Rituximab, Cyclophosphamide, Vincristine, and Prednisone in Combination With Doxorubicin (R-CHOP) Versus in Combination With Pegylated-liposomal Doxorubicin (R-CDOP) as First-line Treatment for Elderly Patients With Diffuse Large-B-cell Lymphoma: a Randomised, Multicentre, Non-inferiority Study
试验速览
- 阶段
- 3 期
- 发起方
- 入组人数
- 216
- 试验地点
- 7
- 主要终点
- event-free survival (EFS)
研究概览
简要总结
The combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP regimen) has been the first-line chemotherapy for elderly patients with diffuse large B-cell lymphoma (DLBCL). The treatment-related toxicities, especially the severe cardiac toxicities induced by anthracycline drugs (doxorubicin), have become a major concern among elderly patients. Pegylated liposomal doxorubicin is a formulation of doxorubicin with a prolonged circulation time and unique toxicity profile. Previous single arm studies of elderly patients with lymphoma used pegylated liposomal doxorubicin instead of traditional doxorubicin in combination with rituximab, cyclophosphamide, vincristine, and prednisone (the novel R-CDOP regimen), and demonstrated better safety profile, including less bone marrow suppression and less cardiac toxicities, while maintaining the efficacy. However, the efficacy and safety of these two regimens (R-CHOP and R-CDOP) have not been head-to-head compared in a randomized study. The aim of this study is to compare the efficacy and safety of R-CDOP (rituximab, cyclophosphamide, pegylated liposomal doxorubicin, vincristine, and prednisone) and R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in previously untreated elderly patients with DLBCL.
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
- 60 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Pathologically confirmed diagnosis of CD20-positive diffuse large B-cell lymphoma
- •60~80 years old
- •Ann Arbor stage I~IV
- •ECOG physical score of 0~2
- •Have not received previous treatment to lymphoma, including chemotherapy, radiotherapy, or biotherapy
- •Have at least one clinically measurable lesion: >= 2cm under physical examination, or >= 1.5cm under computed tomography (CT) or magnetic resonance (MR)
- •Life expectancy of >= 3 months
- •Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase and total bilirubin <= 2 × upper limit of normal (ULN)
- •Glomerular filtration rate (MDRD method) >= 30ml/min
- •No abnormalities in blood coagulative function
- •Generally normal bone marrow function: while blood cell >= 3,000/μL, absolute neutrophil count >= 1,500/μL, hemoglobin >= 100g/L, platelet >= 75,000/μL
- •No evidence of active hepatitis B or C virus, or human immunodeficiency virus infection
- •Left ventricular ejection fraction (LVEF) >= 45% measured by two dimensional echocardiography or multi-gated acquisition (MUGA) scan
- •Cardiac function of class I-II in New York Heart Association (NYHA) classification
排除标准
- •Patients with indolent lymphoma
- •Positive results for in situ hybridization for Epstein-Barr virus encoded RNA (EBER)
- •Serum Epstein-Barr virus DNA >= 1,000 copies/ml
- •Double-hit lymphoma confirmed by fluorescence in situ hybridization (FISH)
- •Primary mediastinal B-cell lymphoma
- •Involvement of central nervous system
- •Bulky disease (>= 10cm)
- •History of cardiac disease, including clinically significant ventricular tachycardia, atrial fibrillation, conduction block, myocardial infarction within 1 year, congestive heart failure, symptomatic coronary heart disease which needs medication
- •Known allergic reaction to any component of the agents used in the chemotherapeutic regimens that are used in the study
- •Previous exposure to anthracycline drugs, rituximab, or chemotherapy for lymphoma
- •History of malignant carcinoma within 5 years (except carcinoma in situ of the skin and uterine cervix, and prostatic carcinoma)
- •Currently enrolled in other clinical studies
- •Other conditions that the investigators consider as inappropriate for enrolling into this study
研究组 & 干预措施
R-CHOP
This group received R-CHOP regimen as the first-line chemotherapy. Rituximab, 375mg/m2, iv, d0; Cyclophophamide, 750mg/m2, iv, d1; Doxorubicin, 50mg/m2, iv, d1; Vincristine, 2mg/m2 (max 2mg), iv, d1; Prednisone, 100mg, po, d1-5. Repeat every 21 days for 6-8 cycles or until the criteria of terminating treatment was met.
干预措施: Doxorubicin (Drug)
R-CHOP
This group received R-CHOP regimen as the first-line chemotherapy. Rituximab, 375mg/m2, iv, d0; Cyclophophamide, 750mg/m2, iv, d1; Doxorubicin, 50mg/m2, iv, d1; Vincristine, 2mg/m2 (max 2mg), iv, d1; Prednisone, 100mg, po, d1-5. Repeat every 21 days for 6-8 cycles or until the criteria of terminating treatment was met.
