Randomized Study Comparing an Immuno-Chemotherapy With 6 Cycles of the Monoclonal Anti-CD20 Antibody Rituximab in Combination With 6 Cycles of Chemotherapy With CHOP ( Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone) at 21-day Intervals or 14-day Intervals, Both With or Without Consolidating Radiotherapy or Large Tumour Masses (≥7.5 cm) and/or Extranodal Involvement in Patients With Aggressive CD20 B-Cell Lymphoma Aged 18 to 60 Years With Age-Adjusted IPI=1 (All) or IPI=0 With a Large Tumour Mass (≥7.5 cm) [UNFOLDER 21/14 Study]
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 700
- 试验地点
- 152
- 主要终点
- 3 Years Event-free Survival
研究概览
简要总结
RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill cancer cells. Giving rituximab and combination chemotherapy together with radiation therapy may kill more cancer cells. It is not yet known which schedule of rituximab and combination chemotherapy is more effective when given with or without radiation therapy in treating non-Hodgkin's lymphoma.
PURPOSE: This randomized phase III trial is studying two different schedules of rituximab and combination chemotherapy with or without radiation therapy to compare how well they work in treating patients with aggressive B-cell non-Hodgkin's lymphoma.
详细描述
OBJECTIVES:
Primary
- Compare the time to treatment failure in patients with previously untreated, low-risk, aggressive, B-cell non-Hodgkin's lymphoma treated with 2 different schedules of immunochemotherapy comprising rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone with vs without radiotherapy.
Secondary
- Compare the time to progression in patients treated with these regimens.
- Compare the overall and disease-free/relapse-free survival of patients treated with these regimens.
- Compare the complete response rate in patients treated with these regimens.
- Compare the tumor control in patients treated with these regimens.
- Compare the safety of these regimens in these patients.
- Compare the pharmacoeconomics of these regimens.
- Compare patient adherence to these regimens.
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 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Interventional: 6 R-CHOP-21
Arm I (R-CHOP-21): Patients receive R-CHOP immunochemotherapy comprising rituximab IV, cyclophosphamide IV over 15 minutes, doxorubicin IV, and vincristine IV on day 1 and oral prednisone once daily on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: rituximab (Biological)
Interventional: 6 R-CHOP-21
Arm I (R-CHOP-21): Patients receive R-CHOP immunochemotherapy comprising rituximab IV, cyclophosphamide IV over 15 minutes, doxorubicin IV, and vincristine IV on day 1 and oral prednisone once daily on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: cyclophosphamide (Drug)
Interventional: 6 R-CHOP-21
Arm I (R-CHOP-21): Patients receive R-CHOP immunochemotherapy comprising rituximab IV, cyclophosphamide IV over 15 minutes, doxorubicin IV, and vincristine IV on day 1 and oral prednisone once daily on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: doxorubicin hydrochloride (Drug)
Interventional: 6 R-CHOP-21
Arm I (R-CHOP-21): Patients receive R-CHOP immunochemotherapy comprising rituximab IV, cyclophosphamide IV over 15 minutes, doxorubicin IV, and vincristine IV on day 1 and oral prednisone once daily on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: prednisone (Drug)
Interventional: 6 R-CHOP-21
Arm I (R-CHOP-21): Patients receive R-CHOP immunochemotherapy comprising rituximab IV, cyclophosphamide IV over 15 minutes, doxorubicin IV, and vincristine IV on day 1 and oral prednisone once daily on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: vincristine sulfate (Drug)
Interventional: 6 R-CHOP-21 + radiotherapy
Arm II (R-CHOP-21 and radiotherapy): Patients receive R-CHOP as in arm I. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Beginning 2-6 weeks after the last course of R-CHOP, patients who achieve a complete remission (CR) undergo radiotherapy 5 days a week for approximately 5½ weeks.
