A Prospective, Open-Label, Single-Arm, Phase 2, Multicenter Study Evaluating the Efficacy of Venetoclax Plus Ibrutinib in Subjects With T-Cell Prolymphocytic Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 14
- 试验地点
- 15
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
The main objective of this study is to evaluate the efficacy of the combination of venetoclax plus ibrutinib for treating adults with T-cell prolymphocytic leukemia (T-PLL).
详细描述
This study is planned as an adaptive 2-stage design as follows:
Stage 1: Enroll 14 participants with relapsed or refractory (R/R) T-PLL and move to Stage 2 if 4 or more participants meet protocol-specified response criteria. Response assessment will be performed on a continued basis until all 14 participants have enrolled into Stage 1 and have completed the Week 24 disease assessment.
Stage 2: Enroll up to an additional 23 participants.
The study was stopped after Stage 1. Stage 2 was not conducted.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adequate liver, kidney and hematology function per laboratory values as described in the protocol.
- •Diagnosis of T-cell prolymphocytic leukemia (T-PLL) that requires treatment.
- •Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to
- •Received prior alemtuzumab (unless unsuitable or unavailable).
- •Has no malignancies other than T-PLL that:
- •currently require systemic therapies;
- •were not previously treated with curative intention (unless the malignant disease is in a stable remission due to the discretion of the treating physician); or
- •developed signs of progression after curative treatment.
排除标准
- •History of or current decompensated cirrhosis including Child-Pugh class B or C, ascites, hepatic encephalopathy, or variceal bleeding.
- •Has human T-cell lymphotropic virus, type
- •Prior allogeneic stem cell transplant within 6 months of study drug administration and requirement for graft versus host therapy.
- •Has an uncontrolled or active infection including severe acute respiratory syndrome- coronavirus-2 (SARS-COV-2).
- •Previously treated with a B-cell lymphoma (BCL)-2 inhibitor.
- •Received a prohibited therapy within the specified time frame as described in the protocol.
研究组 & 干预措施
Venetoclax + Ibrutinib
Participants received 400 mg venetoclax orally once a day after a 5-day ramp-up and 420 mg ibrutinib orally once a day for up to 2 years or until progressive disease, intolerability, or they became eligible for stem cell transplantation after achieving complete remission.
干预措施: Venetoclax (Drug)
Venetoclax + Ibrutinib
Participants received 400 mg venetoclax orally once a day after a 5-day ramp-up and 420 mg ibrutinib orally once a day for up to 2 years or until progressive disease, intolerability, or they became eligible for stem cell transplantation after achieving complete remission.
干预措施: Ibrutinib (Drug)
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: Clinical response was assessed at Weeks 4, 8, 12, 16, and 24 for ORR assessment
ORR is defined as the percentage of participants achieving complete remission (CR), CR with incomplete bone marrow recovery (CRi), or partial remission (PR) as their best response per investigator assessment based on the T-PLL consensus criteria 2019. CR: All of the following response criteria must be met: Group A: * all lymph nodes \< 1 cm; * spleen \< 13 cm; * no constitutional symptoms; * circulating lymphocyte count \< 4 × 10\^9/L; * bone marrow T-PLL cells \< 5% of mononuclear cells; * no other specific site involvement Group B: * platelets ≥ 100 × 10\^9 /L; * hemoglobin ≥ 11.0 g/dL; * neutrophils ≥ 1.5 × 10\^9 /L. CRi: All of the CR response criteria in Group A met; at least 1 parameter in Group B not achieved, unrelated to T-PLL, but related to drug toxicity. PR: At least 2 of the parameters in Group A and 1 parameter in Group B need to improve if previously abnormal. If only 1 parameter of both Groups A and B is abnormal prior to therapy, only 1 parameter needs to improve.
次要结局
- Number of Eligible Participants Reaching Autologous or Allogeneic Transplantation(From first dose of study drug to end of study; median time on study was 30.1 weeks.)
- Event-free Survival (EFS)(From first dose of study drug to end of study; median time on study was 30.1 weeks.)
- Progression-Free Survival (PFS)(From first dose of study drug to end of study; median time on study was 30.1 weeks.)
- Duration of Response (DOR)(From first dose of study drug to end of study; median time on study was 30.1 weeks.)
- Time to Progression (TTP)(From first dose of study drug to end of study; median time on study was 30.1 weeks.)
- Overall Survival (OS)(From first dose of study drug to end of study; median time on study was 30.1 weeks.)
- Number of Participants With Treatment-emergent Adverse Events (TEAE)(From first dose of study drug up to 30 days after last dose; median time on treatment was 13.86 weeks (range 1.0 to 44.4 weeks))
- Disease Control Rate (DCR)(Clinical response was assessed at Weeks 4, 8, 12, 16, and 24 for DCR assessment)