NCT00721734已完成2 期
Phase 2 Study of the Safety and Pharmacokinetics of Carfilzomib in Subjects With Relapsed and Refractory Multiple Myeloma and Varying Degrees of Renal Function
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
- 50
- 试验地点
- 5
- 主要终点
- Clearance (CL) of Carfilzomib on Day 1 of Cycle 1
研究概览
简要总结
The purpose of this study is to assess the influence of renal impairment on carfilzomib in patients with Multiple Myeloma (MM).
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
- •Written informed consent in accordance with federal, local, and institutional guidelines
- •Males and females ≥ 18 years of age
- •Multiple Myeloma
- •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
- •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
- •Life expectancy of more than three months
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
- •Adequate hepatic function, with bilirubin < 2 times the upper limit of normal (ULN) and alanine aminotransferase (ALT) < 3 times ULN
- •Total white blood cell (WBC) count ≥ 2,000/mm³
- •Absolute neutrophil count (ANC) ≥ 1,000/mm³
- •Hemoglobin ≥ 7 gm/dL
- •Subjects may receive red blood cell (RBC) transfusions or supportive care with erythropoietin or darbepoetin in accordance with institutional guidelines
- •Platelet count ≥ 30,000/ mm³
- •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 three months following the last dose if sexually active with a female of child-bearing potential
排除标准
- •Glucocorticoid therapy in a dose equivalent to prednisone ≥ 20 mg/day within 14 days prior to first dose of study drug
- •POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
- •Plasma cell leukemia
- •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
- •Radiation therapy or immunotherapy within 3 weeks prior to first dose; localized radiation therapy within 1 week prior to first dose
- •Participation in an investigational therapeutic study within 14 days prior to first dose of study drug
- •Prior carfilzomib treatment
- •Pregnant or lactating females
- •Major surgery within 3 weeks prior to first dose of study drug
- •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
- •Uncontrolled hypertension
- •Recent history of acute active infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to first dose of study drug
- •Known or suspected human immunodeficiency virus (HIV) infection, known HIV seropositivity
- •Active hepatitis A, B, or C infection
- •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
- •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
- •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
- •Subjects in whom the required program of oral hydration and intravenous fluid hydration is contraindicated, e.g., due to preexisting pulmonary or cardiac impairment
- •Subjects with pleural effusions requiring routine thoracentesis or ascites requiring routine paracentesis
- •Subjects with a known contraindication to receiving dexamethasone or allopurinol
- •Receipt of granulocyte- and granulocyte/ macrophage- colony stimulating factor (G-CSF and GM-CSF) within 1 week prior to first dose of study drug
- •Receipt of pegylated G-CSF within 2 weeks prior to first dose of study drug
- •RBC and platelet transfusions within 7 days prior to first dose of study drug
- •Subjects with known or suspected cardiac amyloidosis
- •Subjects with myelodysplastic syndrome
- •Subjects undergoing peritoneal dialysis
研究组 & 干预措施
Carfilzomib
Experimental
Carfilzomib, 15 mg/m², was administered intravenously (IV) on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.
If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.
干预措施: Carfilzomib (Drug)
结局指标
主要结局
Clearance (CL) of Carfilzomib on Day 1 of Cycle 1
时间窗: Cycle 1, Day 1 before dosing, at the end of the injection, 5, 15, 30, and 60 minutes, and 1.5, 2, 4, 6 and 24 hours postdose.
Plasma concentrations of carfilzomib was determined by a validated liquid chromatography tandem mass spectrometry (LC MS/MS) method. The lower limit of quantitation (LLOQ) was 0.300 ng/mL. Concentration values that were below the LLOQ (BLQ) were set to zero. Pharmacokinetic (PK) parameters were calculated from the individual plasma concentrations of carfilzomib using a noncompartmental method.
次要结局
- Percentage of Carfilzomib Excreted Via Renal Elimination on Day 1 of Cycle 1(Cycle 1, Day 1, 0-5 and 5-24 hours post-dose)
- Plasma Protein Binding (PPB) of Carfilzomib(End of injection and 5 minutes post-dose on Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 15)
- Time to Progression (TTP)(Participants were followed for disease progression for up to 2 years.)
