Efficacy and Safety of Ibrutinib in Patients With Chronic Lymphocytic Leukemia and Other Indolent B-cell Lymphomas Who Are Chronic Hepatitis B Virus Carriers or Occult Hepatitis B Virus Carriers
试验速览
- 阶段
- 3 期
- 入组人数
- 62
- 试验地点
- 1
- 主要终点
- Overall response rate (ORR)
研究概览
简要总结
Efficacy and Safety of ibrutinib in patients with chronic lymphocytic leukemia and other indolent B-cell lymphomas who are chronic hepatitis B virus carriers or occult hepatitis B virus carriers
详细描述
Ibrutinib is a selective oral Burton tyrosine kinase inhibitor. Through interfering with the downstream pathways of B-cell receptor signaling, it inhibits proliferation and induces apoptosis in many B-cell lymphoid malignancies. The clinical benefit of ibrutinib has been demonstrated in patients with relapsed/refractory chronic lymphocytic leukaemia, mantle cell lymphoma, small lymphocytic lymphoma, and other indolent B-cell non-Hodgkin lymphomas.
The pivotal trials of ibrutinib excluded HBsAg+ patients. Therefore, the effects of ibrutinib on HBsAg+ and anti-HBc+ patients remain entirely undefined. In view of the B-cell signaling inhibitory activity of ibrutinib, which might be more potent than rituximab in suppressing B-cells, HBV reactivation in patients exposed previously to HBV infection, including chronic HBV carriers and occult HBV carriers, could be a major clinical problem.
To enable ibrutinib to be prescribed in Asia and other regions of the world where HBV is endemic, evidence-based recommendations on prevention of HBV reactivation in at-risk populations, including chronic HBV carriers (HBsAg+), and occult HBV carriers (HBsAg- but anti-HBc+), are urgently needed.
The following treatment regimens will be adopted. Relapsed / refractory chronic lymphocytic leukemia and Waldenstrom macroglobulinaemia (lymphoplasmacytic lymphoma): 420 mg daily.
Relapsed / refractory mantle cell lymphoma: 560 mg daily. Relapsed / refractory indolent B-cell non-Hodgkin lymphoma: 560 mg daily. Treatment is continued until disease progression.
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
- •Adult patients between age of 18 - 80 years
- •Patients with indolent B-cell lymphoproliferative neoplasms that have relapsed or are refractory after at least one standard line of therapy that contains rituximab
- •Pathologically proven B-cell lymphoproliferative neoplasms including chronic lymphocytic leukaemia/small lymphocytic lymphoma, mantle cell lymphoma, marginal-zone B-cell lymphoma, and Waldenstrom macroglobulinaemia (lymphoplasmacytic lymphoma).
- •Pathologically proven follicular lymphoma, with relapse or disease progression > 12 months after previous rituximab therapy.
- •Chronic HBV carriers (HBsAg+)
- •Occult HBV carriers (HBsAg-, anti-HBc+ and HBV DNA-)
- •Haematology values within the following limits:
- •Absolute neutrophil count (ANC)1000/mm3 independent of growth factor support
- •Platelets 100,000/mm3, or 50,000/mm3 if bone marrow is involved, and independent of transfusion support in either situation
- •Biochemical values within the following limits:
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2 x upper limit of normal (ULN)
- •Total bilirubin ≤ 1.5 x ULN unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin
- •Serum creatinine ≤ 2 x ULN or estimated Glomerular Filtration Rate (Cockcroft Gault) ≥ 40 mL/min/1.73m2
- •Competent to give an informed consent
排除标准
- •Concomitant chronic liver diseases not related to HBV
- •Known history of drug-induced liver injury, chronic active hepatitis C infection, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, on-going extra-hepatic obstruction caused by cholelithiasis, cirrhosis of the liver and portal hypertension
- •Known history of drug induced pneumonitis
- •Known history of inflammatory bowel disease
- •Woman who are pregnant or breast-feeding
- •Patients who do not consent to the use of effective contraception during the study
- •Active infections.
- •Evidence of ongoing active HBV hepatitis (ALT and/or AST > 2x upper limit of normal, and detectable HBV DNA)
- •Patients known to have histological transformation of CLL to an aggressive lymphoma
- •Vaccinated with live, attenuated vaccines within 4 weeks of enrolment
研究组 & 干预措施
Ibrutinib
Relapsed / refractory chronic lymphocytic leukemia and Waldenstrom macroglobulinaemia (lymphoplasmacytic lymphoma): 420 mg daily Relapsed / refractory mantle cell lymphoma: 560 mg daily Relapsed / refractory indolent B-cell non-Hodgkin lymphoma: 560 mg daily Treatment is continued until disease progression
干预措施: Ibrutinib (Drug)
结局指标
主要结局
Overall response rate (ORR)
时间窗: 2 years
proportion of patients achieving CR or partial remission (PR)
Duration of remission
时间窗: two year
Rates of HBV Reactivation while on Ibrutinib therapy
时间窗: two year
Adverse events and severe adverse events
时间窗: two year
Incidence of AE and SAE by severity grading as assessed according to CTCAE v4.03
次要结局
未报告次要终点
研究者
Professor Yok-lam Kwong
Chair Professor
The University of Hong Kong