Ibrutinib and Lenalidomide With Dose Adjusted EPOCH-R in Subjects With Relapsed/Refractory Diffuse Large B-cell Lymphoma
A Multicenter Study of Ibrutinib and Lenalidomide in Combination With DA-EPOCH-R in Subjects With Relapsed or Refractory Diffuse Large B-cell Lymphoma
研究概览
地位
干预/治疗
详细说明
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).
研究类型
注册 (实际的)
阶段
- 阶段2
- 阶段1
联系人和位置
学习地点
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California
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Duarte、California、美国、91010
- SITE-1
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Los Angeles、California、美国、90095
- SITE-2
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Orange、California、美国、92868
- SITE-10
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Illinois
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Chicago、Illinois、美国、60612
- SITE-3
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Maryland
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Baltimore、Maryland、美国、21201
- SITE-5
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Bethesda、Maryland、美国、20892
- SITE-6
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Michigan
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Ann Arbor、Michigan、美国、48109
- SITE-4
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New Mexico
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Albuquerque、New Mexico、美国、87106
- SITE-8
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New York
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Stony Brook、New York、美国、11794
- SITE-9
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South Carolina
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Charleston、South Carolina、美国、29425
- SITE-7
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Major inclusion criteria:
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤2
- Pathologically confirmed relapsed/refractory DLBCL
- Subjects must have ≥1 measurable disease site on CT scan (≥ 1.5 cm in longest dimension).
Adequate hepatic and renal function:
- AST or ALT ≤2.5 x ULN
- Serum Creatinine ≤ 2.0 mg/dL and creatinine clearance ≥60 mL/min/1.73
- Bilirubin ≤1.5 x ULN
Adequate hematologic function:
- ANC >1,000 cells/mm3
- Platelets ≥75,000 cells/mm3
- Hemoglobin ≥8.0 g/dL
- Prothrombin time (PT) and activated partial thromboplastin time (aPTT) must be ≤1.5 x the upper limit of the normal range (ULN)
- Must be registered into the Revlimid REMS™program and be willing to comply with the requirements of Revlimid REMS™.
Major Exclusion Criteria:
- 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
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:非随机化
- 介入模型:顺序分配
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的:Part 1: Dose Level 1
Ibrutinib 560 mg PO + DA-EPOCH-R
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依鲁替尼
Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim
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实验性的:Part 1: Dose Level 2
Ibrutinib 560 mg (PO) +lenalidomide 15 mg (PO) + DA-EPOCH-R
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依鲁替尼
Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim
来那度胺
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实验性的:Part 1: Dose Level 3
Ibrutinib 560 mg (PO) +lenalidomide 20 mg (PO) + DA-EPOCH-R
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依鲁替尼
Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim
来那度胺
|
实验性的:Part 1: Dose Level 4
Ibrutinib 560 mg (PO) +lenalidomide 25 mg (PO) + DA-EPOCH-R
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依鲁替尼
Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim
来那度胺
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实验性的:Part 2: RP2D
Recommended Phase 2 Dose(RP2D): Ibrutinib 560 mg (PO) +lenalidomide 25 mg (PO) + DA-EPOCH-R
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依鲁替尼
Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim
来那度胺
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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Number of Participants With Dose-Limiting Toxicities as a Measure of Safety and Tolerability
大体时间:1 year after last subjects received the first dose
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Part-1: To determine the maximum tolerated dose (MTD) of the combination of ibrutinib and lenalidomide with dose adjusted EPOCH-R
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1 year after last subjects received the first dose
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Number of Participants With Complete Responses (CR) and Partial Responses (PR) as a Measure of Efficacy-ORR
大体时间:1 year after last subjects received the first dose
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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.
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1 year after last subjects received the first dose
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Number of Participants With Complete Responses (CR) and Partial Responses (PR) as a Measure of Efficacy
大体时间:1 year after last subjects received the first dose
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Part-1: Overall Response rate (ORR) will defined as the proportion of subjects who achieve either a CR or a PR according to the international Working Group Response Criteria for NHL as assessed by investigator.
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1 year after last subjects received the first dose
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Number of Subjects With Adverse Events as a Measure of Safety and Tolerability
大体时间:1 year after last subjects received the first dose
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Part 2: The frequency (number and percentage) of treatment-emergent adverse events will be reported.
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1 year after last subjects received the first dose
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Progression Free Survival (PFS) and Overall Survival (OS) as a Measure of Efficacy
大体时间: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.
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Part 2: PFS will be measured as time from first study drug administration to disease progression or death from any cause.
OS will be measured from the time of first study drug administration until the date of death using Kaplan-Meier methodology.
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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.
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Duration of Response (DOR)
大体时间: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.
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Part 2: DOR will be measured from the time by which the measurement criteria are met for CR or PR until the first date by which recurrent or progressive disease is objectively documented.
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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.
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合作者和调查者
调查人员
- 研究主任:Jutta Neuenburg, MD、Pharmacyclics LLC (An AbbVie Company)
出版物和有用的链接
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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