Phase II Clinical Study of Zanubrutinib Combined With Bendamustine and Rituximab (ZBR) for Time-limited Treatment of Waldenstrom Macroglobulinemia
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Best combined complete response (CR) and very good partial response (VGPR)
研究概览
简要总结
This study aims to evaluate the long-term efficacy of BTK inhibitor Zanubrutinib combined bendamustine and rituximab (ZBR) for time-limited treatment of Waldenstrom macroglobulinemia, The combination therapy is expected to improve the remission depth, prolong the remission time, and improve the progression-free survival and overall survival of newly diagnosed WM patients. On the one hand, the patients have to bear a long-term economic burden, which is often difficult for some patients to adhere to for a long time. On the other hand, in the course of long-term treatment of BTKi, drug resistance and intolerable side effects are prone to occur. At the same time, it can prevent the disease rebound after the withdrawal of BTKi, so as to achieve the phased withdrawal of WM
详细描述
WM not only has the characteristics of lymphoma, such as lymphadenopathy, hepatosplenomegaly, and tumor cells expressing CD20, but also has the characteristics of myeloma, such as secreting monoclonal IgM, and tumor cells expressing plasma cell differentiation marker CD38, etc. Clinical studies have also shown that BR regimen and BTK inhibitor zanubrutinib are effective for WM.
This study aims to evaluate the long-term efficacy of BTK inhibitor Zanubrutinib combined bendamustine and rituximab (ZBR) for time-limited treatment of Waldenstrom macroglobulinemia, The combination therapy is expected to improve the remission depth, prolong the remission time, and improve the progression-free survival and overall survival of newly diagnosed WM patients. On the one hand, the patients have to bear a long-term economic burden, which is often difficult for some patients to adhere to for a long time. On the other hand, in the course of long-term treatment of BTKi, drug resistance and intolerable side effects are prone to occur. At the same time, it can prevent the disease rebound after the withdrawal of BTKi, so as to achieve the phased withdrawal of WM. This prospective phase II study was designed to evaluate the rate of deep response in newly diagnosed symptomatic WM. Eligible patients received ZBR for 6 cycles followed by zanubrutinib monotherapy for an additional 6 months.
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
- •The gender of the patient is not limited, and the age is ≥18 years old;
- •Must meet WM's diagnostic standards;
- •The patient is an untreated or patient who has not undergone standard treatment.
- •The specific conditions are as follows:
- •No combined chemotherapy with BTKi, BR, RCD, VRD, CHOP and COP
- •No treatment regimen containing fludarabine
- •Chlorambucil or cyclophosphamide for less than 4 weeks (alone or in combination with adrenal glucocorticoids)
- •The above treatment did not reach the treatment response (MR)
- •If the above treatment has been applied, the treatment needs to be stopped for 2 weeks before entering the group to start treatment
- •The indications for the treatment of indolent lymphoma mainly include (at least one of the following conditions):
- •Symptomatic hyperviscosity;
- •Symptomatic peripheral neuropathy;
- •Amyloidosis;
- •Cold agglutinin disease; cryoglobulinemia;
- •Disease-related cytopenia (Hb<100 g/L, PLT<100×10^9/L);
- •Giant lymph nodes;
- •Those with systemic systemic symptoms: for two weeks/recurrent fever (above 38℃) and not caused by infection, or Night sweats and/or weight loss >10% within 6 months;
- •The disease progresses rapidly, for example, the lymph nodes increase by more than 50% within 2 months, and/or peripheral blood lymphocytes absolute value doubling time <6 months, and/or rapid hemoglobin or platelet non-autoimmune causes slow down
- •When there is evidence that the disease has transformed.
- •ECOG score ≤ 2 points
- •Laboratory examination: neutrophils ≥ 0.75×10^9/L; platelets ≥ 50×10^9/L; total bilirubin ≤ 2.5 times upper limit; alanine aminotransferase/aspartate aminotransferase ≤3 times upper limit. Creatinine clearance rate ≥ 30ml/min.
- •The patient's expected survival time is ≥ 3 months.
排除标准
- •Malignant tumors (including active central nervous system lymphoma) other than B-NHL have been diagnosed or treated within the past year;
- •There is clinical evidence that large cell lymphoma transformation has occurred;
- •Non-lymphoma-related liver and kidney damage: alanine aminotransferase (ALT)> 3 times the upper limit of normal value, aspartate aminotransferase (AST)> 3 times the upper limit of normal value, total bilirubin (TBIL)> upper limit of normal value 2 Times, serum creatinine clearance rate <30ml/min;
- •Other serious medical conditions will affect the study (such as uncontrolled diabetes, gastric ulcers, other serious cardiopulmonary diseases, etc.). The decision-making power belongs to the researcher;
- •Known history of infection with human immunodeficiency virus (HIV) or active hepatitis B virus (HBV) infection, or any uncontrolled active systemic infection requiring intravenous antibiotics.
- •Central nervous system dysfunction with clinical manifestations or central invasion (Bing-Neel syndrome);
- •Patients who have undergone major surgery (not including lymph node biopsy) within the past 14 days or expected major surgery during treatment;
- •Inability to swallow capsules or suffer from malabsorption syndrome, diseases that significantly affect gastrointestinal function, have undergone gastric or small bowel resection, symptomatic inflammatory bowel disease or ulcerative colitis, partial or complete intestinal obstruction.
- •Need to receive strong cytochrome P450 (CYP) 3A inhibitor treatment.
- •Women who are pregnant or breastfeeding, women of childbearing age who have not taken contraception;
- •Allergy to the drugs used.
研究组 & 干预措施
Zanubrutinib, bendamustine, rituximab combination therapy Group
Patients were treated with ZBR regimen for 6 cycles, followed by zanubrutinib monotherapy for an additional 6 months.
干预措施: Zanubrutinib, Bendamustine and Rituximab (Drug)
结局指标
主要结局
Best combined complete response (CR) and very good partial response (VGPR)
时间窗: up to the end of 12 cycles of treatment(each cycle is 28 days)
To evaluate the efficacy of zanubrutinib plus bendamustine and rituximab (ZBR) regimen in the treatment of newly diagnosed WM patients, mainly the best deep response rate, namely the best deep response rate (VGPR and above).
次要结局
- Progression free survival(PFS)(Up to 3 years after the end of treatment)
- Overall objective response rate (ORR), complete response rate(CR),major response rate(MR)(up to the end of 12 cycles of treatment(each cycle is 28 days))
- Safety of treatment regimens(Up to 3 years after the end of treatment)
- Overall survival(OS)(Up to 3 years after the end of treatment)
- Time to response, time to best response(up to the end of 12 cycles of treatment(each cycle is 28 days))
- Time to Next Treatment(Up to 3 years after the end of treatment)
- Duration of Response(Up to 3 years after the end of treatment)