A Phase 1b Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of the Combination of Duvortuxizumab With Ibrutinib in Subjects With B-Cell Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 主要终点
- Part 1: Number of Participants With Dose Limiting Toxicity
研究概览
简要总结
The purpose of this study is to determine whether duvortuxizumab and ibrutinib can be combined safely and to establish the maximum tolerated dose (MTD) in Part 1 and the recommended Phase 2 dose (RP2D) and to further explore the safety of duvortuxizumab in combination with ibrutinib at the RP2D in participants with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and chronic lymphocytic leukemia (CLL) in Part 2.
详细描述
This is an open-label (identity of study drug will be known to participant and study staff), multicenter (when more than one hospital or medical school team work on a medical research study), Phase 1b study. The purpose of this study is to see if duvortuxizumab in combination with ibrutinib is safe and useful for treating participants with B-cell malignancies. This study will be conducted in 2 parts: Part 1: Dose Optimization and Part 2: Dose Expansion. Part 1 will determine what dose of duvortuxizumab can be given safely with the standard dose of ibrutinib to participants with previously treated B-cell malignancies. Part 2 will look at how previously treated DLBCL, FL, MCL, and CLL participants respond to a safe dose of duvortuxizumab in combination with ibrutinib. Part 2 will also test whether the dose from Part 1 is an effective cancer therapy. The study consists of a Screening Phase, an ibrutinib Run-In Phase (Part 2 only), a combination (duvortuxizumab plus ibrutinib) Treatment Phase (Day 1, Cycle 1 and continues until the completion of the End-of-Treatment Visit), End-of-Treatment Visit (30 days (+7 days) after the last dose of study drug), and Post-treatment Follow-up Phase. The end of the study will be defined as 12 months after the last participant has received the first dose of study treatment. Participants' safety will be monitored throughout the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •The participant has a B-cell malignancy (diffuse large B-cell lymphoma [DLBCL], follicular lymphoma [FL], mantle cell lymphoma [MCL], or chronic lymphocytic leukemia [CLL]) with tumor progression following at least one (MCL and CLL) or two (DLBCL and FL) prior standard therapies
- •The participant has a radiographically measurable tumor that requires treatment according to the treating physician
- •The participant is able to carry out daily life activities with significant difficulty
- •The participant has adequate organ and blood cell counts
- •Sexually active participants must use medically acceptable methods of contraception during the course of the study
排除标准
- •The participant has a brain tumor or significant side effects, including severe neurological side effects, from a previous anti-cancer treatment
- •Current severe, uncontrolled systemic disease including an ongoing, active infection or history of clinically significant heart problems
- •History of autoimmune disease, allogeneic hematopoietic stem cell transplant, or organ transplant
- •The participant has received any of the following: ibrutinib or other Bruton's tyrosine kinase (BTK) inhibitor at any time; an agent targeting CD19-positive cells or CD3-expressing T cells at any time; or warfarin, a vitamin K antagonist, or a blood transfusion (red blood cells and/or platelets) within 1 week of starting the study
- •The participant is pregnant, breastfeeding, or planning to become pregnant or father a child
研究组 & 干预措施
Dose Optimization:Participant with Certain B-Cell Malignancies
Participants with certain B-cell malignancies (diffuse large B-cell lymphoma [DLBCL], mantle cell lymphoma [MCL], or follicular lymphoma [FL]) will receive rising doses of intravenous infusions of duvortuxizumab either with or without a priming dose in combination with oral ibrutinib until disease progression, unacceptable toxicity, or other protocol-specified withdrawal criteria are met. Dose escalation will continue until the recommended phase 2 dose or maximum tolerated dose is reached.
干预措施: Duvortuxizumab (Drug)
Dose Optimization:Participant with Certain B-Cell Malignancies
Participants with certain B-cell malignancies (diffuse large B-cell lymphoma [DLBCL], mantle cell lymphoma [MCL], or follicular lymphoma [FL]) will receive rising doses of intravenous infusions of duvortuxizumab either with or without a priming dose in combination with oral ibrutinib until disease progression, unacceptable toxicity, or other protocol-specified withdrawal criteria are met. Dose escalation will continue until the recommended phase 2 dose or maximum tolerated dose is reached.
干预措施: Ibrutinib (Drug)
Dose Expansion: Participants with DLBCL
Participants with DLBCL will receive intravenous infusions of duvortuxizumab either with or without a priming dose in combination with oral ibrutinib at the recommended phase 2 dose until disease progression, unacceptable toxicity, or other protocol-specified withdrawal criteria are met.
干预措施: Duvortuxizumab (Drug)
Dose Expansion: Participants with DLBCL
Participants with DLBCL will receive intravenous infusions of duvortuxizumab either with or without a priming dose in combination with oral ibrutinib at the recommended phase 2 dose until disease progression, unacceptable toxicity, or other protocol-specified withdrawal criteria are met.
