A Phase 1b/2 Study of Duvelisib and Venetoclax in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or Indolent or Aggressive Non-Hodgkin Lymphoma, Who Have Not Previously Received a Bcl-2 or PI3K Inhibitor
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- 试验地点
- 10
- 主要终点
- Area under the plasma concentration-time curve from time 0 to 24 hours post-dose (AUC24) of venetoclax
研究概览
简要总结
This study is designed to assess the safety, pharmacokinetics, drug-drug interactions, and determine the recommended Phase 2 doses of co administered Duvelisib and Venetoclax in participants with relapsed or refractory chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma, or indolent or aggressive non-Hodgkin lymphoma, who have not previously received a Bcl-2 or Phosphoinositide 3-kinase (PI3K) inhibitor. The Phase 2 portion of the study will preliminarily evaluate efficacy, and expand the toxicity evaluation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject must have either • Relapsed or refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (for Waves 2 or 3)
- •Subject has evaluable disease and requires treatment in the opinion of the investigator.
- •Subject must have relapsed following or be refractory to ≥ 1 standard treatments such as fludarabine based regimens (F, FC, FR, FCR), alkylator (chlorambucil, bendamustine) based regimens, or Bruton's Tyrosine Kinase inhibitor (Ibrutinib).
- •Relapsed or refractory indolent Non-Hodgkin Lymphoma or aggressive Non-Hodgkin Lymphoma (for Waves 1, 2, or 3, unless otherwise indicated)
- •Subject must have histologically documented diagnosis of a Follicular Lymphoma or Marginal Zone Lymphoma.
- •Subject must have histologically documented diagnosis of a Diffuse Large B-cell Lymphoma (excluding Richter's Transformation), Non-cutaneous T-Cell Lymphoma, or Mantle Cell Lymphoma (MCL) (MCL Wave 3 only)
- •Subject has evaluable disease and requires treatment in the opinion of the investigator.
- •Subject must have relapsed following or be refractory to ≥ 1 standard treatments such as R-CHOP, R-CVP, bendamustine, lenalidomide-rituximab, or fludarabine-based regimens.
- •Subject has an Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to
- •Subject must have adequate bone marrow independent of growth factor support per local laboratory reference range at Screening.
- •Subject must have adequate coagulation, renal, and hepatic function, per laboratory reference range at Screening.
- •NHL subjects who have a history of an autologous stem cell transplant (e.g., bone marrow) must be > 6 months post-transplant (prior to the first dose of study drug) and must not require any growth factor support.
排除标准
- •Subject has been previously treated with a Bcl-2 or PI3K inhibitor.
- •Subject is a candidate to receive another second-line therapy approved for usage by the local Health Authority.
- •Subject is appropriate for a stem cell transplant or has undergone an allogeneic stem cell transplant.
- •Subject has received any of the following within 14 days or 5 drug half-lives (whichever is shortest) prior to the first dose of duvelisib or venetoclax, or has not recovered to less than Grade 2 clinically significant adverse effect(s)/toxicity(s) of the previous therapy:
- •Any anti-cancer therapy including chemotherapy or radiotherapy;
- •Investigational therapy, including targeted small molecule agents.
- •Subject has received biologic agents (e.g., monoclonal antibodies) for anti-neoplastic treatment within 30 days prior to first dose of duvelisib or venetoclax.
- •Subject has received live or live attenuated vaccines within 6 weeks prior to first dose of duvelisib or venetoclax.
- •Subject has received the following within 7 days prior to the first dose of duvelisib or venetoclax:
- •Steroid therapy for anti-neoplastic treatment;
- •Strong and Moderate CYP3A inhibitors;
- •Strong and Moderate CYP3A inducers;
- •Chronic immunosuppressants, other than corticosteroids given at daily dose < 20 mg prednisone equivalent for ITP or AIHA.
研究组 & 干预措施
Duvelisib+Venetoclax
干预措施: Duvelisib (Drug)
Duvelisib+Venetoclax
干预措施: Venetoclax (Drug)
结局指标
主要结局
Area under the plasma concentration-time curve from time 0 to 24 hours post-dose (AUC24) of venetoclax
时间窗: Blood samples will be taken at 0 (pre-dose) 1,2,4,6,8,10,12 and 24 hours post-dose on Cycle 1 Days 7 and 14, and Day 22 for second and third dose levels.
The area under the plasma concentration-time curve over a 24-hour dose interval
Recommended phase two dose (RPTD) of Duvelisib in combination with venetoclax
时间窗: Minimum first cycle of dosing (28 days)
Time to maximum observed plasma concentration (Tmax) of duvelisib
时间窗: Blood samples will be taken at 0 (pre-dose) 1,2,4,6,8,10 and 12 hours post-dose on Cycle 1 Day 14 and Day 22 for second and third dose levels.
The time at which the maximum plasma concentration (Cmax) is observed.
Recommended phase two dose (RPTD) of Venetoclax in combination with duvelisib
时间窗: Minimum first cycle of dosing (28 days)
Number of participants with adverse events
时间窗: From participant's first dose until 30 days after participant's last dose of study drug; up to 2 years following last participant first dose
Participants will be monitored for clinical and laboratory evidence of adverse events throughout the study.
Maximum observed plasma concentration (Cmax) of venetoclax
时间窗: Blood samples will be taken at 0 (pre-dose) 1,2,4,6,8,10, 12 and 24 hours post-dose on Cycle 1 Days 7 and 14, and Day 22 for second and third dose levels.
The highest concentration that a drug achieves in the blood after administration in a dosing interval.
Time to maximum observed plasma concentration (Tmax) of venetoclax
时间窗: Blood samples will be taken at 0 (pre-dose) 1,2,4,6,8,10,12 and 24 hours post-dose on Cycle 1 Days 7 and 14, and Day 22 for second and third dose levels.
The time at which the maximum plasma concentration (Cmax) is observed.
Maximum observed plasma concentration (Cmax) of duvelisib
时间窗: Blood samples will be taken at 0 (pre-dose) 1,2,4,6,8,10 and 12 hours post-dose on Cycle 1 Day 14 and Day 22 for second and third dose levels.
The highest concentration that a drug achieves in the blood after administration in a dosing interval.
Area under the plasma concentration-time curve from time 0 to 12 hours post-dose (AUC12) of duvelisib
时间窗: Blood samples will be taken at 0 (pre-dose) 1,2,4,6,8,10 and 12 hours post-dose on Cycle 1 Day 14 and Day 22 for second and third dose levels.
The area under the plasma concentration-time curve over a 12-hour dose interval
次要结局
- Overall Response Rate (ORR)(Measured up to 2 years after the last participant has enrolled in the study)
- Time to Tumor Progression (TTP)(Measured up to 2 years after the last participant has enrolled in the study)
- Duration of Response (DOR)(Measured up to 2 years after the last participant has enrolled in the study)
- Progression-free survival (PFS)(Measured up to 2 years after the last participant has enrolled in the study)