干预措施: rituximab (Biological)
Interventional: 6 R-CHOP-21 + radiotherapy
Arm II (R-CHOP-21 and radiotherapy): Patients receive R-CHOP as in arm I. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Beginning 2-6 weeks after the last course of R-CHOP, patients who achieve a complete remission (CR) undergo radiotherapy 5 days a week for approximately 5½ weeks.
干预措施: cyclophosphamide (Drug)
Interventional: 6 R-CHOP-21 + radiotherapy
Arm II (R-CHOP-21 and radiotherapy): Patients receive R-CHOP as in arm I. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Beginning 2-6 weeks after the last course of R-CHOP, patients who achieve a complete remission (CR) undergo radiotherapy 5 days a week for approximately 5½ weeks.
干预措施: doxorubicin hydrochloride (Drug)
Interventional: 6 R-CHOP-21 + radiotherapy
Arm II (R-CHOP-21 and radiotherapy): Patients receive R-CHOP as in arm I. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Beginning 2-6 weeks after the last course of R-CHOP, patients who achieve a complete remission (CR) undergo radiotherapy 5 days a week for approximately 5½ weeks.
干预措施: prednisone (Drug)
Interventional: 6 R-CHOP-21 + radiotherapy
Arm II (R-CHOP-21 and radiotherapy): Patients receive R-CHOP as in arm I. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Beginning 2-6 weeks after the last course of R-CHOP, patients who achieve a complete remission (CR) undergo radiotherapy 5 days a week for approximately 5½ weeks.
干预措施: vincristine sulfate (Drug)
Interventional: 6 R-CHOP-21 + radiotherapy
Arm II (R-CHOP-21 and radiotherapy): Patients receive R-CHOP as in arm I. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Beginning 2-6 weeks after the last course of R-CHOP, patients who achieve a complete remission (CR) undergo radiotherapy 5 days a week for approximately 5½ weeks.
干预措施: radiation therapy (Radiation)
Interventional: 6 R-CHOP-14
Arm III (R-CHOP-14): Patients receive R-CHOP as in arm I. Patients also receive filgrastim (G-CSF) subcutaneously once daily on days 4-13 or until blood counts recover. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: filgrastim (Biological)
Interventional: 6 R-CHOP-14
Arm III (R-CHOP-14): Patients receive R-CHOP as in arm I. Patients also receive filgrastim (G-CSF) subcutaneously once daily on days 4-13 or until blood counts recover. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: rituximab (Biological)
Interventional: 6 R-CHOP-14
Arm III (R-CHOP-14): Patients receive R-CHOP as in arm I. Patients also receive filgrastim (G-CSF) subcutaneously once daily on days 4-13 or until blood counts recover. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: cyclophosphamide (Drug)
Interventional: 6 R-CHOP-14
Arm III (R-CHOP-14): Patients receive R-CHOP as in arm I. Patients also receive filgrastim (G-CSF) subcutaneously once daily on days 4-13 or until blood counts recover. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: doxorubicin hydrochloride (Drug)
Interventional: 6 R-CHOP-14
Arm III (R-CHOP-14): Patients receive R-CHOP as in arm I. Patients also receive filgrastim (G-CSF) subcutaneously once daily on days 4-13 or until blood counts recover. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: prednisone (Drug)
Interventional: 6 R-CHOP-14
Arm III (R-CHOP-14): Patients receive R-CHOP as in arm I. Patients also receive filgrastim (G-CSF) subcutaneously once daily on days 4-13 or until blood counts recover. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: vincristine sulfate (Drug)
Interventional: 6 R-CHOP-14 and radiotherapy
Arm IV (R-CHOP-14 and radiotherapy): Patients receive R-CHOP as in arm I. Patients also receive G-CSF an in arm III. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Beginning 2-6 weeks after the last course of R-CHOP, patients who achieve CR undergo radiotherapy as in arm II.
