Selinexor in Combination With R-CHOP as the First-line Therapy for TP53-mutated DLBCL Patients: a Single-arm, Multicenter, Phase II Clinical Trial (Smart Trial)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 42
- 试验地点
- 2
- 主要终点
- Complete response rate (CRR)
研究概览
简要总结
This is a prospective, single-arm, multi-center, phase II clinical trial to evaluate the efficacy and safety of selinexor in combination with R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisone) followed by selinexor maintenance for untreated TP53-mutated diffuse large B-cell lymphoma (DLBCL) patients.
详细描述
The purpose of this phase II clinical trial is to evaluate the efficacy and safety of selinexor in combination with R-CHOP for untreated TP53-mutated DLBCL patients.
The induction phase consisted of 8 cycles of selinexor in combination with R-CHOP. After 8 cycles of induction therapy, if the response is assessed as complete remission (CR), maintenance therapy with selinexor will be conducted.
The primary endpoint is complete response rate.
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
- •Subjects fully understand and voluntarily participate in this study and sign informed consent.
- •Aged ≥18 and ≤80 years, no gender limitation.
- •Histologically confirmed DLBCL with TP53 mutations (allowing transformed or concurrent indolent B-cell non-Hodgkin lymphoma)
- •No prior systemic anti-lymphoma therapy; prior local radiotherapy alone is permitted.
- •There must be at least one measurable or evaluable lesion that meets the evaluation criteria for Lugano 2014 lymphoma.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-
- •Expected survival ≥ 3 months.
- •Adequate function of bone marrow, liver, and kidney.
排除标准
- •DLBCL with Hodgkin lymphoma, T-cell lymphoma, or other non-B-cell lymphoma; Richter transformation.
- •DLBCL with central nervous system invasion.
- •The patients had previously received XPO1 inhibitors.
- •The patients have contraindications to any drug in the combined treatment.
- •Patients with chronic active hepatitis B or active hepatitis C. If the background hepatitis B surface antigen (HBsAg) and/or hepatitis B core Antibody (HBcAb) or hepatitis C Virus (HCV) antibody are positive, the further determination for Hepatitis B Virus (HBV) DNA (no more than 2500 copies /mL or 500 IU/mL) and HCV RNA (no more than the lower limit of the assay) can be included. The patients with HBsAg and/or HBcAb positive need to receive anti-HBV drugs.
- •Patients with the infection of human immunodeficiency virus (HIV) and/or acquired immunodeficiency syndrome.
- •Inability to swallow tablets, presence of malabsorption syndrome, or any other gastrointestinal disease or dysfunction that may affect the absorption of the study drug.
- •Pregnant and lactating women and subjects of childbearing age who do not want to use contraception.
- •Mentally ill persons or persons unable to obtain informed consent.
- •Any condition deemed unsuitable by the investigator.
研究组 & 干预措施
Selinexor in combination with R-CHOP
Patients with TP53-mutated diffuse large B-cell lymphoma will receive selinexor in combination with R-CHOP regimen from the second cycle of R-CHOP (3 weeks per cycle).
After 8 cycles of induction therapy, if the response is assessed as complete remission (CR), maintenance therapy with selinexor will be conducted.
干预措施: Selinexor Oral Tablet [Xpovio] (Drug)
Selinexor in combination with R-CHOP
Patients with TP53-mutated diffuse large B-cell lymphoma will receive selinexor in combination with R-CHOP regimen from the second cycle of R-CHOP (3 weeks per cycle).
After 8 cycles of induction therapy, if the response is assessed as complete remission (CR), maintenance therapy with selinexor will be conducted.
干预措施: R-CHOP Protocol (Drug)
结局指标
主要结局
Complete response rate (CRR)
时间窗: Up to 8 cycles (each cycle is 21 days)
To investigate the preliminary anti-tumor efficacy
次要结局
- Disease-free survival (DFS)(From date of the first complete response until the date of the first documented progression or date of death from any cause, whichever came first, assessed up to 24 months)
- Progression-free survival (PFS)(From the date of enrollment until the date of the first documented progression or date of death from any cause, whichever came first, assessed up to 24 months)
- Overall survival (OS)(From the date of enrollment until the date of death from ant cause, assessed up to 24 months)
- Number of participants with adverse events (AE) and severe adverse events (SAE) as assessed by CTCAE v5.0(Through study completion, an average of 2 years)
- Duration of response (DOR)(From date of the first CR or PR to the first documented progressive disease or death, whichever occurred earlier, assessed up to 24 months)
- Time to response (TTR)(From the date of enrollment until the first response, assessed up to 24 weeks)
- Objective response rate (ORR)(Up to 8 cycles (each cycle is 21 days))
研究者
Qingqing Cai
chief physician
Sun Yat-sen University