A Phase 3, Muticenter, Randomized, Open-label Study to Compare the Efficacy and Safety of Pomalidomide in Combination With Low-dose Dexamethasone Versus High-dose Dexamethasone in Subjects With Refractory or Relapsed and Refractory Multiple Myeloma
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Celgene
- 入组人数
- 455
- 试验地点
- 94
- 主要终点
- Progression-free Survival (PFS) - Primary Analysis
研究概览
简要总结
The purpose of this study is to compare efficacy and safety of pomalidomide in combination with low-dose dexamethasone versus high-dose dexamethasone in subjects with refractory or relapsed and refractory multiple myeloma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Must be ≥ 18 years of age
- •Subjects must have documented diagnosis of multiple myeloma and have measurable disease
- •Subjects must have undergone prior treatment with ≥ 2 treatment lines of anti-myeloma therapy
- •Subjects must have either refractory or relapsed and refractory disease defined as documented disease progression during or within 60 days of completing their last myeloma therapy
- •All subjects must have received at least 2 consecutive cycles of prior treatment that included lenalidomide and bortezomib
- •All subjects must have failed treatment with both lenalidomide and bortezomib in one of the following ways: 1) Documented progressive disease on or within 60 days of completing treatment with lenalidomide and/or bortezomib, or 2) In case of prior response [≥ partial response (PR)] to lenalidomide or bortezomib, subjects must have relapsed within 6 months after stopping treatment with lenalidomide and/or bortezomib-containing regimens, or 3) Subjects who have not had a ≥ minimal response (MR) and have developed intolerance/toxicity after a minimum of two cycles of lenalidomide- and/or bortezomib-containing regimen
- •Patients must have received adequate prior alkylator therapy
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
- •Females of childbearing potential (FCBP) must not become pregnant for 28 days prior to initiation of study drug, during the study, and for 28 days after discontinuation
- •Females must agree to abstain from breastfeeding during study participation and 28 days after study drug discontinuation
- •Males must agree to use a latex condom during any sexual during the study and for 28 days following discontinuation from this study
- •Males must also agree to refrain from donating semen or sperm while on pomalidomide and for 28 days after discontinuation from this study
排除标准
- •Any of the following laboratory abnormalities:
- •Absolute neutrophil count (ANC) < 1,000/μL
- •Platelet count < 75,000/ μL for subjects in whom < 50% of bone marrow nucleated cells are plasma cells
- •Creatinine clearance < 45 mL/min
- •Corrected serum calcium > 14 mg/dL
- •Hemoglobin ≤ 8 g/dL
- •Serum glutamic oxaloacetic transaminase (SGOT)/ aspartate aminotransferase (AST) or transaminase, serum glutamic pyruvic (SGPT)/ alanine aminotransferase (ALT) > 3.0 x upper limit of normal (ULN)
- •Serum total bilirubin > 2.0 mg/dL
- •Previous therapy with pomalidomide
- •Hypersensitivity to thalidomide, lenalidomide, or dexamethasone
- •Resistance to high-dose dexamethasone used in the last line of therapy
- •Peripheral neuropathy ≥ Grade 2
- •Subjects who received an allogeneic bone marrow or allogeneic peripheral blood stem cell transplant
- •Subjects who are planning for or who are eligible for stem cell transplant
- •Subjects with any one of the following: 1) Congestive heart failure, 2) Myocardial infarction within 12 months prior to starting study treatment, 3) 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: 1) Plasmapheresis, 2) Major surgery, 3) Radiation therapy, 4) Use of any anti-myeloma drug therapy
- •Use of any investigational agents within 28 days or 5 half-lives (whichever is longer) of treatment
- •Subjects with conditions requiring chronic steroid or immunosuppressive treatment
- •Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
- •Incidence of gastrointestinal disease that may significantly alter the absorption of pomalidomide
- •Subjects unable or unwilling to undergo antithrombotic prophylactic treatment
- •Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subjects from signing the informed consent form
- •Pregnant or breastfeeding females
- •Known human immunodeficiency virus (HIV) positivity or active infectious hepatitis A, B, or C
研究组 & 干预措施
Pomalidomide + Low-Dose Dexamethasone
Participants received 4 mg pomalidomide administered by mouth on Days 1 to 21 of each 28-day treatment cycle and 40 mg dexamethasone (or 20 mg for participants > 75 years of age) administered by mouth once per day on Days 1, 8, 15, and 22 of each 28-day cycle until disease progression.
