Orelabrutinib Combined With Rituximab ± Lenalidomide in Response-Adapted Stratified Therapy for Untreated MZL#a Prospective Single Arm Trial
概览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Complete response rate (CRR)
概览
简要总结
This is a prospective, single-arm, phase II study aimed at evaluating the safety and efficacy of orelabrutinib combined with rituximab ± lenalidomide in response-adapted stratified therapy for untreated marginal zone lymphoma. The primary endpoint is the complete response rate (CRR).
详细描述
Marginal zone lymphoma (MZL) is a type of lymphoma that comprises three main subtypes: extranodal mucosa-associated lymphoid tissue (MALT) lymphoma, nodal MZL, and splenic MZL. Accounting for approximately 7.8% of all non-Hodgkin lymphomas (NHL), MZL is the third most common subtype, following diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). Although generally considered an indolent lymphoma with a favorable overall survival prognosis, some patients still face challenges such as disease relapse or transformation into aggressive large cell lymphoma, which leads to a poor prognosis.
This is a prospective, single-arm, phase II study designed to evaluate the safety and efficacy of orelabrutinib combined with rituximab ± lenalidomide in response-adapted stratified therapy for untreated marginal zone lymphoma. Eligible patients who meet the screening criteria will enter the treatment phase and receive orelabrutinib in combination with rituximab. After 6 cycles, patients who achieve complete response (CR) will continue with orelabrutinib and rituximab for an additional 6 cycles; patients with partial response (PR) or stable disease (SD) will receive orelabrutinib combined with rituximab and lenalidomide for an additional 6 cycles; patients with progressive disease (PD) will be withdrawn from the study.
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
- •Aged ≥18 years, either sex.
- •Histopathologically confirmed CD20-positive marginal zone lymphoma (including MALT, SMZL, and NMZL) with at least 1 measurable lesion.
- •Stage III or IV disease with an indication for treatment.
- •No prior systemic therapy. Patients may have received prior local treatment (including surgery, radiotherapy, anti-Helicobacter pylori therapy, or anti-hepatitis C therapy) if they subsequently progressed, relapsed, or were unsuitable for local therapy.
- •ECOG performance status of 0-
- •Adequate organ function meeting the following criteria:
- •Blood count: Absolute neutrophil count ≥1.5×10⁹/L, platelets ≥75×10⁹/L, hemoglobin ≥75 g/L. If bone marrow involvement is present: absolute neutrophil count ≥1.0×10⁹/L, platelets ≥50×10⁹/L, hemoglobin ≥50 g/L.
- •Blood chemistry: Total bilirubin ≤1.5×ULN, AST or ALT ≤2×ULN; serum creatinine ≤1.5×ULN; serum amylase ≤ULN.
- •Coagulation: International normalized ratio (INR) ≤1.5×ULN.
- •Expected survival ≥12 months.
排除标准
- •Current or history of other malignancies, unless treated with curative intent and without evidence of recurrence or metastasis within the past 5 years.
- •Central nervous system involvement or transformation to high-grade lymphoma.
- •Uncontrolled or significant cardiovascular diseases, including:
- •New York Heart Association (NYHA) Class II or higher congestive heart failure, unstable angina, myocardial infarction within 6 months prior to the first study drug dose, or arrhythmia requiring treatment at screening; left ventricular ejection fraction (LVEF) \<50%.
- •Primary cardiomyopathy (e.g., dilated, hypertrophic, arrhythmogenic right ventricular, restrictive, or unclassified cardiomyopathy).
- •History of clinically significant QTc interval prolongation, or QTc interval \>470 ms (female) or \>450 ms (male) at screening.
- •Symptomatic coronary artery disease or subjects requiring medication for it.
- •Poorly controlled hypertension (defined as failure to achieve target blood pressure after ≥1 month of lifestyle modification combined with an adequate, tolerable regimen of ≥3 antihypertensive drugs including a diuretic, or requiring ≥4 antihypertensive drugs for control).
- •Active bleeding within 2 months prior to screening, current use of anticoagulants, or any condition deemed by the investigator to indicate a clear bleeding tendency.
- •History of deep vein thrombosis or pulmonary embolism within the past 6 months.
研究组 & 干预措施
Orelabrutinib Combined with Rituximab ± Lenalidomide
干预措施: Orelabrutinib (Drug)
Orelabrutinib Combined with Rituximab ± Lenalidomide
干预措施: Rituximab (Drug)
Orelabrutinib Combined with Rituximab ± Lenalidomide
干预措施: Lenalidomide (Drug)
结局指标
主要结局
Complete response rate (CRR)
时间窗: At the end of cycle 12 (each cycle is 21 days)
CRR is defined as the proportion of patients with complete response
次要结局
- Overall response rate (ORR)(At the end of cycle 12(each cycle is 21 days))
- 2 years Progression free survival (PFS)(From date of signing the informed consent until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years)
- 2 years overall survival (OS)(From date of signing the informed consent until the date of death from any cause, whichever came first, assessed up to 2 years)