A Phase 2, Open-Label, Multicenter, Dose-Escalation and Expansion Study of Venetoclax in Combination With Pomalidomide and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 8
- 试验地点
- 11
- 主要终点
- Number of Participants With Adverse Events
研究概览
简要总结
This was an open-label, multicenter study designed to evaluate the safety and preliminary efficacy of venetoclax combined with pomalidomide and dexamethasone in participants with relapsed or refractory (R/R) multiple myeloma (MM) who received at least 1 prior line of therapy with documented evidence of progression during or after the participant's last treatment regimen. The study was designed to consist of 2 parts: Part 1 (dose escalation) and Part 2 (dose expansion). For Part 2 the participants were to be divided into 2 cohorts, participants positive for t(11;14) translocation and participants negative for t(11;14) translocation.
详细描述
Following communication of the results of the primary progression-free survival (PFS) analysis from the Phase 3 BELLINI study (Study M14-031; NCT02755597), the company-sponsored MM studies were placed on partial clinical hold (PCH) in March 2019 by the United States (US) Food and Drug Administration and enrollment was halted. The sponsor did not pursue release of the PCH for this study; therefore, enrollment was not re-opened. In accordance with the terms of the PCH, participants who were deriving clinical benefit were allowed to continue to receive treatment. One participant was still active in Part 1 of the study when the sponsor decided not to pursue release of the PCH (in January 2020) and, therefore, continued to receive treatment and have regular assessments until disease progression. The study was discontinued when the last participant completed study treatment. No participants were enrolled in Part 2 of the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Relapsed or refractory (R/R) multiple myeloma (MM) with documented evidence of progression during or after the participant's last treatment regimen
- •Measurable disease as described in the protocol
- •Received at least 1 prior line of therapy as described in the protocol
- •Must meet prior antimyeloma treatment parameters, as described in the protocol, and includes:
- •Received at least 2 consecutive cycles of lenalidomide or a lenalidomide-containing regimen
- •Refractory to lenalidomide
- •Exposed to a proteasome inhibitor (PI) alone or in combination with another agent
- •Had a response of partial response (PR) or better to prior therapy based on the investigator's determination of response as defined by International Myeloma Working Group (IMWG) criteria
- •Has t(11;14) status as described in the protocol and meets the following criteria:
- •For Part 1: MM participants independent of cytogenetic profile
- •For Part 2, Arm A: participant must be t(11;14) positive
- •For Part 2, Arm B: participant must be t(11;14) negative
- •An Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- •Adequate kidney, liver and hematologic laboratory values
排除标准
- •Previous treatment with venetoclax or other BCL-2 inhibitors, or previous treatment with pomalidomide
- •Known sensitivity to any IMiDs
- •Allogenic or syngeneic stem cell transplant within 6 months before the first dose of study drug or active ongoing graft versus host disease
- •Autologous stem cell transplant within 12 weeks before the first dose of study drug
- •Known meningeal involvement of MM
研究组 & 干预措施
Part 1: Dose Escalation
Venetoclax (400 mg oral [PO], once daily [QD]) administered with pomalidomide (4 mg PO, QD) and dexamethasone (40 mg once weekly [qw]) in 28-day cycles until documented disease progression, documented unacceptable toxicity, withdrawal of consent, or the participant met other criteria for discontinuation per study protocol
干预措施: Venetoclax (Drug)
Part 1: Dose Escalation
Venetoclax (400 mg oral [PO], once daily [QD]) administered with pomalidomide (4 mg PO, QD) and dexamethasone (40 mg once weekly [qw]) in 28-day cycles until documented disease progression, documented unacceptable toxicity, withdrawal of consent, or the participant met other criteria for discontinuation per study protocol
干预措施: Pomalidomide (Drug)
Part 1: Dose Escalation
Venetoclax (400 mg oral [PO], once daily [QD]) administered with pomalidomide (4 mg PO, QD) and dexamethasone (40 mg once weekly [qw]) in 28-day cycles until documented disease progression, documented unacceptable toxicity, withdrawal of consent, or the participant met other criteria for discontinuation per study protocol
干预措施: Dexamethasone (Drug)
Part 2: Dose Expansion, t(11;14) positive
Participants positive for t(11;14) translocation were to receive the venetoclax dose determined to be safe in Part 1 as well as pomalidomide (4 mg oral [PO], once daily [QD]) and dexamethasone (40 mg once weekly [qw])
干预措施: Venetoclax (Drug)
Part 2: Dose Expansion, t(11;14) positive
Participants positive for t(11;14) translocation were to receive the venetoclax dose determined to be safe in Part 1 as well as pomalidomide (4 mg oral [PO], once daily [QD]) and dexamethasone (40 mg once weekly [qw])
干预措施: Pomalidomide (Drug)
Part 2: Dose Expansion, t(11;14) positive
Participants positive for t(11;14) translocation were to receive the venetoclax dose determined to be safe in Part 1 as well as pomalidomide (4 mg oral [PO], once daily [QD]) and dexamethasone (40 mg once weekly [qw])
干预措施: Dexamethasone (Drug)
Part 2: Dose Expansion, t(11;14) negative
Participants negative for t(11;14) translocation were to receive the venetoclax dose determined to be safe in Part 1 as well as pomalidomide (4 mg oral [PO], once daily [QD]) and dexamethasone (40 mg once weekly [qw])
干预措施: Venetoclax (Drug)
Part 2: Dose Expansion, t(11;14) negative
Participants negative for t(11;14) translocation were to receive the venetoclax dose determined to be safe in Part 1 as well as pomalidomide (4 mg oral [PO], once daily [QD]) and dexamethasone (40 mg once weekly [qw])
干预措施: Pomalidomide (Drug)
Part 2: Dose Expansion, t(11;14) negative
Participants negative for t(11;14) translocation were to receive the venetoclax dose determined to be safe in Part 1 as well as pomalidomide (4 mg oral [PO], once daily [QD]) and dexamethasone (40 mg once weekly [qw])
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Number of Participants With Adverse Events
时间窗: From first dose of study drug until 30 days following last dose of study drug (up to 70 weeks)
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each event to the use of study drug as either reasonable possibility or no reasonable possibility. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent events (TEAEs/TESAEs) are defined as any event that began or worsened in severity after the first dose of study drug. For more details on adverse events please see the Adverse Event section.
Overall Response Rate (ORR)
时间窗: Approximately 15 months
ORR is defined as the percentage of participants experiencing a stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) using the International Myeloma Working Group (IMWG) 2016 criteria for disease response and progression. CR= negative immunofixation of serum and urine and disappearance of any soft tissue plasmacytomas, and \< 5% plasma cells in bone marrow; sCR= CR + normal serum free light chain (FLC) ratio and absence of clonal cells in bone marrow; VGPR= serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein level + urine M-protein level \< 100 mg per 24 hours; PR= ≥ 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥ 90% or to \< 200 mg per 24 hours.
次要结局
- Time-to-progression (TTP)(Approximately 15 months)
- Progression-Free Survival (PFS)(Approximately 20 months)
- Duration of Response (DOR)(Approximately 15 months)