A Phase 2, Prospective, Randomized, Multicenter, Double-blind, Active-control, Parallel-group Study to Determine the Safety of and to Select a Treatment Regimen of CC-4047 (Pomalidomide) Either as Single-agent or in Combination With Prednisone to Study Further in Subjects With Myelofibrosis With Myeloid Metaplasia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Celgene
- 入组人数
- 88
- 试验地点
- 11
- 主要终点
- Percentage of Participants With a Clinical Response Within the First 6 Cycles of Treatment
研究概览
简要总结
The purpose of this study is to determine the safety of and to select a treatment regimen of pomalidomide (CC-4047) either as single-agent or in combination with prednisone to study further in patients with myelofibrosis with myeloid metaplasia (MMM).
详细描述
Participants received study treatment in the Double Blind Treatment Phase for up to 12 cycles (336 days; 12 cycles of 28 days each). Participants who completed the Double-Blind Treatment Phase were unblinded and, if receiving pomalidomide and determined to have a complete remission (CR), partial remission (PR) or clinical improvement (CI) using the International Working Group (IWG) Response Criteria in the study protocol, could have continued on their current dose of pomalidomide until disease progression. Participants receiving placebo were discontinued from the study.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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 sign an informed consent form
- •Must be >18 years of age
- •Must be diagnosed with myelofibrosis
- •Eligibility is based on local pathology review of bone marrow aspirate and biopsy
- •Screening total hemoglobin level < 10g/dL or transfusion-dependent anemia defined as per International Working Group (IWG) criteria.
- •Must have adequate organ function as demonstrated by the following ≤ 14 days prior to starting study drug:
- •Alanine aminotransferase (ALT; SGPT)/aspartate aminotransferase (AST; SGOT) ≤ 3 x upper limit of normal (ULN), [unless upon judgment of the treating physician, it is believed to be due to extra-medullary hematopoiesis (EMH)].
- •Total Bilirubin <3x ULN or Direct Bilirubin <2 x ULN
- •Serum creatinine ≤ 2.0 mg/dL
- •Absolute neutrophil count ≥ 1,000/μL (≥ 1 x 10^9/L).
- •Platelet count ≥ 50,000 /μL (≥ 50 x 10^9/L).
- •Patients must be willing to receive transfusion of blood products
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2 at screening.
- •Must be able to adhere to the study visit schedule and other protocol requirements.
- •No active malignancies with the exception of controlled prostate cancer, basal cell or squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast.
- •Must agree to follow pregnancy precautions as required per the protocol
排除标准
- •Known positive status for human immunodeficiency virus (HIV), hepatitis B carrier, or active hepatitis C infection.
- •Previous untoward reaction to corticosteroid (specifically, prednisone) therapy that was severe enough, in the opinion of the treating physician, to preclude study participation.
- •The use of any growth factors, cytotoxic chemotherapeutic agents (e.g. hydroxyurea and anagrelide), corticosteroids, or experimental drug or therapy within a minimum of 28 days of starting CC-4047 and/or lack of recovery from all toxicity from previous therapy to grade 1 or better (e.g. alpha interferon may require 84 days of longer or washout).
- •Prior therapy with CC-4047 or, lenalidomide or thalidomide for Myelofibrosis with myeloid metaplasia (MMM). (Prior prednisone use as a therapy for MMM is allowed, but not within 28 days of starting CC-4047).
- •History of deep vein thrombosis or pulmonary embolism within one year of starting study medication.
- •Any serious medical condition or psychiatric illness that would prevent, (as judged by the treating physician) the subject from signing the informed consent form or any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
- •Pregnant or lactating females
研究组 & 干预措施
Prednisone
Participants received oral prednisone from Day 1-28 of each 28-day cycle for up to 3 cycles (84 days), 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day, and pomalidomide placebo tablets on Days 1-28 for up to 12 cycles in the Double-Blind Treatment Phase.
After the completion of cycle 12 and upon unblinding, participants were discontinued from the study.
干预措施: Prednisone (Drug)
Prednisone
Participants received oral prednisone from Day 1-28 of each 28-day cycle for up to 3 cycles (84 days), 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day, and pomalidomide placebo tablets on Days 1-28 for up to 12 cycles in the Double-Blind Treatment Phase.
After the completion of cycle 12 and upon unblinding, participants were discontinued from the study.
干预措施: Placebo to pomalidomide (Drug)
Pomalidomide
Participants received 2 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and prednisone placebo tablets on Days 1-28 for the first 3 cycles in the Double-Blind Treatment Phase.
