NCT00530816已完成2 期
An Open-label, Single-arm, Phase 2 Study of Carfilzomib in Patients With Relapsed or Refractory Multiple Myeloma
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 164
- 试验地点
- 30
- 主要终点
- Best Overall Response Rate (ORR) in the Response Evaluable Subset Population
研究概览
简要总结
To evaluate the best overall response rate, safety and tolerability of carfilzomib in patients with relapsed or refractory multiple myeloma.
详细描述
Two groups of patients with multiple myeloma were initially studied: bortezomib-naïve and bortezomib-treated. Following Amendment 2, only bortezomib-naïve patients were enrolled. Study results were reported in 2 parts, depending on whether a patient received prior bortezomib.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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.
排除标准
- •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
研究组 & 干预措施
Carfilzomib
Experimental
Participants received carfilzomib 20 mg/m² intravenous (IV) injection on Days 1, 2, 8, 9, 15, and 16, in 28-day treatment cycles for a maximum of 12 cycles.
Starting with Amendment 3, if all doses in Cycle 1 were well-tolerated the dose was escalated to 27 mg/m² IV for subsequent cycles.
干预措施: carfilzomib (Drug)
结局指标
主要结局
Best Overall Response Rate (ORR) in the Response Evaluable Subset Population
时间窗: Disease response was assessed on Day 15 of Cycle 1, Day 1 of Cycles 2 through 12, and at End of Study, 30 days after last dose. Median duration of treatment was 100 days for Part 1 and 170 days for Part 2 participants.
ORR is defined as the percentage of patients who achieved a best response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR) determined by Independent Review Committee (IRC). Responses were assessed according to International Uniform Response Criteria for Multiple Myeloma, documented by 2 consecutive assessments made at any time before the start of new therapy. sCR: CR as defined below plus normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence. CR: absence of M-protein in serum and urine by immunofixation, disappearance of any soft tissue plasmacytomas, and ≤5% plasma cells in bone marrow. VGPR: serum and urine M-proteins detectable by immunofixation but not by electrophoresis or a ≥ 90% reduction in serum M-protein with urine M-protein level \< 100 mg/24 hours. PR: ≥ 50% reduction of serum M-protein and in urine of ≥ 90% or to \< 200 mg per 24 hours.
次要结局
- Time to Progression (TTP)(Patients were followed for up to 2 years after study discontinuation. The data cutoff for the analysis is 30 November 2010 for Part 1 and 22 April 2011 for Part 2. Median follow-up time was 13.4 months for Part 1 and 11.5 months in Part 2.)
- Progression-free Survival (PFS)(Patients were followed for up to 2 years after study discontinuation. The data cutoff for the analysis is 30 November 2010 for Part 1 and 22 April 2011 for Part 2. Median follow-up time was 13.4 months for Part 1 and 11.5 months in Part 2.)
- Overall Survival (OS)(Patients were followed for up to 2 years after study discontinuation. The data cutoff for the analysis is 19 November 2012 for Part 1 and 07 January 2013 for Part 2. Median follow-up time was 19.1 months for Part 1 and 35.9 months in Part 2.)
- Best Overall Response Rate (ORR) in the Response Evaluable Population(Disease response was assessed on Day 15 of Cycle 1, Day 1 of Cycles 2 through 12, End of Study, 30 days after last dose; median duration of treatment was 100 days for Part 1 and 170 days for Part 2 participants.)
- Clinical Benefit Rate (CBR)(Disease response was assessed on Day 15 of Cycle 1, Day 1 of Cycles 2 through 12, and at End of Study, 30 days after last dose. Median duration of treatment was 100 days for Part 1 and 170 days for Part 2 participants.)
- Duration of Response (DOR)(Patients were followed for up to 2 years after study discontinuation. The data cutoff for the analysis is 30 November 2010 for Part 1 and 22 April 2011 for Part 2.)
研究者
研究点 (30)
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