A Phase 1 Multi-Center, Open-Label, Dose-Escalation Study to Determine the Pharmacokinetics and Safety of Pomalidomide When Given in Combination With Low Dose Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma and Impaired Renal Function
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Celgene
- 入组人数
- 25
- 试验地点
- 9
- 主要终点
- PK-Renal clearance (CLr)
研究概览
简要总结
The purpose of this study is to determine the pharmacokinetics (PK) and safety for the combination of pomalidomide (POM) + low-dose dexamethasone (LD- DEX) in subjects with relapsed or refractory Multiple Myeloma (RRMM) and impaired renal function.
详细描述
The primary objective of the study is to determine the PK and safety for the combination of POM + (LD-DEX) in subjects with RRMM and impaired renal function.
The secondary objective of the study is to evaluate the efficacy of POM + (LD_DEX) in subjects with RRMM and impaired renal function.
This is a 3+3 dose escalation design, with one cohort each for patients with severely impaired renal function patients (CrCl < 30 mL/min) requiring and not requiring dialysis respectively. There will also be one control cohort with normal renal function, these patients will receive 4 mg POM. Dosing will be 21 days out of a 28 day cycle.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Factorial
- 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
- •Subjects must satisfy the following criteria to be enrolled in the study:
- •Must be ≥ 18 years at the time of signing the informed consent form
- •Must understand and voluntarily sign an informed consent document prior to any study-related assessments/procedures
- •Must be able to adhere to the study visit schedule and other protocol requirements
- •Must have documented diagnosis of relapsed or refractory multiple myeloma and have measurable disease (serum M-protein ≥ 0.5 g/dL or urine M-protein ≥ 200 mg/24 hours)
- •Must have had at least 1 prior anti-myeloma regimen
- •Must have documented progression as per the International Myeloma Working Group uniform response criteria (Durie, 2006) during or after the last anti-myeloma regimen
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
- •Females of childbearing potential (FCBP) must agree to utilize two reliable forms of contraception simultaneously or practice complete abstinence from heterosexual contact for at least 28 days before starting study drug, while participating in the study (including dose interruptions), and for at least 28 days after study treatment discontinuation, and must agree to regular pregnancy testing during this timeframe
- •Females must agree to abstain from breastfeeding during study participation and for 28 following discontinuation from study treatment
- •Males must agree to use a latex condom during any sexual contact with FCBP while participating in the study and for 28 days following discontinuation from study treatment, even if he has undergone a successful vasectomy
- •Males must also agree to refrain from donating semen or sperm while on pomalidomide and for 28 days after discontinuation from study treatment
- •All subjects must agree to refrain from donating blood while on study drug and for 28 days after discontinuation from study treatment
- •All subjects must agree not to share medication
排除标准
- •The presence of any of the following will exclude a subject from enrollment:
- •Peripheral neuropathy ≥ Grade 2
- •Non-secretory multiple myeloma
- •Any of the following laboratory abnormalities:
- •Absolute neutrophil count (ANC) < 1,000/µL
- •Platelet count < 75,000/µL
- •Corrected serum calcium > 14 mg/dL (> 3.5 mmol/L)
- •Hemoglobin < 8 g/dL (< 4.9 mmol/L; prior RBC transfusion or recombinant human erythropoietin use is permitted)
- •Serum glutamic oxaloacetic transaminase/aspartate aminotransferase (SGOT/AST) or serum glutamic pyruvic transaminase/alanine aminotransferase (SGPT/ALT) > 3.0 x upper limit of normal (ULN)
- •Serum total bilirubin > 2.0 mg/dL
- •Prior history of malignancies, other than the disease being studied, unless the subject has been free of the malignancy for ≥ 5 years from initiating study treatment, with the following exceptions:
- •Basal cell carcinoma of the skin
- •Squamous cell carcinoma of the skin
- •Carcinoma in situ of the cervix
- •Carcinoma in situ of the breast
- •Incidental histologic finding of prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinical staging system).
- •Previous therapy with Pomalidomide
- •Hypersensitivity to thalidomide, lenalidomide, or dexamethasone
- •Rash ≥ Grade 3 during prior thalidomide or lenalidomide therapy
- •Incidence of gastrointestinal disease that may significantly alter the absorption of pomalidomide
- •Subjects with any one of the following:
- •Congestive heart failure (New York Heart Association Class III or IV)
- •Myocardial infarction within 12 months prior to starting study treatment
- •Unstable or poorly controlled angina pectoris, including Prinzmetal variant angina pectoris
- •Subjects who received any of the following within the last 14 days of initiation of study treatment:
- •Plasmapheresis
- •Major surgery (kyphoplasty is not considered major surgery)
- •Radiation therapy (with the exception of radiation therapy to a pathological fracture site to enhance bone healing or to treat post-fracture pain that is refractory to narcotic analgesics)
- •Any anti-myeloma drug therapy
- •Use of any investigational agents within 28 days or 5 half-lives (whichever is longer) of initiating study treatment
- •Subjects with conditions requiring chronic steroid or immunosuppressive treatment, such as rheumatoid arthritis, multiple sclerosis, and lupus, which likely need additional steroid or immunosuppressive treatments in addition to the study treatment. Includes subjects receiving corticosteroids (> 10 mg/day of prednisone or equivalent) within 3 weeks prior to initiating study treatment
- •Subjects unable or unwilling to undergo antithrombotic prophylactic treatment will not be eligible to participate in this study
- •Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
- •Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subjects from signing the informed consent form
- •Pregnant or breastfeeding females
研究组 & 干预措施
4 mg Oral POM + 40 mg Oral DEX
Oral POM at 4 mg on days 1-21 of a 28-day cycle, Oral DEX at 40 mg/day (≤ 75 years old) or 20 mg/day (> 75 years old) on days 1, 8, 15 and 22 of a 28-day cycle
干预措施: 4 mg Oral POM + 40 mg Oral DEX (Drug)
2 mg Oral POM + 40 mg Oral DEX
Oral POM at 2 mg on days 1-21 of a 28-day cycle, Oral DEX at 40 mg/day (≤ 75 years old) or 20 mg/day (> 75 years old) on days 1, 8, 15 and 22 of a 28-day cycle
干预措施: 2 mg Oral POM + 40 mg Oral DEX (Drug)
结局指标
主要结局
PK-Renal clearance (CLr)
时间窗: 24 times over 7 months
PK-Renal clearance (CLr)
PK-Effective terminal half-life (T1/2)
时间窗: 24 times over 7 months
PK-Effective terminal half-life (T1/2)
PK-Area under the plasma concentration time curve (AUC)
时间窗: Up to 24 times over 7 months
PK-Area under the plasma concentration time curve (AUC)
PK-Apparent total body clearance (CL/F)
时间窗: 24 times up to 7 months
PK-Apparent total body clearance (CL/F)
PK-Time to maximum plasma concentration (Cmax)
时间窗: 24 times over 7 months
PK-Time to maximum plasma concentration (Cmax)
PK-Apparent volume of distribution (V/F)
时间窗: 24 times over 7 months
PK-Apparent volume of distribution (V/F)
次要结局
- Duration of response(Up to 5 years)
- Number of participants alive(Up to 5 years)
- Number of participants with adverse events (AEs)(Up to 5 years)
- Time to response(Up to 5 years)