Phase 1/2 Open-label Study Of The Safety And Efficacy Of Pd 0332991 In Combination With Bortezomib And Dexamethasone In Patients With Refractory Multiple Myeloma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 53
- 试验地点
- 18
- 主要终点
- Maximum Tolerated Dose (MTD) of PD-0332991: Phase 1
研究概览
简要总结
This is a Phase 1/2 study evaluating the safety and anti-tumor activity of PD 0332991 in combination with Velcade® [bortezomib] and dexamethasone in patients who have received at least one previous treatment for multiple myeloma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Diagnosis of symptomatic multiple myeloma as defined by International Myeloma Working Group (IMWGURC).
- •Phase 1: Relapsed or relapsed/refractory myeloma after at least 1 previous treatments and with a life expectancy of more than 3 months.
- •Phase 2: Measurable (as defined by IMWGURC) disease after at least 1 previous treatment.
排除标准
- •History of allogeneic stem cell transplant.
- •Phase 2 only: Prior bortezomib therapy will only be allowed if there was a demonstrated positive response, and disease progression occurred off therapy.
- •Must have not experienced significant blood level changes, e.g. very low platelets, while on previous bortezomib therapy
- •Prior radiation therapy to > 25% of the bone marrow (whole pelvis is 25%).
研究组 & 干预措施
1
干预措施: Bortezomib (Drug)
1
干预措施: Dexamethasone (Drug)
1
干预措施: PD 0332991 (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of PD-0332991: Phase 1
时间窗: Day 1 up to Day 28 during Cycle 1 in schedule A, Day 1 up to Day 21 during Cycle 1 in schedule B
MTD=highest dose level for which no more than 1 out of 6 participants experienced dose-limiting toxicity (DLT). DLT=any of the following treatment-related events: Absolute neutrophil count (ANC) less than (\<)1000/microliter (mcL) (Grade 3 neutropenia) associated with documented infection/fever \>=38.5degrees Celsius (C); Grade \>=3 nonhematologic treatment-related toxicity, except those that were not maximally treated or considered tolerable, Grade 3 corrected QT interval (QTc) prolongation (QTc \>500 millisecond \[msec\]) in asymptomatic participants even after repeat testing to exclude confounding factors and correction of reversible causes; Delay in the administration of Cycle 2 for more than 1 week of the planned date due to platelet count \<25,000/mcL and/or ANC \<500/mcL, or due to prolonged nonhematologic toxicities of Grade \>=3; Inability to deliver at least 80 percent (%) of the planned PD 0332991 or bortezomib doses during Cycle 1 due to toxicity.
Recommended Phase II Dose (RP2D) of PD-0332991: Phase 1
时间窗: Day 1 up to Day 28 during Cycle 1 in schedule A, Day 1 up to Day 21 during Cycle 1 in schedule B
RP2D was determined based on the MTD, safety and tolerability profile of the study treatment.
Percentage of Participants With Objective Response (OR): Phase 2
时间窗: Cycle 1 Day 1 (baseline) up to end of study (up to cycle 22 for schedule B)
OR: confirmed stringent complete response(sCR),complete response(CR),very good partial response(VGPR) or partial response(PR) as per International Myeloma Working Group Uniform Response Criteria (IMWGURC). sCR: normal serum free light chain (FLC) ratio, absence of clonal cells in bone marrow. CR: disappearance of any soft tissue plasmacytomas, \<5 percent (%) plasma cells in bone marrow, negative immunofixation on serum, urine. VGPR: serum, urine M-protein detectable by immunofixation but not on electrophoresis, \>= 90% reduction in serum M-protein, \<100 mg/24 hour (hr) urine M-protein. PR: \>=50% reduction in serum M-protein, reduction in 24-hr urinary M-protein by \>=90% or to \<200 mg/24 hr, \>=50% decrease in difference between involved and uninvolved FLC levels if serum, urine M-protein were unmeasurable, \>= 50% reduction in plasma cells, provided baseline bone marrow plasma cell was \>=30% if serum, urine M-protein were unmeasurable and serum free light assay was unmeasureable.
次要结局
- European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC QLQ-C30): Phase 2(C1D1 (baseline), C1D8, C1D15, C2D1, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1, C10D1, C11D1, C12D1, C13D1, C14D1, C15D1, C16D1, C17D1, C18D1, C19D1, C20D1, C21D1, C22D1, End of Treatment (assessment at early withdrawal occurring up to Cycle 22))
- Progression-free Survival (PFS): Phase 2(Cycle 1 Day 1 (baseline) up to 28 days after last dose of palbociclib)
- Duration of Objective Response (DR): Phase 2(Cycle 1 Day 1 (baseline) up to 28 days after last dose of palbociclib)
- Time to Tumor Progression (TTP): Phase 2(Cycle 1 Day 1 (baseline) up to 28 days after last dose of palbociclib)
- Quality of Life Questionnaire Multiple Myeloma Module (QLQ-MY20): Phase 2(C1D1 (baseline), C1D8, C1D15, C2D1, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1, C10D1, C11D1, C12D1, C13D1, C14D1, C15D1, C16D1, C17D1, C18D1, C19D1, C20D1, C21D1, C22D1, End of Treatment (assessment at early withdrawal occurring up to Cycle 22))
- Percent Change From Screening in Phosphorylated Retinoblastoma (Rb), Tumor Biomarkers and Soluble Biomarkers Levels: Phase 1(Screening, C1D1(baseline), C1D8, C1D15, C2D1, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1, C10D1, C11D1, C12D1, C13D1, C14D1, C15D1, C16D1, C17D1, C18D1, C19D1, C20D1, C21D1, C22D1, End of Treatment (assessment at early withdrawal occurring up to Cycle 22))
- Best Overall Response: Phase 1(Cycle 1 Day 1 (baseline), assessed on Day 1 of every cycle up to end of study (up to Cycle 22 for schedule A and schedule B))
- Number of Participants With Adverse Events (AEs) by Severity: Phase 2(Cycle 1 Day 1 (baseline) up to 28 days after last dose of palbociclib)
- Number of Participants With Laboratory Abnormalities: Phase 2(Cycle 1 Day 1 (baseline) up to 28 days after last dose of palbociclib)
- Overall Survival (OS): Phase 2(Cycle 1 Day 1 (baseline) up to end of study (up to Cycle 22 for schedule B), thereafter every 3 months until 1 year after the last dose of palbociclib)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Relationship to Study Medication: Phase 2(Cycle 1 Day 1 (baseline) up to 28 days after last dose of palbociclib)
- Modified Version of Brief Pain Inventory - Short Form (m-BPI-sf) Questionnaire: Phase 2(C1D1 (baseline), C1D8, C1D15, C2D1, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1, C10D1, C11D1, C12D1, C13D1, C14D1, C15D1, C16D1, C17D1, C18D1, C19D1, C20D1, C21D1, C22D1, End of Treatment (assessment at early withdrawal occurring up to Cycle 22))