干预措施: filgrastim (Biological)
Interventional: 6 R-CHOP-14 and radiotherapy
Arm IV (R-CHOP-14 and radiotherapy): Patients receive R-CHOP as in arm I. Patients also receive G-CSF an in arm III. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Beginning 2-6 weeks after the last course of R-CHOP, patients who achieve CR undergo radiotherapy as in arm II.
干预措施: rituximab (Biological)
Interventional: 6 R-CHOP-14 and radiotherapy
Arm IV (R-CHOP-14 and radiotherapy): Patients receive R-CHOP as in arm I. Patients also receive G-CSF an in arm III. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Beginning 2-6 weeks after the last course of R-CHOP, patients who achieve CR undergo radiotherapy as in arm II.
干预措施: cyclophosphamide (Drug)
Interventional: 6 R-CHOP-14 and radiotherapy
Arm IV (R-CHOP-14 and radiotherapy): Patients receive R-CHOP as in arm I. Patients also receive G-CSF an in arm III. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Beginning 2-6 weeks after the last course of R-CHOP, patients who achieve CR undergo radiotherapy as in arm II.
干预措施: doxorubicin hydrochloride (Drug)
Interventional: 6 R-CHOP-14 and radiotherapy
Arm IV (R-CHOP-14 and radiotherapy): Patients receive R-CHOP as in arm I. Patients also receive G-CSF an in arm III. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Beginning 2-6 weeks after the last course of R-CHOP, patients who achieve CR undergo radiotherapy as in arm II.
干预措施: prednisone (Drug)
Interventional: 6 R-CHOP-14 and radiotherapy
Arm IV (R-CHOP-14 and radiotherapy): Patients receive R-CHOP as in arm I. Patients also receive G-CSF an in arm III. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Beginning 2-6 weeks after the last course of R-CHOP, patients who achieve CR undergo radiotherapy as in arm II.
干预措施: vincristine sulfate (Drug)
Interventional: 6 R-CHOP-14 and radiotherapy
Arm IV (R-CHOP-14 and radiotherapy): Patients receive R-CHOP as in arm I. Patients also receive G-CSF an in arm III. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Beginning 2-6 weeks after the last course of R-CHOP, patients who achieve CR undergo radiotherapy as in arm II.
干预措施: radiation therapy (Radiation)
结局指标
主要结局
3 Years Event-free Survival
时间窗: Each patient will be observed for 3 years starting from completion of treatment.
Event-free survival was the primary endpoint, which was defined as the time from randomization until one of the following events had occurred: progression during therapy, partial response, no change, unknown status at the end of study therapy, relapse after complete response or unconfirmed complete response, death from any cause; or additional treatment, whichever came first.
次要结局
- 3 Years Progression-free Survival(Each patient will be observed for 3 years starting from completion of treatment.)
- 3 Years Overall Survival(Each patient will be observed for 3 years starting from completion of treatment.)
- Rate of Complete Remissions and Progressive Disease(Each patient will be observed for 3 years starting from completion of treatment.)
- Number of Patients With a Relapse After a CR/CRu(Each patient will be observed for 3 years starting from completion of treatment.)
- Safety (Adverse Events, Serious Adverse Events, Rate of Secondary Neoplasia, Selected Laboratory Parameters, Including Leucocytes, Thrombocytes, and Haemoglobin)(Each patient will be observed for 3 years starting from completion of treatment.)
- Adherence to Protocol - Absolute Dose Vincristine and Prednisone in mg (Median)(Each patient will be observed for 3 years starting from completion of treatment.)
- Health-economic Aspects - Number of Patients Who Received Antibiotic Intervention and/or Red Blood Cell and Platelet Transfusion(Each patient will be observed for 3 years starting from completion of treatment.)
- Adherence to Protocol - Total Duration of Chemotherapy in Days (Median)(Each patient will be observed for 3 years starting from completion of treatment.)
- Adherence to Protocol - Absolute Dose Cyclophosphamide, Doxorubicin and Rituximab in mg/m² (Median)(Each patient will be observed for 3 years starting from completion of treatment.)