干预措施: Ibrutinib (Drug)
Dose Expansion: Participants with FL
Participants with FL will receive intravenous infusions of duvortuxizumab either with or without a priming dose in combination with oral ibrutinib at the recommended phase 2 dose until disease progression, unacceptable toxicity, or other protocol-specified withdrawal criteria are met.
干预措施: Duvortuxizumab (Drug)
Dose Expansion: Participants with FL
Participants with FL will receive intravenous infusions of duvortuxizumab either with or without a priming dose in combination with oral ibrutinib at the recommended phase 2 dose until disease progression, unacceptable toxicity, or other protocol-specified withdrawal criteria are met.
干预措施: Ibrutinib (Drug)
Dose Expansion: Participants with MCL
Participants with MCL will receive intravenous infusions of duvortuxizumab either with or without a priming dose in combination with oral ibrutinib at the recommended phase 2 dose until disease progression, unacceptable toxicity, or other protocol-specified withdrawal criteria are met.
干预措施: Duvortuxizumab (Drug)
Dose Expansion: Participants with MCL
Participants with MCL will receive intravenous infusions of duvortuxizumab either with or without a priming dose in combination with oral ibrutinib at the recommended phase 2 dose until disease progression, unacceptable toxicity, or other protocol-specified withdrawal criteria are met.
干预措施: Ibrutinib (Drug)
Dose Expansion: Participants with CLL
Participants with chronic lymphocytic leukemia (CLL) will receive intravenous infusions of duvortuxizumab either with or without a priming dose in combination with oral ibrutinib at the recommended phase 2 dose until disease progression, unacceptable toxicity, or other protocol-specified withdrawal criteria are met.
干预措施: Duvortuxizumab (Drug)
Dose Expansion: Participants with CLL
Participants with chronic lymphocytic leukemia (CLL) will receive intravenous infusions of duvortuxizumab either with or without a priming dose in combination with oral ibrutinib at the recommended phase 2 dose until disease progression, unacceptable toxicity, or other protocol-specified withdrawal criteria are met.
干预措施: Ibrutinib (Drug)
结局指标
主要结局
Part 1: Number of Participants With Dose Limiting Toxicity
时间窗: Approximately 9 months
Dose limiting toxicity is based on adverse events and includes unacceptable hematologic toxicity, unacceptable non-hematologic toxicity, and laboratory abnormalities of Grade 4 or higher.
Part 1 and Part 2: Number of Participants With Adverse Events
时间窗: Approximately 2 years
An adverse event (AE) is any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship.
Part 1 and Part 2: Number of Participants With Serious Adverse Events
时间窗: Approximately 2 years
A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital abnormality.
Part 1 and Part 2: Change in Clinical Laboratory Values From Baseline
时间窗: Baseline and 2 years
Standard clinical chemistry and hematology panels will be used to evaluate changes in laboratory parameters in blood samples collected pre- and post-treatment.
次要结局
- Part 1 and Part 2: Area Under the Serum Concentration-Time Curve From Time [0 to t] (AUC[0-t]) of Duvortuxizumab(Approximately 2 years)
- Part 1 and Part 2: Area Under the Serum Concentration-Time Curve From Time [0 to t] (AUC[0-t]) of Ibrutinib(Approximately 2 years)
- Part 1 and 2: Maximum Serum Concentration (Cmax) of Duvortuxizumab(Approximately 2 years)
- Part 1 and 2: Maximum Serum Concentration (Cmax) of Ibrutinib(Approximately 2 years)
- Part 1 and 2: Half-Life (t1/2) of Duvortuxizumab(Approximately 2 years)
- Part 1 and 2: Half-Life (t1/2) of Ibrutinib(Approximately 2 years)
- Part 1 and 2: Total Systemic Clearance (CL) of Duvortuxizumab(Approximately 2 years)
- Part 1 and 2: Total Systemic Clearance (CL) of Ibrutinib(Approximately 2 years)
- Part 1 and 2: Volume of Distribution at Steady-State (Vss) of Duvortuxizumab(Approximately 2 years)
- Part 1 and 2: Volume of Distribution at Steady-State (Vss) of Ibrutinib(Approximately 2 years)
- Part 1 and Part 2: Number of Participants with Anti-Duvortuxizumab Antibodies(Approximately 2 years)
- Part 1 and Part 2: Objective Tumor Response(Approximately 2 years)
- Part 1 and Part 2: Number of Participants With Complete Response (CR)(Approximately 2 years)
- Part 1 and Part 2: Duration of Response(Approximately 2 years)
- Part 1 and Part 2: 1-year Progression Free Survival (PFS)(1 year)
- Part 1 and Part 2: 1-year Overall Survival(1 year)