An Randomized, Open-label, Phase III Study Comparing Thalidomide Combined With R-CHOP and R-CHOP in Newly Diagnosed Double-expressor Diffuse Large B-Cell Lymphoma Patients
试验速览
- 阶段
- 3 期
- 入组人数
- 162
- 试验地点
- 1
- 主要终点
- 3 year PFS
研究概览
简要总结
The purpose of this study is to evaluate the efficacy of Thalidomide combined with R-CHOP(RT-CHOP) in newly diagnosed，untreated double-expressor Diffuse Large B-Cell Lymphoma patients (DLBCL)
详细描述
Double expressor lymphoma is a subtype of diffuse large B-cell lymphoma defined as having increased expression of MYC and BCL-2 and/or BCL-6 by immunohistochemistry. Patients with double-expressor lymphomas have a poor prognosis when treated with standard chemoimmunotherapy and have increased risk of progression and recurrence. The investigators conducted this study to evaluate the efficacy of Thalidomide combined with R-CHOP(RT-CHOP) in newly diagnosed double-expressed, untreated Diffuse Large B-Cell Lymphoma patients (DLBCL). Thalidomide is a kind of glutamate derivatives, which can inhibit angiogenesis by blocking bFGF and VEGF, and it can also modulate the immune system by co-stimulating T cell proliferation. In addition, thalidomide can also inhibit the IKK activity and block the activation of NF-kB. In this open-label, randomized, phase III study, we are aiming to compare Thalidomide combined with R-CHOP(RT-CHOP) and R-CHOP in newly diagnosed double-expressor Diffuse Large B-Cell Lymphoma patients (DLBCL), in order to find a potential promising way to treat this subtype of lymphoma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Age range ≥18 years old
- •Eastern Cooperative Oncology Group performance status 0 to 2;
- •Newly diagnosed, untreated, histological confirmed diffuse large B cell lymphoma, non-GCB subtype, and Myc≥40% as well as Bcl-2≥70% through immunohistochemistry；
- •Measurable disease was defined as at least one lesion ≥1.5 cm in length-diameter and ≥0.5 cm in short-diameter by CT.
- •Patients have written informed consent to participate in the study.
- •Ultrasonic cardiogram showed left ventricle ejection fraction ≥ 50%, EKG showed on signs of myocardial ischemia, with no previous arrhythmia which need pharmacological intervention.
- •White blood cell ≥ 3.5×109/L, absolute neutrophil count ≥ 1.5×109/L，platelet ≥ 80×109/L，hemoglobin ≥ 90 g/L
- •total bilirubin < 1.5×upper limit of normal(ULN), ALT and AST < 1.5× ULN
- •serum creatine <1.5×ULN, and creatinine clearance rate (CCR) ≥ 30 ml/min
排除标准
- •Presence of CNS involvement
- •Particular kind of DLBCL，such as primary mediastinal/thymic B-cell lymphoma, elderly EBV positive DLBCL, primary cutaneous large B lymphoma.
- •History of myocardial diseases, such as congenital heart disease, pericardial disease, heart failure, myocardial infarction, coronary heart disease, valvular heart disease, myocardosis, arrhythmia.
- •History of severe chronic cutaneous diseases.
- •History of allergic asthma or severe allergic diseases.
- •Uncontrolled hypertension and diabetes.
- •History of other malignancies except cured basal cell carcinoma of skin and carcinoma in-situ of uterine cervix
- •HIV, HCV, or syphilis infection；
- •Presence of active HBV infection（HBV-DNA≥104）；
- •Pregnant or lactating women
- •Previously received organ transplant
- •Having usage of Thalidomide；
- •History of deep vein thrombosis
- •Serious uncontrolled infection
- •Having contraindications to the use of large doses of hormone, such as uncontrolled hyperglycemia, gastric ulcer, mental disorder.
- •Severe neurol of mental illness, including dementia and epilepsy.
研究组 & 干预措施
Thalidomide combined with R-CHOP
rituximab 375 mg/m2,ivgtt D1 cyclophosphamide 750 mg/m2 iv D2 vincristine 1.4 mg/m2 [capped at 2.0 mg], iv D2 doxorubicin 50 mg/m2 iv D2 prednisone 100 mg/m2 per day PO D2-6 Thalidomide 200mg PO QN D1-21
干预措施: Thalidomide combined with R-CHOP (Drug)
R-CHOP
rituximab 375 mg/m2,ivgtt D1 cyclophosphamide 750 mg/m2 iv D2 vincristine 1.4 mg/m2 [capped at 2.0 mg], iv D2 doxorubicin 50 mg/m2 iv D2 prednisone 100 mg/m2 per day PO D2-6
干预措施: R-CHOP (Drug)
结局指标
主要结局
3 year PFS
时间窗: 3 years
3 year progression free survival
次要结局
- ORR(6 weeks，12 weeks，18weeks)
- OS(3 years)
- adverse event(throughout the treatment period，up to 6 months)
研究者
Fangfang Lv, MD
principle investigator
Fudan University