After the completion of Cycle 12 and upon unblinding, participants determined to have a complete remission (CR), partial remission (PR) or clinical improvement (CI) using the International Working Group (IWG) Response Criteria in the study protocol, were eligible to participate in the extension phase and continue to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle, until disease progression, unacceptable toxicity or voluntary withdrawal.
干预措施: Pomalidomide (Drug)
Pomalidomide
Participants received 2 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and prednisone placebo tablets on Days 1-28 for the first 3 cycles in the Double-Blind Treatment Phase.
After the completion of Cycle 12 and upon unblinding, participants determined to have a complete remission (CR), partial remission (PR) or clinical improvement (CI) using the International Working Group (IWG) Response Criteria in the study protocol, were eligible to participate in the extension phase and continue to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle, until disease progression, unacceptable toxicity or voluntary withdrawal.
干预措施: Placebo to prednisone (Drug)
Pomalidomide 2 mg + Prednisone
Participants received 2 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase.
After the completion of cycle 12 and upon unblinding, participants determined to have a complete remission (CR), partial remission (PR) or clinical improvement (CI) using the International Working Group (IWG) Response Criteria in the study protocol, were eligible to participate in the extension phase and continue to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle, until disease progression, unacceptable toxicity or voluntary withdrawal.
干预措施: Pomalidomide (Drug)
Pomalidomide 2 mg + Prednisone
Participants received 2 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase.
After the completion of cycle 12 and upon unblinding, participants determined to have a complete remission (CR), partial remission (PR) or clinical improvement (CI) using the International Working Group (IWG) Response Criteria in the study protocol, were eligible to participate in the extension phase and continue to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle, until disease progression, unacceptable toxicity or voluntary withdrawal.
干预措施: Prednisone (Drug)
Pomalidomide 0.5 mg + Prednisone
Participants received 0.5 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase.
After the completion of cycle 12 and upon unblinding, participants determined to have a complete remission (CR), partial remission (PR) or clinical improvement (CI) using the International Working Group (IWG) Response Criteria in the study protocol, were eligible to participate in the extension phase and continue to receive oral pomalidomide 0.5 mg daily, from Days 1-28 of each cycle, until disease progression, unacceptable toxicity or voluntary withdrawal.
干预措施: Pomalidomide (Drug)
Pomalidomide 0.5 mg + Prednisone
Participants received 0.5 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase.
After the completion of cycle 12 and upon unblinding, participants determined to have a complete remission (CR), partial remission (PR) or clinical improvement (CI) using the International Working Group (IWG) Response Criteria in the study protocol, were eligible to participate in the extension phase and continue to receive oral pomalidomide 0.5 mg daily, from Days 1-28 of each cycle, until disease progression, unacceptable toxicity or voluntary withdrawal.
干预措施: Prednisone (Drug)
结局指标
主要结局
Percentage of Participants With a Clinical Response Within the First 6 Cycles of Treatment
时间窗: Up to 168 days
A clinical responder was defined as either: 1. A baseline red blood cell (RBC)-transfusion-dependent participant with a ≥ 56 consecutive day RBC transfusion-free period after the first dose of study drug, or 2. A baseline RBC-transfusion-independent participant with an increase in hemoglobin of 2.0 g/dL or more from baseline for ≥ 56 consecutive days in the absence of RBC transfusions, or 3. A participant with either a ≥ 50% reduction in palpable splenomegaly of a spleen that was ≥ 10 cm at baseline or a spleen that was palpable at \> 5 cm and became not palpable. Participants who discontinued the study early without achieving clinical response were counted as non-responders.
次要结局
- Percentage of Participants With a Clinical Response Within the First 12 Cycles of Treatment(Up to 336 days)
- Time to the First Clinical Response(Up to 168 days)
- Duration of First Clinical Response(Up to 40 months)
- Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Subscale and Total Scores(Baseline and Cycle 6 (168 days).)
- Change From Baseline in Hemoglobin Concentration for Responders(Baseline, Cycle 6 (168 days))
- Change From Baseline in Hemoglobin Concentration for Non-Responders(Baseline, Cycle 6 (168 days))
- Change From Baseline in Likert Abdominal Pain Scale(Baseline and Cycle 6 (168 days))
- Percentage of Participants With Clinical Response by Baseline JAK2 Assessment(Up to 336 days)
- Number of Participants With Adverse Events (AEs)(From date of the first dose of the study drug until discontinuation or the data cut-off date (up to approximately 45 months).)