A Prospective, Multicenter, Single-arm Clinical Study on the Treatment of Newly Diagnosed Diffuse Large B-cell Lymphoma With High-risk of CNS Relapse Defined by CNS-IPI Using Orelabrutinib in Combination With R-CDOP Regimen
概览
- 阶段
- 2 期
- 干预措施
- Orelabrutinib combined with R-CDOP regimen
- 疾病 / 适应症
- Diffuse Large B-cell Lymphoma
- 发起方
- Second Affiliated Hospital, School of Medicine, Zhejiang University
- 入组人数
- 62
- 试验地点
- 6
- 主要终点
- 2-year central nervous system relapse rate
- 状态
- 招募中
- 最后更新
- 2年前
概览
简要总结
This is a prospective, multicenter, single-arm clinical study on the treatment of newly diagnosed diffuse large B-cell lymphoma with high-risk of CNS relapse defined by CNS-IPI using Orelabrutinib in combination with R-CDOP regimen.
详细描述
Diffuse large B-cell lymphoma (DLBCL) is an aggressive form of B-cell lymphoma, where the dual expression of Myc and BCL-2 genes in non-germinal center B-cell like (non-GCB) lymphomas is associated with a poor prognosis when treated with the standard R-CHOP regimen. Bruton's tyrosine kinase (BTK), a key kinase in the B-cell receptor (BCR) signaling pathway, is an important target for the treatment of B-cell lymphomas. Studies have shown that the first-generation BTK inhibitor Ibrutinib when combined with the R-CHOP regimen for previously untreated patients with dual-expressing, non-GCB lymphomas, can improve event-free survival rates. Orelabrutinib, as a new generation BTK inhibitor independently developed in China, possesses higher inhibitory activity against BTK kinase and can penetrate the blood-brain barrier, offering potential benefits for patients at high risk of central nervous system relapse. The novel anthracycline drug-Liposomal Doxorubicin, which has almost no cardiac toxicity, suggests that the combination of Orelabrutinib with the R-CDOP regimen could improve the adverse prognosis of DLBCL patients at high risk of central relapse. This is a prospective, multicenter, single-arm clinical study on the treatment of newly diagnosed diffuse large B-cell lymphoma with high-risk CNS-IPI using Orelabrutinib in combination with R-CDOP regimen. All participants were treated with the Orelabrutinib combined with R-CDOP regimen. The treatment cycles were set every 21 days for a total of 6-8 cycles. During the study treatment period, researchers conducted a tumor assessment (with a 1-week time window allowed) after the screening period and once again after the 4th, 6th, or 8th cycle of treatment to evaluate the antitumor efficacy of the investigational drug. After all treatment cycles were completed, follow-up visits were conducted every 3 months until the end of the 3-year period. The median duration of follow-up was 24 months.
研究者
入排标准
入选标准
- •Age ≥18 years old; ECOG score 0-3;
- •Histologically confirmed diffuse large B-cell lymphoma, including DLBCL and transformed DLBCL;
- •CNS-IPI≥4 points
- •Previously untreated participants with CD20-positive DLBCL,;
- •Heart, liver, and kidney function: creatinine \< 2 times the normal upper limit (ULN); ALT (alanine aminotransferase)/AST (Aspartate Aminotransferase) \< 2.5ULN; Total bilirubin \< 2ULN; Cardiac ejection fraction (EF) ≥50%.
- •At least one measurable lesion.
- •Have the sufficient understanding ability and voluntarily sign informed consent.
排除标准
- •Patients with evidence of CNS involvement ;
- •Clinically significant active cardiovascular disease, such as uncontrolled arrhythmia, uncontrolled hypertension, congestive heart failure, any grade 3 or 4 heart disease as determined by the New York Heart Association (NYHA) functional scale, or a history of myocardial infarction within 6 months before screening;
- •Human immunodeficiency virus (HIV) infection;
- •Pregnant or lactating women;
- •Other tumors that require treatment;
- •Uncontrolled active infection;
- •The HBV DNA copy number of active hepatitis after antiviral treatment can not be controlled within 2×103/ml.
- •unable to understand and follow the research protocol or unable to sign the informed consent.
研究组 & 干预措施
Orelabrutinib combined with R-CDOP regimen
Participants will receive 150 mg of oral orelabrutinib once daily with R-CDOP on day 1 of each cycle (21 days)
干预措施: Orelabrutinib combined with R-CDOP regimen
结局指标
主要结局
2-year central nervous system relapse rate
时间窗: up to 2 years
The proportion of patients with central nervous system recurrence within two years from enrollment accounted for all patients treated with drugs.
次要结局
- 2-year Overall survival (OS) rate(Up to 2 years)
- 1-year Overall survival (OS) rate(Up to 1 year)
- Complete Response Rate(At the end of Cycle 3 and Cycle 6（each cycle is 21 days）)
- Overall Response Rate (ORR)(At the end of Cycle 3 and Cycle 6（each cycle is 21 days）)
- 1-year progression-free survival (PFS) rate(1 year after enrollment of final patient)
- 2-year progression-free survival (PFS) rate(2 years after enrollment of final patient)
- Occurrence of hematologic adverse events and non-hematologic adverse events according to CTCAE V4.03(Up to 3 years)