干预措施: Rituximab (Drug)
R-CHOP
This group received R-CHOP regimen as the first-line chemotherapy. Rituximab, 375mg/m2, iv, d0; Cyclophophamide, 750mg/m2, iv, d1; Doxorubicin, 50mg/m2, iv, d1; Vincristine, 2mg/m2 (max 2mg), iv, d1; Prednisone, 100mg, po, d1-5. Repeat every 21 days for 6-8 cycles or until the criteria of terminating treatment was met.
干预措施: Cyclophophamide (Drug)
R-CHOP
This group received R-CHOP regimen as the first-line chemotherapy. Rituximab, 375mg/m2, iv, d0; Cyclophophamide, 750mg/m2, iv, d1; Doxorubicin, 50mg/m2, iv, d1; Vincristine, 2mg/m2 (max 2mg), iv, d1; Prednisone, 100mg, po, d1-5. Repeat every 21 days for 6-8 cycles or until the criteria of terminating treatment was met.
干预措施: Vincristine (Drug)
R-CHOP
This group received R-CHOP regimen as the first-line chemotherapy. Rituximab, 375mg/m2, iv, d0; Cyclophophamide, 750mg/m2, iv, d1; Doxorubicin, 50mg/m2, iv, d1; Vincristine, 2mg/m2 (max 2mg), iv, d1; Prednisone, 100mg, po, d1-5. Repeat every 21 days for 6-8 cycles or until the criteria of terminating treatment was met.
干预措施: Prednisone (Drug)
R-CDOP
This group received R-CDOP regimen as the first-line chemotherapy. Rituximab, 375mg/m2, iv, d0; Cyclophophamide, 750mg/m2, iv, d1; Pegylated liposomal doxorubicin, 30mg/m2, iv, d1; Vincristine, 2mg/m2 (max 2mg), iv, d1; Prednisone, 100mg, po, d1-5. Repeat every 21 days for 6-8 cycles or until the criteria of terminating treatment was met.
干预措施: Pegylated liposomal doxorubicin (Drug)
R-CDOP
This group received R-CDOP regimen as the first-line chemotherapy. Rituximab, 375mg/m2, iv, d0; Cyclophophamide, 750mg/m2, iv, d1; Pegylated liposomal doxorubicin, 30mg/m2, iv, d1; Vincristine, 2mg/m2 (max 2mg), iv, d1; Prednisone, 100mg, po, d1-5. Repeat every 21 days for 6-8 cycles or until the criteria of terminating treatment was met.
干预措施: Rituximab (Drug)
R-CDOP
This group received R-CDOP regimen as the first-line chemotherapy. Rituximab, 375mg/m2, iv, d0; Cyclophophamide, 750mg/m2, iv, d1; Pegylated liposomal doxorubicin, 30mg/m2, iv, d1; Vincristine, 2mg/m2 (max 2mg), iv, d1; Prednisone, 100mg, po, d1-5. Repeat every 21 days for 6-8 cycles or until the criteria of terminating treatment was met.
干预措施: Cyclophophamide (Drug)
R-CDOP
This group received R-CDOP regimen as the first-line chemotherapy. Rituximab, 375mg/m2, iv, d0; Cyclophophamide, 750mg/m2, iv, d1; Pegylated liposomal doxorubicin, 30mg/m2, iv, d1; Vincristine, 2mg/m2 (max 2mg), iv, d1; Prednisone, 100mg, po, d1-5. Repeat every 21 days for 6-8 cycles or until the criteria of terminating treatment was met.
干预措施: Vincristine (Drug)
R-CDOP
This group received R-CDOP regimen as the first-line chemotherapy. Rituximab, 375mg/m2, iv, d0; Cyclophophamide, 750mg/m2, iv, d1; Pegylated liposomal doxorubicin, 30mg/m2, iv, d1; Vincristine, 2mg/m2 (max 2mg), iv, d1; Prednisone, 100mg, po, d1-5. Repeat every 21 days for 6-8 cycles or until the criteria of terminating treatment was met.
干预措施: Prednisone (Drug)
结局指标
主要结局
event-free survival (EFS)
时间窗: two year
Defined as time from the date of randomization to the date of disease progression, death due to any cause, termination of treatment, or the most recent follow-up
次要结局
- overall response rate (ORR)(at week 6, 12, 18, and 24 after randomization)
- complete remission (CR) rate(at week 6, 12, 18, and 24 after randomization)
- overall survival (OS)(two year)
研究者
Wenqi Jiang
Chief of Department of Internal Medicine, Sun Yat-sen University Cancer Center
Sun Yat-sen University