Incidence of Hepatitis B Reactivation in Non-Hodgkin's Lymphoma Patients Who Receive Rituximab-containing Chemotherapy and Are Previously Infected With Hepatitis B Virus
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 202
- 试验地点
- 1
- 主要终点
- enroll 150 patients
研究概览
简要总结
This is a single-arm study. Key eligibility criteria include (1) newly diagnosed, diffuse large B-cell or follicular cell non-Hodgkin's lymphoma; (2) negative test for hepatitis B surface antigen (HBsAg) and positive for antibody to hepatitis B core antigen (anti-HBc); (3) adequate bone marrow, liver, and kidney function. All eligible patients will receive rituximab-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) chemotherapy according to current treatment guidelines. The primary endpoint of this study is the incidence of hepatitis B virus (HBV) reactivation, defined by a greater than 10-fold increase, compared with previous nadir levels, of HBV DNA during rituximab-CHOP chemotherapy and within 1 year after completion of the last course of rituximab-CHOP chemotherapy. Patients who have HBV reactivation during the study period will receive free entecavir treatment, one of the standard treatment for chronic hepatitis B, for 48 weeks. The secondary endpoints include the incidence of hepatitis flare, defined as a greater than 3 fold increase of serum alanine aminotransferase (ALT) level that exceeded 100 IU/L, and the efficacy and safety of rituximab-CHOP chemotherapy.
In the T1408 study we enrolled patients with newly diagnosed lymphoma who were HBsAg (-) and anti-HBc (+) and were to receive rituximab-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone)-based chemotherapy. Key findings of this study included (1) HBV reactivation, defined as a greater than 10-fold increase in HBV DNA compared with previous nadir levels, occurred to 10-20% of patients, depending on the sensitivity of the HBV DNA tests; (2) no HBV-related death with the prompt anti-viral therapy upon HBV reactivation; (3) patients with HBV reactivation were associated with poorer progression-free survival and overall survival; (4) serological breakthrough (i.e., re-appearance of HBsAg) is an important predictor of HBV-related hepatitis flare.
In this amendment we will enroll more patients to clarify the above findings: (1) the association between HBV reactivation and survival; (2) diagnostic value of quantitative HBsAg and anti HBc tests on HBV reactivation; (3) whether host factors (DNA polymorphism) may help predict HBV reactivation. A larger patient cohort is needed to identify (1) baseline features that may help predict HBV reactivation, and (2) on-treatment features that may help timely anti-viral therapy.
详细描述
Treatment plan:
A typical course of rituximab-CHOP chemotherapy is as follows:
rituximab 375 mg/m2 i.v., day 1, cyclophosphamide 750 mg/m2 i.v., day 1, doxorubicin 50 mg/m2 i.v., day 1, vincristine 1.4 mg/m2 (maximal 2 mg) i.v., day 1, prednisolone 40 mg/m2/day p.o., day 1 to day 5.
Typically the treatment will be repeated every 3 weeks. If the patients cannot recover from chemotherapy-induced toxicity at the schedule time of the next course of treatment, modification of chemotherapy dosage or delay of chemotherapy administration will be done according to local treatment standard and will be recorded.
The use of component therapy or granulocyte colony-stimulating factor will be at the discretion of individual investigator.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically proven diffuse large B-cell or follicular B-cell non-Hodgkin's lymphoma, for which chemotherapy with rituximab-CHOP chemotherapy is considered treatment-of-choice.
- •Evidence of 'resolved' HBV infection. Eligible subjects must be negative for serum HBV surface antigen (HBsAg) and positive for anti-core antibody (anti-HBc).
- •Age >18 years.
- •Performance status with ECOG score 0-
- •No previous chemotherapy and radiotherapy, no concurrent glucocorticoid use.
- •Absolute neutrophil count (ANC) > 1,500/mm3, platelet > 100,000/mm3 in the peripheral blood.
- •Total bilirubin < 2.5 mg/dl. Alanine aminotransferase (ALT) < 3 times UNL (upper limits of normal range).
- •Serum creatinine < 1.5 mg/dl. 9.10.Life expectancy 3 months.
- •11.Signed informed consent.
排除标准
- •Pregnant or breast-feeding women.
- •Patients with history of brain metastasis or CNS involvement.
- •Child's class B or C in patients with liver cirrhosis.
- •Impaired cardiac function with NYHA (New York Heart Association) classification Gr II.
- •History of other liver diseases such as hepatitis C, D, autoimmune hepatitis, primary biliary cirrhosis, Wilsons' disease.
- •Other major systemic disease, such as active infection, significant cardiac disease, neurological deficit or psychiatric disorder, that the investigators consider to be significant risk.
- •Any concomitant cancer treatment.
- •Known hypersensitivity of any of the study drugs (rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisolone).
- •Known human immunodeficiency virus (HIV) infection.
研究组 & 干预措施
entecavir
All eligible patients will receive rituximab-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) chemotherapy according to current treatment guidelines.
干预措施: entecavir (Drug)
结局指标
主要结局
enroll 150 patients
时间窗: 3 years
次要结局
未报告次要终点