Zanubrutinib, Obinutuzumab, and Lenalidomide (ZGR) in the Treatment of Newly Diagnosed Splenic B-cell Lymphoma With Prominent Nucleoli (SBLPN): A Prospective, Open-label, Single-arm Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 47
- 试验地点
- 1
- 主要终点
- Objective response rate，ORR
研究概览
简要总结
:The aim of this study was to analyze the safety and efficacy of Zanubrutinib, Obinutuzumab, and Lenalidomide (ZGR) in the Treatment of Newly Diagnosed Splenic B-cell Lymphoma with Prominent Nucleoli (SBLPN).
The main questions it aims to explore the Preliminary Efficacy of the Zanubrutinib, Obinutuzumab, and Lenalidomide (ZGR) Regimen in the Treatment of Newly Diagnosed SBLPN Patients.
To explore the safety of zanubrutinib, obinutuzumab combined with lenalidomide (ZGR) in the treatment of newly diagnosed SBLPN patients.
详细描述
There is no consensus on optimal first-line therapy for splenic B-cell lymphoproliferative neoplasms (SBLPN). Existing regimens like cladribine/bendamustine plus rituximab face toxicity and resistance. Targeting Bruton's tyrosine kinase (BTK), the novel BTK inhibitor zanubrutinib (highly selective, low toxicity) combined with obinutuzumab (enhanced antibody-dependent cytotoxicity) and lenalidomide (immunomodulation) shows promise. This single-arm trial evaluates the ZGR regimen (zanubrutinib, obinutuzumab, lenalidomide) for untreated SBLPN, including 6-cycle induction and maintenance therapy (zanubrutinib-lenalidomide), aiming to enhance efficacy, survival, and tolerability, offering a novel approach for this rare disease.
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
- •Aged 18 to 80 years, male or female
- •Histologically or cytologically confirmed SBLPN requiring active treatment;
- •No prior systemic therapy for SBLPN received;
- •ECOG performance status of 0-2;
- •Anticipated life expectancy ≥6 months;
- •Laboratory parameters (hematologic and biochemical) meeting the following criteria:
- •a. Absolute neutrophil count (ANC) ≥1.0 × 10⁹/L, platelet count ≥50 × 10⁹/L;
- •b. Total bilirubin (TBIL) ≤2.0 × upper limit of normal (ULN);
- •c. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN;
- •d. Creatinine clearance ≥50 mL/min (calculated via Cockcroft-Gault formula or direct measurement).
- •Men and women of childbearing potential must agree to use medically approved contraception throughout the study and for 4 weeks after treatment discontinuation;
- •Participants must voluntarily enroll in the study and provide written informed consent.
排除标准
- •History of central nervous system (CNS) disorders (including CNS lymphoma) diagnosed within 1 year prior to enrollment.
- •Other primary malignancies within the past 3 years (excluding non-melanoma skin cancer, curatively treated localized prostate cancer, cervical carcinoma in situ, or squamous intraepithelial lesions on PAP smear).
- •Exposure to any investigational drugs, antimicrobial agents, or participation in other interventional clinical trials within 4 weeks prior to enrollment.
- •Major surgery (excluding lymph node biopsy) within 14 days before enrollment or anticipated requirement for major surgery during the study.
- •Prior use of investigational agents targeting SBLPN.
- •Active immunodeficiency, autoimmune diseases, prolonged systemic corticosteroid therapy (>10 mg/day prednisone equivalent) within 7 days prior to enrollment, or any immunosuppressive therapy.
- •Severe hepatic dysfunction (e.g., severe jaundice, hepatic encephalopathy, refractory ascites, hepatorenal syndrome), cachexia, multiorgan failure, or severe renal impairment.
- •Clinically significant cardiovascular comorbidities:
- •New York Heart Association (NYHA) class III/IV heart failure; Myocardial infarction within 6 months prior to enrollment; Uncontrolled arrhythmias (including QTc interval ≥480 ms); Poorly controlled hypertension (systolic ≥150 mmHg/diastolic ≥100 mmHg despite antihypertensives); Unstable angina.
- •Bleeding diathesis or coagulation disorders; thrombotic events within 3 months prior to enrollment.
- •Hypersensitivity to active ingredients or excipients of the investigational drugs.
- •Pregnancy, lactation, or women of childbearing potential unwilling/unable to use contraception.
- •Other conditions deemed unsuitable for participation by the investigator (e.g., compromised protocol compliance or safety risks).
研究组 & 干预措施
Induction therapy and maintenance therapy of BGR
- Induction Therapy Induction Therapy consists of zanubrutinib plus lenalidomide: each cycle lasts 28 days, up to 6 cycles, followed by maintenance therapy.
- Maintenance Therapy Maintenance therapy consists of zanubrutinib plus lenalidomide: Lenalidomide is continued for 1 year. Zanubrutinib is continued for 2 years.
干预措施: Induction Therapy (Drug)
Induction therapy and maintenance therapy of BGR
- Induction Therapy Induction Therapy consists of zanubrutinib plus lenalidomide: each cycle lasts 28 days, up to 6 cycles, followed by maintenance therapy.
- Maintenance Therapy Maintenance therapy consists of zanubrutinib plus lenalidomide: Lenalidomide is continued for 1 year. Zanubrutinib is continued for 2 years.
干预措施: Maintenance Therapy (Drug)
结局指标
主要结局
Objective response rate，ORR
时间窗: up to the end of 9 cycles of treatment(each cycle is 28 days)]
defined as the proportion of patients with complete or partial response as assessed by response to induction therapy.
次要结局
- complete response rate，CRR(Up to the end of 9 cycles of treatment(each cycle is 28 days))
- progression-free survival，PFS(up to 5 years)
- duration of response，DOR(up to 5 years)
- Overall survival，OS(Up to 5 years)
- Minimal Residual Disease，MRD(Up to the end of 2 years (each cycle is 28 days))
- Adverse event rate(Up to the end of 2 years (each cycle is 28 days))