A Multi Cohort Exploratory Clinical Study of the EZH2 Inhibitor Zeprumetostat Combination Regimen in Relapsed/Refractory Peripheral T Cell Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 33
- 试验地点
- 1
- 主要终点
- Summary of DLT events (Phase Ib)
研究概览
简要总结
This is a single-arm, multi-cohort, multicenter, phase Ib/IIa clinical study designed to evaluate the safety and efficacy of Zeprumetostat (an EZH2 inhibitor) in combination with different therapeutic agents/regimens - specifically, the JAK1 inhibitor golidocitinib and the GemOx chemotherapy regimen (gemcitabine plus oxaliplatin) - in patients with relapsed or refractory peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) and T-follicular helper cell lymphoma (TFHL). The trial comprises a phase Ib dose-escalation phase and a phase IIa dose-expansion phase. Two combination cohorts are established: Cohort A (zemitostatin + golidocitinib) and Cohort B (zemitostatin + GemOx). Subjects will be randomly assigned to either Cohort A or Cohort B.
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
- •Age 18 years or older, both males and females are eligible;
- •Histologically confirmed peripheral T-cell lymphoma (PTCL) including PTCL-NOS and TFHL that has relapsed or is refractory after at least one line of systemic therapy. The definitions are as follows:
- •Relapse: Patients who achieved a Complete Response (CR) in previous treatments and have new lesions at the original site or elsewhere; Refractory: Patients who did not achieve CR after adequate treatment. For nasal-type NK/T-cell lymphoma, previous treatments must have included a chemotherapy regimen containing asparaginase;
- •Patients who have undergone prior hematopoietic stem cell transplantation are allowed;
- •ECOG PS 0-2
- •Life expectancy greater than 3 months.
- •Adequate organ function
- •Contraception during study
- •Informed consented
排除标准
- •Prior treatment with EZH2 inhibitors or EZH1/2 inhibitors before enrollment;
- •Peripheral T-cell lymphoma of subtypes other than PTCL-NOS and TFHL;
- •History of other primary invasive malignancies that have not been in remission or have been in remission for no more than 3 years;
- •Central nervous system involvement (meningeal or parenchymal);
- •Known hypersensitivity to any study drugs;
- •Participation in another clinical trial of an investigational drug within 4 weeks prior to the start of the study.
- •Pregnant or lactation
- •Active infection.
- •Diseases and medical history:
- •Requires continuous treatment with strong or moderate CYP3A inhibitors or CYP3A inducers
- •Has multiple factors affecting oral medication administration (e.g., inability to swallow, chronic diarrhea, intestinal obstruction, etc.);
- •Has a history of psychoactive substance abuse that cannot be discontinued
- •Has any severe and/or uncontrolled disease.
- •Uncontrollable autoimmune disease,
- •Not able to comply to the protocol for mental or other unknown reasons
- •Any other condition that, in the investigator's judgment, makes the patient unsuitable for study participation.
结局指标
主要结局
Summary of DLT events (Phase Ib)
时间窗: At the end of Cycle 1 (each cycle is 21 days)
A Phase Ib Dose-Finding Study of Zeprumetostat in Combination Using a 3+3 Design
Overall response rate (Phase Ⅱ)
时间窗: Through study completion, an average of 2 years after EZH2+JAK1/GemOx (Day 1)
Objective Response Rate (ORR) is defined as the proportion of subjects who achieve CR or PR after treatment EZH2+JAK1/GeMox
次要结局
- Complete response rate(Through study completion, an average of 2 years after EZH2+JAK1/GemOx (Day 1))
- Duration of response(Through study completion, an average of 2 years after EZH2+JAK1/GemOx (Day 1))
- Progression free survival(Through study completion, an average of 2 years after EZH2+JAK1/GemOx (Day 1))
- Overall survival(Through study completion, an average of 3 years after EZH2+JAK1/GemOx (Day 1))
- Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE(Through study completion, an average of 2 years after EZH2+JAK1/GemOx (Day 1))