Multicenter, Randomized, Controlled (Comparative), Open, Prospective Study Evaluating an Efficacy of R-DA-EPOCH-21, R-mNHL-BFM-90 and (Auto-SCT)in Patients With DLBCL
试验速览
- 阶段
- 3 期
- 入组人数
- 300
- 试验地点
- 1
- 主要终点
- complete response
研究概览
简要总结
Purpose: to evaluate an efficacy of chemotherapy regimens R-DA-EPOCH-21 and R-mNHL-BFM-90 with and without autologous hematopoietic stem cells transplantation (auto-SCT) in newly diagnosed patients with DLBCL with intermediate and high risk.
详细描述
Patients initially are randomized into 4 arms:
- st arm R-DA-EPOCH-21
- nd arm R-mNHL-BFM-90
- rd arm R-DA-EPOCH-21 + auto-SCT
- th arm of R-mNHL-BFM-90 + auto-SCT
Patients who achieved complete remission after 6 cycles of R-DA-EPOCH-21 or R-mNHL-BFM-90 immunochemotherapy continue to be under observation (1st and 2nd arms) or continue treatment with Rituximab + BCNU+Etoposid+Ara-C+Melphalan (R-BEAM) followed by auto-SCT (3rd and 4th arms). Patients who achieved partial remission after 6 cycles of R-DA-EPOCH-21 or R-mNHL-BFM-90 immunochemotherapy continue treatment with 2 cycles of Rituximab+Dexamethasone+Ara-C+Cisplatin (R-DHAP), continue to be under observation (1st and 2nd arms) or continue treatment with R-BEAM, followed by auto-SCT (3rd and 4th arms).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Newly diagnosed DLBCL,
- •No previous treatment with chemotherapy and/or radiation therapy of DLBCL
- •Presence of 2 or more signs of unfavorable prognosis (IPI 2-4)
- •Age 18-60 years.
排除标准
- •Transformation of mature cell lymphomas in DLBCL.
- •B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Hodgkin's lymphoma
- •B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma
- •DLBCL of central nervous system (CNS)
- •testicular DLBCL
- •Primary mediastinal large B-cell lymphoma
- •Pretreated DLBCL.
- •HIV-associated DLBCL
- •Congestive heart failure, unstable angina, severe cardiac arrhythmias and conduction disturbances, myocardial infarction.
- •Renal insufficiency (serum creatinine greater than 0.2 mmol/L) (except cases with specific kidney infiltration, urinary tract compression by tumor conglomerate or presence of uric acid nephropathy due to massive cytolysis syndrome).
- •Liver failure (except cases with liver tumor infiltration), acute hepatitis or active phase of chronic hepatitis B or C with serum bilirubin greater than 1.5 standards, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) greater than 3 standards, prothrombin index less than 70%.
- •Severe pneumonia (except cases with specific lungs infiltration), accompanied by respiratory failure (dyspnea > 30 in min., hypoxemia less than 70 mm Hg, when it is impossible to compensate situation in 2-3 days).
- •Life-threatening bleeding (gastrointestinal, intracranial), with exception of bleeding due to tumor infiltration of organs (stomach, intestines, uterus, etc.) and disseminated intravascular coagulation due to underlying disease complications after their successful conservative treatment.
- •Severe mental disorders (delusions, severe depressive syndrome and other manifestations of productive symptoms) not related with specific infiltration of central nervous system.
- •Decompensated diabetes.
研究组 & 干预措施
R-DA-EPOCH-21
Protocol involves 6 cycles.
干预措施: R-DA-EPOCH-21 (Drug)
R-DA-EPOCH-21 + auto-SCT
Protocol involves 6 cycles. Patients with complete remission undergo auto-SCT after 6 cycles and patients with partial remission after 6 cycles undergo auto-SCT after 2 cycles of R-DHAP
干预措施: R-DA-EPOCH-21 + auto-SCT (Drug)
R-mNHL-BFM-90
Course A:
Rituximab 375 mg/m2 IV 0 day, Dexamethasone 10 mg/m2/day IV 1 - 5 days, Methotrexate 1000 mg/m2 12 h IV 1 day, Ifosfamide 800 mg/m2/day 1 h IV 1 - 5 days, Etoposide 100 mg/m2/day IV 4, 5 days, Doxorubicin 25 mg/m2/day IV 1, 2 days, Vincristine 2 mg IV 1 day, Cytarabine 100 mg/m2/day IV 1 h 4, 5 days.
Course B:
Rituximab 375 mg/m2 IV 0 day, Dexamethasone 10 mg/m2/day IV 1 - 5 days, Cyclophosphamide 200 mg/m2/day IV 1 h 1 - 5 days, Methotrexate 1000 mg/m2 12 h IV 1 day, Doxorubicin 25 mg/m2/day IV 4, 5 days, Vincristine 2 mg IV 1 day. Protocol involves 6 cycles : A-B-A-B-A-B. One cycle continues 21 days.
干预措施: R-mNHL-BFM-90 (Drug)
R-mNHL-BFM-90 + auto-SCT
Protocol involves 6 cycles R-mNHL-BFM-90: A-B-A-B-A-B. Patients with complete remission undergo auto-SCT after 6 cycles and patients with partial remission after 6 cycles undergo auto-SCT after 2 cycles of R-DHAP
干预措施: R-mNHL-BFM-90 + auto-SCT (Drug)
结局指标
主要结局
complete response
时间窗: 168 day
(physical examination, standard blood tests, including assessment of LDH level, thoracic and abdominal computerized tomography (together with any other anatomic site, as clinically indicated), bone marrow biopsy in case of bone marrow involvement and 18F-fludeoxyglucose positron emission tomography (18FDG-PET) (not mandatory) in case of residual measurable disease at the end of the chemoimmunotherapy).
次要结局
- overall survival(Five-year survival)
- disease-free survival(Five-year survival)
- event-free survival(Five-year survival)
研究者
Elena N.Parovichnikova
MD, PhD
National Research Center for Hematology, Russia