A Multicenter Study of Ibrutinib and Lenalidomide in Combination With DA-EPOCH-R in Subjects With Relapsed or Refractory Diffuse Large B-cell Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 35
- 试验地点
- 10
- 主要终点
- Number of Participants With Dose-Limiting Toxicities as a Measure of Safety and Tolerability
研究概览
简要总结
This is a Phase 1b/2, open-label, non-randomized multicenter study to assess the safety and efficacy of ibrutinib and lenalidomide in combination with DA-EPOCH-R in subjects with relapsed/refractory Diffuse Large B-cell Lymphoma (DLBCL).
详细描述
This is a Phase 1b, open-label, non-randomized multicenter study conducted in 2 parts. Part 1, will determine the MTD of the combination of ibrutinib, lenalidomide and DA-EPOCH-R in subjects with DLBCL.
Ibrutinib will be administered at a fixed dose of 560 mg and lenalidomide will be dose-escalated. DA-EPOCH-R will be given at standard doses.
For Part 2, the MTD determined in Part 1 will be the dose used for all subjects. If no MTD is identified, then subjects in Part 2 will be treated with the maximum administered doses (MAD, treatment doses from dose Level 4).
The primary objective for Part 2 is to determine the ORR of ibrutinib and lenalidomide in combination with DA-EPOCH-R in subjects with ABC DLBCL as analyzed by gene expression profiling when treated at recommended phase 2 dose (RP2D).
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
- 未提供
排除标准
- •Known central nervous system lymphoma
- •Any chemotherapy, external beam radiation therapy, or anti-cancer antibodies within 2 weeks
- •Radio- or toxin-immunoconjugates within 10 weeks
- •Prior allogenetic stem cell (or other organ) transplant within 6 months or any evidence of active graft-versus-host disease or requirement for immunosuppressants within 28 days prior to first dose of study drug
研究组 & 干预措施
Part 2: RP2D
Recommended Phase 2 Dose(RP2D): Ibrutinib 560 mg (PO) +lenalidomide 25 mg (PO) + DA-EPOCH-R
干预措施: Lenalidomide (Drug)
Part 1: Dose Level 1
Ibrutinib 560 mg PO + DA-EPOCH-R
干预措施: Ibrutinib (Drug)
Part 1: Dose Level 1
Ibrutinib 560 mg PO + DA-EPOCH-R
干预措施: DA-EPOCH-R (Drug)
Part 1: Dose Level 2
Ibrutinib 560 mg (PO) +lenalidomide 15 mg (PO) + DA-EPOCH-R
干预措施: Ibrutinib (Drug)
Part 1: Dose Level 2
Ibrutinib 560 mg (PO) +lenalidomide 15 mg (PO) + DA-EPOCH-R
干预措施: DA-EPOCH-R (Drug)
Part 1: Dose Level 2
Ibrutinib 560 mg (PO) +lenalidomide 15 mg (PO) + DA-EPOCH-R
干预措施: Lenalidomide (Drug)
Part 1: Dose Level 3
Ibrutinib 560 mg (PO) +lenalidomide 20 mg (PO) + DA-EPOCH-R
干预措施: Ibrutinib (Drug)
Part 1: Dose Level 3
Ibrutinib 560 mg (PO) +lenalidomide 20 mg (PO) + DA-EPOCH-R
干预措施: DA-EPOCH-R (Drug)
Part 1: Dose Level 3
Ibrutinib 560 mg (PO) +lenalidomide 20 mg (PO) + DA-EPOCH-R
干预措施: Lenalidomide (Drug)
Part 1: Dose Level 4
Ibrutinib 560 mg (PO) +lenalidomide 25 mg (PO) + DA-EPOCH-R
干预措施: Ibrutinib (Drug)
Part 1: Dose Level 4
Ibrutinib 560 mg (PO) +lenalidomide 25 mg (PO) + DA-EPOCH-R
干预措施: DA-EPOCH-R (Drug)
Part 1: Dose Level 4
Ibrutinib 560 mg (PO) +lenalidomide 25 mg (PO) + DA-EPOCH-R
干预措施: Lenalidomide (Drug)
Part 2: RP2D
Recommended Phase 2 Dose(RP2D): Ibrutinib 560 mg (PO) +lenalidomide 25 mg (PO) + DA-EPOCH-R
干预措施: Ibrutinib (Drug)
Part 2: RP2D
Recommended Phase 2 Dose(RP2D): Ibrutinib 560 mg (PO) +lenalidomide 25 mg (PO) + DA-EPOCH-R
干预措施: DA-EPOCH-R (Drug)
结局指标
主要结局
Number of Participants With Dose-Limiting Toxicities as a Measure of Safety and Tolerability
时间窗: 1 year after last subjects received the first dose
Part-1: To determine the maximum tolerated dose (MTD) of the combination of ibrutinib and lenalidomide with dose adjusted EPOCH-R
Number of Participants With Complete Responses (CR) and Partial Responses (PR) as a Measure of Efficacy-ORR
时间窗: 1 year after last subjects received the first dose
Part 2 - Overall Response rate will be defined as the proportion of subjects who achieve either a Complete Response or a Partial Response according to the international Working Group Response Criteria for NHL as assessed by investigator.
次要结局
- Number of Subjects With Adverse Events as a Measure of Safety and Tolerability(1 year after last subjects received the first dose)
- Duration of Response (DOR)(From initial response date until the date of first documented progression or death from any cause, whichever came first, assessed up to approximately 1 year after the last subject received the first dose.)
- Progression Free Survival (PFS) and Overall Survival (OS) as a Measure of Efficacy(From initial dose date until the date of first documented progression or death from any cause, whichever came first, assessed up to approximately 1 year after the last subject received the first dose, up to 36 months at the most.)
- Number of Participants With Complete Responses (CR) and Partial Responses (PR) as a Measure of Efficacy(1 year after last subjects received the first dose)