Prospective, Multicenter, Randomized ,Open-labeled, Phase III Study Comparing High-dose Intravenous Methotrexate Versus Intrathecal Methotrexate for the Prophylaxis of Central Nervous System Relapse in Diffuse Large B Cell Lymphoma
试验速览
- 阶段
- 3 期
- 入组人数
- 205
- 试验地点
- 1
- 主要终点
- Cumulative incidence of CNS relapse
研究概览
简要总结
The outcome of patients with central nervous system (CNS) relapse in DLBCL is poor, with median survival times of 2-5 months. This fatal prognosis necessitates CNS prevention in a subgroup of patients with a high risk of CNS relapse.
Intrathecal methotrexate (ITMTX) has traditionally been used, although its efficacy for CNS prophylaxis is contradictory. High-dose intravenous methotrexate (IVMTX) has been suggested as an alternative approach. Considering the lack of evidence supporting the role of ITMTX, the investigators propose to compare the efficacy of ITMTX and IVMTX for prophylaxis of CNS relapse in a subgroup of patients with DLBCL at a high risk for CNS relapse.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged ≥18 years <80
- •Newly diagnosed, histologically confirmed DLBCL
- •High-risk of CNS recurrence at diagnosis:
- •Age-adjusted IPI (aaIPI) ≥2 or IPI ≥4 with extranodal involvement of >1 site plus serum lactate dehydrogenase (LDH) > normal OR
- •Involvement of high-risk locations: bone marrow, nasal or paranasal sinuses, testis, epidural disease (paravertebral or vertebra), breast, adrenal or kidney
- •Estimated life expectancy of more than 90 days
- •Performance status (ECOG) ≤ 2
- •Written informed consent
排除标准
- •Psychiatric or mental disorder which make the patient unable to give an informed consent and/or adhere to the protocol
- •DLBCL or following subtypes:
- •Primary mediastinal large B-cell lymphoma
- •Grey zone lymphoma)
- •Primary cutaneous DLBCL
- •Previous immunochemotherapeutic treatment for DLBCL other than short-term use of corticosteroids (≤ 8 days before randomization)
- •Previous radiotherapy
- •CNS involvement of DLBCL at diagnosis
- •HIV positive
- •Any contraindication for application of RCHOP or high dose methotrexate
- •Any of following laboratory results
- •Absolute neutrophil count < 1,500 cells/mm3 (1.5 x 109/L),
- •Platelet count < 100,000/mm3 (100 x 109/L), or < 75,000 /mm3 in patients with bone marrow involvement,
- •Serum aspartate transaminase or serum alanine transaminase ≥3.0 x upper limit of normal (ULN),
- •Serum total bilirubin > 2 x ULN (with the exception of hemolytic anemia),
- •Serum creatinine >2.0 x ULN or creatinine clearance <50 mL/min
- •Active cancer except curable basal cell carcinoma, cervical cancer in situ, and/or papillary thyroid cancer during the last five years
- •Ejection fraction < 45% on echocardiography
- •Uncontrolled active hepatitis
- •Pregnancy or breast-feeding
- •Men and women of reproductive potential no agreeing to use an acceptable method of birth control during treatment
研究组 & 干预措施
High-dose Intravenous Methotrexate
干预措施: High-dose intravenous methotrexate (Drug)
Intrathecal Methotrexate
干预措施: Intrathecal methotrexate (Drug)
结局指标
主要结局
Cumulative incidence of CNS relapse
时间窗: 2 year
The rate of relapse will be analyzed by the cumulative incidence method
次要结局
- Toxicity(2 year)
- Progression-free survival (PFS)(2 year)
研究者
Deok-Hwan Yang
Principal Investigator
Chonnam National University Hospital