A Prospective, Multicenter, Single-Arm, Open-Label Phase 2 Study of Chidamide Maintenance in Patients With Newly Diagnosed Double-Expressor Diffuse Large B-Cell Lymphoma Who Achieve Complete Response After Induction Therapy But Remain ctDNA MRD-Positive
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 69
- 试验地点
- 1
研究概览
简要总结
This is a prospective, multicenter, single-arm, open-label phase 2 study designed to evaluate the efficacy and safety of chidamide maintenance in adults with newly diagnosed double-expressor diffuse large B-cell lymphoma (DLBCL) who achieve complete response after induction therapy but remain ctDNA minimal residual disease (MRD)-positive. Eligible participants will receive oral chidamide 20 mg on Days 1, 4, 8, and 11 of each 21-day cycle. ctDNA MRD will be assessed every 12 weeks. Treatment will continue until two consecutive MRD-negative assessments, disease progression, intolerable toxicity, withdrawal of consent, or completion of 2 years of maintenance. The primary objectives are to evaluate ctDNA MRD negativity and 2-year progression-free survival. Secondary objectives include event-free survival, overall survival, and safety.
详细描述
Patients with double-expressor DLBCL remain at increased risk of relapse despite achieving complete response after induction therapy. ctDNA-based MRD assessment may identify a subgroup with persistent molecular disease who are at particularly high risk for recurrence. Chidamide is an oral selective histone deacetylase inhibitor with potential antitumor and immune-modulating activity in B-cell lymphomas.
This prospective, multicenter, single-arm, open-label phase 2 study will enroll adult patients with newly diagnosed CD20-positive double-expressor DLBCL, defined by MYC expression >=40% and BCL2 expression >=50% by immunohistochemistry, who achieve complete response after initial induction therapy but remain ctDNA MRD-positive. Participants will receive chidamide 20 mg orally on Days 1, 4, 8, and 11 of each 21-day cycle. ctDNA MRD will be monitored every 12 weeks. Treatment will stop upon two consecutive MRD-negative assessments, disease progression, intolerable toxicity, withdrawal of consent, or completion of 2 years of maintenance. The study will evaluate ctDNA MRD negativity rate and 2-year progression-free survival as primary endpoints, with event-free survival, overall survival, and safety as secondary endpoints.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed diffuse large B-cell lymphoma, CD20-positive.
- •Double-expressor lymphoma confirmed by pathology, defined as MYC expression >=40% and BCL2 expression >=50% by immunohistochemistry.
- •Complete response after initial induction therapy.
- •Age >=18 and <=80 years.
- •ECOG performance status 0-
- •No prior history of malignant tumor and no concurrent malignancy.
- •International Prognostic Index (IPI) score >
- •ctDNA MRD-positive at screening/enrollment.
- •Life expectancy of at least 6 months, in the opinion of the investigator.
- •Written informed consent provided before any study-specific procedure.
排除标准
- •Failure to achieve complete response after initial induction therapy.
- •Prior organ transplantation.
- •Uncontrolled coagulopathy or active bleeding.
- •Uncontrolled cardiovascular or cerebrovascular disease, including left ventricular ejection fraction <50%, connective tissue disease, or severe active infection.
- •Major organ surgery within 6 weeks before screening.
- •Screening laboratory abnormalities not attributable to lymphoma, including: neutrophil count <1.5 x 10^9/L; platelet count <80 x 10^9/L (or <50 x 10^9/L in patients with bone marrow involvement); total bilirubin >1.5 x upper limit of normal; ALT/AST >2.5 x upper limit of normal, or >5 x upper limit of normal in patients with hepatic involvement; serum creatinine >1.5 x upper limit of normal.
- •Active hepatitis B not meeting protocol-defined virologic criteria for enrollment; patients with positive HBsAg or positive HBcAb require HBV DNA testing and must meet protocol-specified thresholds.
- •HIV infection.
- •Ongoing antitumor therapy for lymphoma or another malignancy.
- •Drug abuse or chronic alcohol abuse that may interfere with study evaluation.
- •Psychiatric illness or any condition resulting in inability to comply with the protocol.
- •Requirement for ongoing treatment with strong or moderate CYP3A inhibitors or inducers; patients exposed to these agents within 7 days before first study dose, or within fewer than 5 half-lives, are not eligible.
- •Inability to swallow capsules or clinically significant gastrointestinal disorders that may affect drug absorption, including malabsorption syndrome, bariatric surgery, inflammatory bowel disease, or partial/complete bowel obstruction.
- •Any other uncontrolled medical condition that, in the investigator's judgment, may compromise safety, interfere with oral drug absorption or metabolism, or place the participant at excessive risk.
研究者
Rong Tao
MD & PhD
Fudan University