A Phase III Trial of CHOP Plus Rituximab vs CHOP Plus Iodine-131-Labeled Monoclonal Anti-B1 Antibody (Tositumomab) for Treatment of Newly Diagnosed Follicular Non-Hodgkin's Lymphomas
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 571
- 试验地点
- 259
- 主要终点
- Progression-free Survival at 2 Years
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies can locate tumor cells and either kill them or deliver radioactive tumor-killing substances to them without harming normal cells. It is not yet known which monoclonal antibody plus combination chemotherapy regimen is more effective in treating non-Hodgkin's lymphoma.
PURPOSE: This randomized phase III trial is comparing 2 different monoclonal antibodies given together with combination chemotherapy to see how well they work in treating patients with newly-diagnosed non-Hodgkin's lymphoma.
详细描述
OBJECTIVES:
- Compare the progression-free survival and overall survival of patients with newly diagnosed follicular non-Hodgkin's lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with or without either rituximab or iodine I 131 tositumomab (monoclonal antibody anti-B1). (CHOP chemotherapy alone arm closed to accrual as of 12/15/02)
- Compare the response rate of these patients treated with these regimens.
- Compare the toxic effects of these regimens in these patients.
- Compare the molecular remission rates of this patient population treated with these regimens.
- Determine the incidence and time to development of human anti-mouse antibody positivity.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to whether microglobulin is greater than upper limit of normal (yes vs no). Patients are randomized to 1 of 3 treatment arms. (Arm I closed to accrual as of 12/15/02)
- Arm I (CHOP only): Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on day 1. Patients also receive oral prednisone daily on days 1-5. Treatment continues every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. (Arm I closed to accrual as of 12/15/02)
- Arm II (CHOP + rituximab): Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on days 8, 29, 50, 71, 92, and 113. Patients also receive oral prednisone daily on days 8-12, 29-33, 50-54, 71-75, and 113-117 and rituximab IV over 4-6 hours on days 1, 6, 48, 90, 134, and 141.
- Arm III (CHOP + tositumomab): Patients receive chemotherapy as in arm I and tositumomab (monoclonal antibody anti-B1) IV over 1 hour followed by iodine I 131 tositumomab IV over 20 minutes on days 134 and 141.
Patients are followed on day 200, at 1 year, every 6 months for 2 years, and then annually thereafter.
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
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed previously untreated bulky stage II or stage III or IV follicular non-Hodgkin's lymphoma
- •Grade I-III disease
- •Cluster of differentiation antigen 20 (CD20) antigen positive
- •Fewer than 5,000/mm^3 circulating lymphoid cells on a white blood cell (WBC) differential count
- •Bidimensionally measurable disease
- •Bone marrow aspiration and biopsy within the past 42 days
- •No clinical evidence of central nervous system (CNS) involvement by lymphoma
- •PATIENT CHARACTERISTICS:
- •18 and over
- •Performance status:
- •Zubrod 0-2
- •Life expectancy:
- •Not specified
- •Hematopoietic:
- •See Disease Characteristics
- •Granulocyte count greater than 1,500/mm^3
- •Platelet count greater than 100,000/mm^3
- •Not specified
- •Not specified
- •Cardiovascular:
- •No impaired cardiac status, including:
- •Severe coronary artery disease
- •Cardiomyopathy
- •Congestive heart failure
- •Serious arrhythmia
- •Ejection fraction at least lower limit of normal by Multi Gated Acquisition Scan (MUGA) or 2-D echocardiogram for questionable cardiac history
- •No hypersensitivity to iodine
- •Not pregnant or nursing
- •Fertile patients must use effective contraception during and for 6 months after study participation
- •HIV negative
- •No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy:
- •No prior monoclonal antibodies for cancer
- •Chemotherapy:
- •No prior chemotherapy for lymphoma
- •Prior prednisone for non-lymphoma related illnesses allowed
- •Endocrine therapy:
- •Not specified
- •Radiotherapy:
- •No prior radiotherapy for lymphoma
- •See Disease Characteristics
排除标准
- 未提供
研究组 & 干预措施
Arm I (CHOP only)
Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on day
1. Patients also receive oral prednisone daily on days 1-5. Treatment continues every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. (Arm I closed to accrual as of 12/15/02)
干预措施: cyclophosphamide (Drug)
Arm I (CHOP only)
Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on day
1. Patients also receive oral prednisone daily on days 1-5. Treatment continues every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. (Arm I closed to accrual as of 12/15/02)
干预措施: doxorubicin (Drug)
Arm I (CHOP only)
Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on day
1. Patients also receive oral prednisone daily on days 1-5. Treatment continues every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. (Arm I closed to accrual as of 12/15/02)
干预措施: prednisone (Drug)
Arm I (CHOP only)
Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on day
1. Patients also receive oral prednisone daily on days 1-5. Treatment continues every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. (Arm I closed to accrual as of 12/15/02)
干预措施: vincristine (Drug)
Arm II (CHOP + rituximab)
Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on days 8, 29, 50, 71, 92, and 113. Patients also receive oral prednisone daily on days 8-12, 29-33, 50-54, 71-75, and 113-117 and rituximab IV over 4-6 hours on days 1, 6, 48, 90, 134, and 141.
