A Prospective Phase 2 Study of Lisaftoclax Plus Pirtobrutinib in Patients With Relapsed or Refractory Mantle Cell Lymphoma After Failure of BTK-Targeted Therapy
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- Complete Response Rate at 6 Months in Cohort 1
研究概览
简要总结
This prospective, open-label, phase 2 study will evaluate the efficacy and safety of lisaftoclax in combination with pirtobrutinib in adults with relapsed or refractory mantle cell lymphoma following failure of prior BTK-targeted therapy.
The study includes two cohorts. Cohort 1 will enroll participants who experienced stable disease, disease progression, or intolerance following treatment with a covalent BTK inhibitor. Cohort 2 is an exploratory cohort enrolling participants who experienced stable disease, disease progression, or intolerance following treatment with a non-covalent BTK inhibitor other than pirtobrutinib or a BTK degrader.
Participants will receive oral pirtobrutinib 200 mg once daily in combination with oral lisaftoclax. Lisaftoclax will be administered using a dose ramp-up schedule, followed by a target dose of 600 mg once daily. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent.
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
- •Participants must meet all of the following criteria:
- •Age 18 years or older.
- •Histologically and immunophenotypically confirmed mantle cell lymphoma.
- •At least one measurable lesion.
- •Received at least one prior systemic treatment regimen that included a BTK-targeted therapy, including a covalent BTK inhibitor, non-covalent BTK inhibitor, or BTK degrader, and had stable disease, disease progression, or intolerance during or after the most recent BTK-targeted therapy.
- •Eastern Cooperative Oncology Group performance status of 0 to
- •Adequate hepatic, renal, and bone marrow function, defined as all of the following:
- •* Aspartate aminotransferase and alanine aminotransferase ≤3 × upper limit of normal;
- •Total bilirubin ≤1.5 × upper limit of normal;
- •Creatinine clearance ≥30 mL/min;
- •Absolute neutrophil count ≥0.5 × 10^9/L;
- •Platelet count ≥30 × 10^9/L. Supportive treatment is permitted.
- •Participants of reproductive potential must agree to use effective contraception during study treatment and for 3 months after the last dose of study treatment.
- •Willing and able to comply with study procedures and follow-up assessments.
- •Able to understand and voluntarily sign the informed consent form before screening.
排除标准
- •1. Known hypersensitivity to pirtobrutinib, lisaftoclax, or any component or excipient of either study drug.
- •2. Concurrent participation in another clinical study.
- •Prior treatment with any BCL-2 inhibitor.
- •Active central nervous system involvement, including parenchymal or leptomeningeal disease.
- •5. Clinically significant uncontrolled cardiac or cardiovascular disease, or a history of myocardial infarction within 6 months before the planned initiation of pirtobrutinib.
- •6. Uncontrolled active severe systemic bacterial, viral, fungal, or parasitic infection.
- •7. Current treatment with strong CYP3A4 inhibitors or inducers and/or strong P-glycoprotein inhibitors.
- •8. Positive human immunodeficiency virus test.
- •Active hepatitis B or hepatitis C infection, except:
- •Participants with detectable hepatitis B virus DNA whose disease is controlled may be enrolled at the investigator's discretion, provided that concurrent antiviral therapy is administered;
- •Participants with a history of hepatitis C virus infection who have completed antiviral treatment and have a viral load below the lower limit of quantification may be enrolled.
- •10. Pregnant or breastfeeding women.
- •Unable to complete protocol-required study visits or procedures, including follow-up visits, or unable to comply with study requirements.
- •12. Any other clinically significant current or prior medical condition that, in the investigator's judgment, may pose a risk to participant safety or interfere with study assessments, procedures, or completion.
结局指标
主要结局
Complete Response Rate at 6 Months in Cohort 1
时间窗: At 6 months after initiation of study treatment
The proportion of participants in Cohort 1 who achieve a complete response at 6 months after initiation of study treatment, as assessed by the investigator according to the Lugano 2014 response criteria.
Overall Response Rate in Cohort 2
时间窗: From the first dose of study treatment until disease progression, assessed up to 36 months
The proportion of participants in Cohort 2 who achieve a best overall response of complete response or partial response, as assessed by the investigator according to the Lugano 2014 response criteria.
次要结局
- Duration of Response(From the first documented response until disease progression or death, whichever came first, assessed up to 36 months)
- Progression-Free Survival(From the first dose of study treatment until disease progression or death, whichever came first, assessed up to 36 months)
- Overall Survival(From the first dose of study treatment until death from any cause, assessed up to 36 months)
- Minimal Residual Disease Negativity Rate(At baseline, assessed up to 4 weeks. Interim response assessment, from the first dose of study treatment till 3 cycles. End of induction treatment, from the first dose of study treatment till 3 cycles. Following period, every 6 months during follow-up.)
- Number of Participants With Treatment-Emergent Adverse Events(From the first dose of study treatment through 30 days after the last dose)
研究者
KeshuZhou
Doctor
Henan Cancer Hospital