Carfilzomib in Combination With Dexamethasone (Kd) in Chinese Patients With Relapsed & Refractory Multiple Myeloma
Condition: Relapsed and Refractory Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Dexamethasone; Carfilzomib
Intervention description: 20 mg intravenous (IV) or oral dexamethasone on days 1, 2, 8, 9, 15, 16, 22, and 23 in 28-day cycles.; Infusion of IV carfilzomib on days 1, 2, 8, 9, 15 and 16 in each 28-day cycle.
Intervention MeSH terms: Dexamethasone
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 126.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to evaluate the safety, tolerability and overall response rate
      of carfilzomib in combination with dexamethasone for the treatment of multiple myeloma in
      China.
    

Eligibility criteria:

        Inclusion Criteria: - 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 -- In subjects without measurable serum or urine M-protein, serum free light chain
        (SFLC) > 100 mg/L (involved light chain) and an abnormal κ/λ ratio - Subjects must have
        been responsive (ie, achieved a minimal response [MR] or better) to at least one of their
        prior treatment regimens - Refractory to the most recently received therapy. Refractory
        disease defined as ≤ 25% response to, or progressing during therapy or within 60 days after
        completion of therapy - Subjects must have received ≥ 2 prior regimens. Induction therapy
        and stem cell transplant (± maintenance) will be considered as 1 regimen - Subjects must
        have received prior treatment with bortezomib and an immunomodulatory drug - Subjects must
        have received an alkylating agent or anthracycline alone or in combination with other
        myeloma treatments (this may include high dose melphalan as part of the conditioning
        regimen prior to a stem cell transplant) - Males and females ≥ 18 years of age - Life
        expectancy of more than 3 months - Eastern Cooperative Oncology Group (ECOG) Performance
        Status of 0-2 - Adequate hepatic function, with bilirubin < 2.0 times the upper limit of
        normal (ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3.0
        times the ULN - Absolute neutrophil count (ANC) ≥ 1,000/mm³, hemoglobin ≥ 8.0 g/dL, and
        platelet count ≥ 50,000/mm³ • Subjects should not have received platelet transfusions for
        at least 1 week prior to obtaining the screening platelet count • Screening ANC should be
        independent of granulocyte colony stimulating factor (G-CSF) or granulocyte macrophage
        colony stimulating factor (GM-CSF) support for ≥ 1 week and pegylated G-CSF for ≥ 2 weeks •
        Use of erythropoietic stimulating factors and red blood cell (RBC) transfusions per
        institutional guidelines is allowed; however, most recent RBC transfusion may not have been
        done within 7 days prior to obtaining screening hemoglobin - Calculated or measured
        creatinine clearance (CrCl) of ≥ 30 mL/min. Calculated CrCl should be performed by using a
        widely accepted equation (eg, the Cockcroft and Gault equation): ([140 - Age] × Mass [kg] /
        [72 × Creatinine mg/dL]). Multiply the result by 0.85 if the subject is female. - Left
        ventricular ejection fraction (LVEF) ≥ 40%; 2-dimensional transthoracic echocardiogram
        (ECHO) is the preferred method of evaluation; multiple gated acquisition scan (MUGA) is
        acceptable if ECHO is not available - Written informed consent in accordance with federal,
        local, and institutional guidelines - Female subjects of child-bearing potential (FCBP)
        must have a negative serum pregnancy test within 21 days prior to enrollment and agree to
        use an effective method of contraception during and for 30 days following last dose of
        carfilzomib. This protocol defines a FCBP as a sexually mature woman who: 1) has not
        undergone a hysterectomy, bilateral oophorectomy, or bilateral salpingectomy, or 2) has not
        been naturally postmenopausal for at least 24 consecutive months (ie, has had menses at any
        time in the preceding 24 consecutive months) - Male subjects must use an effective barrier
        method of contraception during the study and for 3 months following the last dose of
        carfilzomib if sexually active with a FCBP. Male subjects must not donate sperm during
        treatment and for an additional 90 days after last dose of carfilzomib. Male subjects with
        pregnant partners must practice sexual abstinence or use a condom during vaginal sex.
        Exclusion Criteria: - Waldenström's macroglobulinemia or immunoglobulin M (IgM) multiple
        myeloma - Subjects who failed to achieve at least a confirmed MR on any of their prior
        regimens - Subjects with non-secretory multiple myeloma, defined as < 1 g/dL M-protein in
        serum and < 200 mg/24 hour M-protein in urine and SFLC ≤ 100 mg/L (involved light chain) -
        Glucocorticoid therapy (prednisone > 10 mg/day or equivalent) within 3 weeks prior to Cycle
        1 Day 1 - POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein,
        and skin changes) - Plasma cell leukemia (> 2.0 × 10⁹/L circulating plasma cells by
        standard differential) - Chemotherapy with approved or investigative anticancer
        therapeutics including steroid therapy within the 3 weeks prior to Cycle 1 Day 1 -
        Radiation therapy or immunotherapy in the 4 weeks prior to Cycle 1 Day 1; localized
        radiation therapy within 1 week prior to Cycle 1 Day 1 - Participation in an
        investigational therapeutic study within 3 weeks or within 5 drug half-lives (T½) prior to
        Cycle 1 Day 1, whichever time is greater - Prior treatment with carfilzomib - Major surgery
        within 3 weeks before Cycle 1 Day 1 - Congestive heart failure (CHF; New York Heart
        Association Class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled
        by conventional intervention, or myocardial infarction within 6 months - Uncontrolled
        hypertension (a sustained systolic blood pressure > 140 mmHg and/or diastolic blood
        pressure > 90 mmHg) - Acute active infection requiring systemic antibiotics, antivirals, or
        antifungals within 2 weeks prior to Cycle 1 Day 1 - Known human immunodeficiency virus
        (HIV) seropositive, hepatitis C infection, and/or hepatitis B (except for patients with
        hepatitis B surface antigen or core antibody receiving and responding to antiviral therapy
        directed at hepatitis B: these patients are allowed) - Non-hematologic malignancy within
        the past 3 years except: -- Adequately treated basal cell or squamous cell skin cancer, --
        Carcinoma in situ of the cervix, or -- Prostate cancer < Gleason Score 6 with stable
        prostate-specific antigen - Subjects with treatment-related myelodysplastic syndrome -
        Significant neuropathy (Grade 3, 4, or Grade 2 with pain) at the time of baseline
        evaluation - Subjects in whom the required program of fluid hydration is contraindicated,
        eg, due to pre-existing pulmonary, cardiac, or renal impairment - Subjects with known or
        suspected amyloidosis - Subjects with pleural effusions requiring thoracentesis - Subjects
        with 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 - Female subjects who are pregnant or lactating,
        or planning to become pregnant during treatment and for an additional 30 days after
        discontinuing carfilzomib. - Serious psychiatric or medical conditions that could interfere
        with treatment