干预措施: rituximab (Biological)
Arm II (CHOP + rituximab)
Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on days 8, 29, 50, 71, 92, and 113. Patients also receive oral prednisone daily on days 8-12, 29-33, 50-54, 71-75, and 113-117 and rituximab IV over 4-6 hours on days 1, 6, 48, 90, 134, and 141.
干预措施: cyclophosphamide (Drug)
Arm II (CHOP + rituximab)
Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on days 8, 29, 50, 71, 92, and 113. Patients also receive oral prednisone daily on days 8-12, 29-33, 50-54, 71-75, and 113-117 and rituximab IV over 4-6 hours on days 1, 6, 48, 90, 134, and 141.
干预措施: doxorubicin (Drug)
Arm II (CHOP + rituximab)
Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on days 8, 29, 50, 71, 92, and 113. Patients also receive oral prednisone daily on days 8-12, 29-33, 50-54, 71-75, and 113-117 and rituximab IV over 4-6 hours on days 1, 6, 48, 90, 134, and 141.
干预措施: prednisone (Drug)
Arm II (CHOP + rituximab)
Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on days 8, 29, 50, 71, 92, and 113. Patients also receive oral prednisone daily on days 8-12, 29-33, 50-54, 71-75, and 113-117 and rituximab IV over 4-6 hours on days 1, 6, 48, 90, 134, and 141.
干预措施: vincristine (Drug)
Arm III (CHOP + tositumomab)
Patients receive chemotherapy as in arm I and tositumomab (monoclonal antibody anti-B1) IV over 1 hour followed by iodine I 131 tositumomab IV over 20 minutes on days 134 and 141.
干预措施: cyclophosphamide (Drug)
Arm III (CHOP + tositumomab)
Patients receive chemotherapy as in arm I and tositumomab (monoclonal antibody anti-B1) IV over 1 hour followed by iodine I 131 tositumomab IV over 20 minutes on days 134 and 141.
干预措施: doxorubicin (Drug)
Arm III (CHOP + tositumomab)
Patients receive chemotherapy as in arm I and tositumomab (monoclonal antibody anti-B1) IV over 1 hour followed by iodine I 131 tositumomab IV over 20 minutes on days 134 and 141.
干预措施: prednisone (Drug)
Arm III (CHOP + tositumomab)
Patients receive chemotherapy as in arm I and tositumomab (monoclonal antibody anti-B1) IV over 1 hour followed by iodine I 131 tositumomab IV over 20 minutes on days 134 and 141.
干预措施: vincristine (Drug)
Arm III (CHOP + tositumomab)
Patients receive chemotherapy as in arm I and tositumomab (monoclonal antibody anti-B1) IV over 1 hour followed by iodine I 131 tositumomab IV over 20 minutes on days 134 and 141.
干预措施: tositumomab (Radiation)
结局指标
主要结局
Progression-free Survival at 2 Years
时间窗: 0-2 years
Measured from time of registration to date of of first observation of progression/relapse, or death due to any cause, or last contact date
Overall Survival at 5 Years
时间窗: 0-5 years
Measured from date of registration to date of death due to any cause
Progression-free Survival at 5 Years
时间窗: 0-5 years
Measured from time of registration to date of of first observation of progression/relapse, or death due to any cause, or last contact date
Overall Survival at 2 Years
时间窗: 0-2 years
Measured from date of registration to date of death due to any cause
次要结局
- Objective Response (Confirmed and Unconfirmed Complete and Partial Responses)(Assessed 200 days and 365 days after initiation of therapy and then every 6 months until death)
- Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug(Patients were assessed for adverse events at end of cycle 1-6 of CHOP or R-CHOP, the end of cycle 1-6 of CHOP and once 2 weeks after the completion of I-131 treatment. For either arm, once 3 months after removal from protocol treatment)