干预措施: pomalidomide (Drug)
Pomalidomide + Low-Dose Dexamethasone
Participants received 4 mg pomalidomide administered by mouth on Days 1 to 21 of each 28-day treatment cycle and 40 mg dexamethasone (or 20 mg for participants > 75 years of age) administered by mouth once per day on Days 1, 8, 15, and 22 of each 28-day cycle until disease progression.
干预措施: Dexamethasone (Drug)
High-Dose Dexamethasone
Participants received 40 mg dexamethasone (or 20 mg for participants > 75 years of age) administered by mouth once per day on Days 1 to 4, 9 to 12, and 17 to 20 of each 28-day treatment cycle until disease progression.
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Progression-free Survival (PFS) - Primary Analysis
时间窗: From randomization until the data cut-off date of 07 September 2012. Maximum duration of follow-up for PFS assessments was 57 weeks.
Progression-free survival was calculated as the time from randomization to disease progression as determined by the Independent Response Adjudication Committee based on the International Myeloma Working Group Uniform Response criteria (IMWG), or death on study, whichever occurred earlier. Progressive disease required 1 of the following: • Increase of ≥ 25% from nadir in: o Serum M-component (absolute increase ≥ 0.5 g/dl); o Urine M-component (absolute increase ≥ 200 mg/24 hours); o Bone marrow plasma cell percentage (absolute % ≥ 10%); • Development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas; • Development of hypercalcemia (corrected serum calcium \> 11.5 mg/dl) attributed solely to plasma cell proliferative disease.
Progression-free Survival (PFS) With a Later Cut-off Date
时间窗: From randomization until the data cut-off date of 01 March 2013. Maximum duration of follow-up for PFS assessments was 74 weeks.
Progression-free survival was calculated as the time from randomization to disease progression as determined by the Independent Response Adjudication Committee based on the International Myeloma Working Group Uniform Response criteria (IMWG), or death on study, whichever occurred earlier. Progressive disease requires 1 of the following: • Increase of ≥ 25% from nadir in: o Serum M-component (absolute increase ≥ 0.5 g/dl); o Urine M-component (absolute increase ≥ 200 mg/24 hours); o Bone marrow plasma cell percentage (absolute % ≥ 10%); • Development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas; • Development of hypercalcemia (corrected serum calcium \> 11.5 mg/dl) attributed solely to plasma cell proliferative disease.
次要结局
- Number of Participants With Adverse Events (AEs)(From first dose of study drug through to 30 days after the last dose as of the end of the study (29 August 2017); maximum time on treatment was 297, 269, and 239 weeks in the Pomalidomide + LD-Dex, HD-Dex, and cross-over groups respectively.)
- Overall Survival - Primary Analysis(From randomization until the data cut-off date of 07 September 2012. Maximum time on follow-up for survival was 70 weeks.)
- Percentage of Participants With an Objective Response According to International Myeloma Working Group (IMWG) Uniform Response Criteria(From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.)
- Overall Survival With a Later Cut-off Date(From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up for survival was 93 weeks.)
- Overall Survival Based on the Final Dataset(From randomization until the data cut-off date of 29 August 2017. Maximum time on follow-up for survival was 324 weeks.)
- Percentage of Participants With Objective Response According to European Group for Blood and Marrow Transplantation (EBMT) Criteria(From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.)
- Time to Progression(From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.)
- Time to Response(From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.)
- Duration of Response(From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.)
- Time to the First Hemoglobin Improvement(From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.)
- Time to Improvement in Bone Pain(From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.)
- Time to Improvement in Renal Function(From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.)
- Time to Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status(From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.)
- Change From Baseline in the European Organization for Research and Treatment of Cancer Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Domain(Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6)
- Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain(Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6)
- Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain(Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6)
- Change From Baseline in the EORTC QLQ-C30 Fatigue Domain(Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6)
- Change From Baseline in the EORTC QLQ-C30 Pain Domain(Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6)
- Change From Baseline in the European Organization for Research and Treatment of Cancer QoL Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms(Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6)
- Change From Baseline in the EORTC QLQ-MY20 Side Effects Domain(Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6)
- Change From Baseline in the European Quality of Life-5 Dimensions (EQ-5D) Utility Index Score(Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6)
- Time to First Worsening of Quality of Life (QOL) Domains(Assessed on Day 1 of the first 6 treatment cycles.)