- Area Under the Plasma Curve Extrapolated to Infinity (AUCinf) for Carfilzomib on Day 1 of Cycle 1(Cycle 1, Day 1, before dosing, at the end of the injection, 5, 15, 30, and 60 minutes, and 1.5, 2, 4, 6 and 24 hours postdose.)
- Area Under the Concentration Time Curve to the Last Measurable Concentration (AUClast) for Carfilzomib on Day 15 of Cycle 2(Cycle 2, Day 15 before dosing, at the end of the injection, 5, 15, 30, and 60 minutes, and 1.5, 2, 4, 6 and 24 hours postdose.)
- Maximum Observed Plasma Concentration of Carfilzomib on Day 1 of Cycle 1(Cycle 1, Day 1, before dosing, at the end of the injection, 5, 15, 30, and 60 minutes, and 1.5, 2, 4, 6 and 24 hours postdose.)
- Maximum Observed Plasma Concentration of Carfilzomib on Day 15 of Cycle 2(Cycle 2, Day 15 before dosing, at the end of the injection, 5, 15, 30, and 60 minutes, and 1.5, 2, 4, 6 and 24 hours postdose.)
- Area Under the Plasma Curve Extrapolated to Infinity (AUCinf) for Carfilzomib on Day 15 of Cycle 1(Cycle 1, Day 15 before dosing, at the end of the injection, 5, 15, 30, and 60 minutes, and 1.5, 2, 4, 6 and 24 hours postdose.)
- Percentage of Carfilzomib Excreted Via Renal Elimination on Day 15 of Cycle 1(Cycle 1, Day 15, 0-5 and 5-24 hours post-dose)
- Overall Response Rate (ORR)(From first dose until 30 days after the last dose; median duration of treatment across all groups was 121 days.)
- Area Under the Concentration Time Curve to the Last Measurable Concentration (AUClast) for Carfilzomib on Day 15 of Cycle 1(Cycle 1, Day 15 before dosing, at the end of the injection, 5, 15, 30, and 60 minutes, and 1.5, 2, 4, 6 and 24 hours postdose.)
- Percentage of Carfilzomib Metabolites Excreted Via Renal Elimination on Day 15 of Cycle 1(Cycle 1, Day 15, 0-5 and 5-24 hours post-dose)
- Clearance (CL) of Carfilzomib on Day 15 of Cycle 1(Cycle 1, Day 15 before dosing, at the end of the injection, 5, 15, 30, and 60 minutes, and 1.5, 2, 4, 6 and 24 hours postdose.)
- Clearance (CL) of Carfilzomib on Day 15 of Cycle 2(Cycle 2, Day 15, before dosing, at the end of the injection, 5, 15, 30, and 60 minutes, and 1.5, 2, 4, 6 and 24 hours postdose.)
- Maximum Observed Plasma Concentration of Carfilzomib on Day 15 of Cycle 1(Cycle 1, Day 15 before dosing, at the end of the injection, 5, 15, 30, and 60 minutes, and 1.5, 2, 4, 6 and 24 hours postdose.)
- Area Under the Plasma Curve Extrapolated to Infinity (AUCinf) for Carfilzomib on Day 15 of Cycle 2(Cycle 2, Day 15 before dosing, at the end of the injection, 5, 15, 30, and 60 minutes, and 1.5, 2, 4, 6 and 24 hours postdose.)
- Area Under the Concentration Time Curve to the Last Measurable Concentration (AUClast) for Carfilzomib on Day 1 of Cycle 1(Cycle 1, Day 1 before dosing, at the end of the injection, 5, 15, 30, and 60 minutes, and 1.5, 2, 4, 6 and 24 hours postdose.)
- Percentage of Carfilzomib Metabolites Excreted Via Renal Elimination on Day 1 of Cycle 1(Cycle 1, Day 1, 0-5 and 5-24 hours post-dose)
- Clinical Benefit Rate (CBR)(From first dose until 30 days after the last dose; median duration of treatment across all groups was 121 days.)
- Duration of Response(Participants were followed for disease progression for up to 2 years.)
研究者
研究点 (5)
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