An Open-label, Multicenter, Exploratory Clinical Study of the EZH2 Inhibitor Zeprumetostat in Combination Therapy for Patients With Relapsed or Refractory Mature T-cell and NK-cell Lymphomas.
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 60
- 主要终点
- DLT for Phase 1b
研究概览
简要总结
This is a prospective, multicenter, open-label, phase Ib/II clinical study to evaluate the safety and efficacy of EZH2 inhibitor Zeprumetostat in combination therapy for patients with relapsed or refractory mature T-cell and NK-cell lymphomas.
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
- •Voluntarily participate in the clinical study; fully understand and be informed about the study and sign the Informed Consent Form (ICF); willing to comply with and capable of completing all trial procedures;
- •Age ≥ 18 years
- •Pathologically confirmed mature T-cell and NK-cell lymphomas.
- •Using the Lugano 2014 criteria, the patient must have at least one measurable or evaluable lesion
- •Participants must have experienced disease progression, treatment failure, or intolerance following standard therapy. Patients with ALCL are required to have previously received anti-CD30-targeted therapy, while patients with NKTCL must have previously been treated with pegaspargase or L-asparaginase.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- •Adequate organ and bone marrow function
排除标准
- •Lymphoma involvement in the central nervous system or meninges
- •Active infections
- •Prior treatment with an EZH2 inhibitor or an EZH1/2 dual inhibitor that was discontinued due to intolerance to toxicity;
- •For patients enrolled in Cohort 1, prior treatment with a JAK inhibitor that was discontinued due to intolerance to toxicity;
- •For patients enrolled in Cohort 2, prior treatment with an HDAC inhibitor that was discontinued due to intolerance to toxicity.
- •History of Human Immunodeficiency Virus (HIV) infection and/or Acquired Immunodeficiency Syndrome (AIDS).
- •Patients with mental disorders or those unable to provide informed consent
- •Any other condition deemed by the investigator to be unsuitable for study enrollment;
- •Pregnant or breastfeeding women, and subjects of childbearing potential who are unwilling to use contraception;
- •Individuals with a known hypersensitivity to any of the investigational drugs.
研究组 & 干预措施
Zeprumetostat Combined with Golidocitinib or Chidamide
In Cohort 1, patients will receive Zeprumetostat in combination with Golidocitinib, with an initial dose of 350mg of Zeprumetostat. Each treatment cycle is 28 days. The Zeprumetostat will be combined with Golidocitinib at the RP2D dose level for an extension study. In Cohort 2, patients will receive Zeprumetostat in combination with Chidamide, with an initial dose of 350mg of Zeprumetostat. Each treatment cycle is 28 days. The Zeprumetostat will be combined with Chidamide at the RP2D dose level for an extension study.
干预措施: Zeprumetostat (Drug)
Zeprumetostat Combined with Golidocitinib or Chidamide
In Cohort 1, patients will receive Zeprumetostat in combination with Golidocitinib, with an initial dose of 350mg of Zeprumetostat. Each treatment cycle is 28 days. The Zeprumetostat will be combined with Golidocitinib at the RP2D dose level for an extension study. In Cohort 2, patients will receive Zeprumetostat in combination with Chidamide, with an initial dose of 350mg of Zeprumetostat. Each treatment cycle is 28 days. The Zeprumetostat will be combined with Chidamide at the RP2D dose level for an extension study.
干预措施: Golidocitinib (Drug)
Zeprumetostat Combined with Golidocitinib or Chidamide
In Cohort 1, patients will receive Zeprumetostat in combination with Golidocitinib, with an initial dose of 350mg of Zeprumetostat. Each treatment cycle is 28 days. The Zeprumetostat will be combined with Golidocitinib at the RP2D dose level for an extension study. In Cohort 2, patients will receive Zeprumetostat in combination with Chidamide, with an initial dose of 350mg of Zeprumetostat. Each treatment cycle is 28 days. The Zeprumetostat will be combined with Chidamide at the RP2D dose level for an extension study.
干预措施: Chidamide (Drug)
结局指标
主要结局
DLT for Phase 1b
时间窗: The first cycle after administration (each cycle is 28 days)
To identify the dose-limiting toxicity
Overall response rate(ORR) for Phase 2
时间窗: Up to 24 months
The proportion of patients who achieve complete remission (CR) or partial remission (PR) as the best response.
RP2D for phase Ib
时间窗: The first cycle after administration (each cycle is 28 days)
To identify the recommended phase 2 dose
次要结局
- Complete response rate (CRR)(Up to 24 months)
- Duration of Response(DOR)(Up to 4 years)
- Progression-free survival(PFS)(Up to 4 years)
- Overall survival(OS)(Up to 4 years)
研究者
Qingqing Cai
Principal Investigator
Sun Yat-sen University