Phase 2 Study of Carfilzomib in Relapsed Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: carfilzomib
Intervention description: Intravenous (IV) injection over 2 to 10 minutes twice weekly for three weeks followed by 12 days of rest.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 164.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      To evaluate the best overall response rate, safety and tolerability of carfilzomib in
      patients with relapsed or refractory multiple myeloma.
    

Eligibility criteria:

        Inclusion Criteria:

        Disease Related

          -  Multiple myeloma

          -  Subjects must have measurable disease, defined as one or more of the following:

               -  Serum M-protein ≥ 1 g/dL

               -  Urine M-protein ≥ 200 mg/24 hours

          -  Subjects must have been responsive (i.e., achieve a minimal response [MR] or better)
             to standard, first line therapy

          -  Relapsed and/or refractory or progressive disease after at least one, but no more than
             three, prior therapeutic treatments or regimens for multiple myeloma. Refractory
             disease is defined as ≤ 25% response or progression during therapy or within 60 days
             after completion of therapy. Induction therapy and stem cell transplant will be
             considered as one regimen

        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 < 2.0 times the upper limit of normal, and
             aspartate aminotransferase (AST) and alanine aminotransferase (ALT) of < 3.0 times the
             upper limit of normal

          -  Uric acid, if elevated, must be corrected to within laboratory normal range prior to
             dosing

          -  Total white blood cell (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 absolute neutrophil count (ANC) should be independent of granulocyte colony
             stimulating factor (G-CSF) or granulocyte macrophage colony stimulating factor
             (GM-CSF) support for ≥ 1 week and of pegylated G-CSF for ≥ 2 weeks

          -  Subjects may receive red blood cell (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)].
             Multiply result by 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

          -  Multiple Myeloma Immunoglobulin M (IgM)

          -  Subjects previously treated with any proteasome inhibitor (for Part 2 Proteasome
             Inhibitor - Naïve only, criteria added at Amendment 2)

          -  Subjects must not be primary refractory to standard first-line therapy

          -  Subjects with non-secretory multiple myeloma, defined as < 1 g/dL M-protein in serum,
             < 200 mg/24 hour 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 first dose, 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 human immunodeficiency (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 prostate-specific antigen (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 known contraindication to receiving allopurinol

          -  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