Study Evaluating Relapses in Central Nervous System in Patients With Diffuse Large B-Cell Lymphoma Treated With Chemotherapy With or Without CNS Prophylaxis. Multicentric, Prospective, Randomized Phase III Study
试验速览
- 阶段
- 3 期
- 发起方
- 入组人数
- 500
- 试验地点
- 6
- 主要终点
- Cumulative incidence of CNS relapse in patients treated either with methotrexate i.v. or methotrexate i.t. or without CNS prophylaxis
研究概览
简要总结
Comparison of cumulative incidence of CNS relapses in patients with diffuse large B-cell lymphoma with intermediate or high risk of CNS relapse treated with CNS prophylaxis: either with 2 doses of intravenous methotrexate 3g/m2 i.v.(arm A) or 6 doses of intrathecal methotrexate 12mg (arm B) and in patients with low risk of CNS relapse without CNS prophylaxis (arm C).
详细描述
Patients with diffuse large B-cell lymphoma are evaluated for risk factors of CNS relapse during initial staging (age > 60years, lactate dehydrogenase (LDH) > reference range, clinical stage III/IV, performance status according to Eastern Cooperative Oncology Group (ECOG) >1, kidney and/or adrenal gland involvement, involvement > 1 extranodal organ) including evaluation of cerebrospinal fluid.
All patients with systemic DLBCL without CNS involvement are treated with systemic chemotherapy: either 6 cycles of R CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednison) +2xR (rituximab) or 6 cycles of DA EPOCH R (dose adjusted etoposide, prednison, vincristin, cyclophosphamide, doxorubicin) +2xR (rituximab). Patients with ≥ 2 risk factors for CNS relapse or with occult meningeal involvement will be randomized in 1:1 ratio either into arm A with 2 cycles of prophylactic methotrexate 3g/m2 i.v., or into arm B with prophylactic 6x intrathecal methotrexate 12mg (1x intrathecal methotrexate in each cycle of systemic chemotherapy). Patients with 0-1 risk factor will be allocated into arm C without CNS prophylaxis. Patients will be observed for CNS relapse during the follow-up of 1year after the end of the first-line treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 72 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •histologically confirmed DLBCL
- •age 18-72 years
- •signed informed consent with the study
- •first-line treatment 6 cycles of R CHOP +2x R or 6 cycles of DA EPOCH R+ 2xR
排除标准
- •DLBCL and concomitant initial CNS involvement
- •PMBL (primary mediastinal B-cell lymphoma)
- •treatment with another chemotherapy than R CHOP or DA EPOCH R
- •HIV positive, or active hepatitis B or C
- •other concomitant serious disease (based on the decision of the physician-investigator)
- •non-compliance of a patient
- •any contraindication for application of anthracycline based chemotherapy or high dose methotrexate
- •pregnancy or breast-feeding
研究组 & 干预措施
Arm A - Methotrexate i.v.
Patients with risk factors for CNS relapse ≥ 2 or with occult meningeal involvement will receive 2 cycles of methotrexate 3g/m2 i.v. after the 3rd and 6th cycle of systemic chemotherapy (R CHOP or DA EPOCH R).
干预措施: Methotrexate (Drug)
Arm B - Methotrexate i.t.
Patients with risk factors for CNS relapse ≥ 2 or with occult meningeal involvement will receive intrathecal methotrexate 12mg in each cycle of systemic chemotherapy (6x).
干预措施: Methotrexate (Drug)
结局指标
主要结局
Cumulative incidence of CNS relapse in patients treated either with methotrexate i.v. or methotrexate i.t. or without CNS prophylaxis
时间窗: 1 year
次要结局
- Overall response rate(1 year)
- Overall survival(2 years)
- Progression-free survival(2 years)
- Complete remission rate(1 year)