesis (A1 Only)

               -  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 (A1 Only)

          -  Ethical / Other

               -  Female subjects who are pregnant or lactating

               -  Serious psychiatric or medical conditions that could interfere with treatment