Iodine-131-Labeled Monoclonal Anti-B1 Antibody (I-131 Tositumomab) in Combination With Cyclophosphamide, Doxorubicin, Vincristine, Prednisone and Rituximab Therapy for Patients ≥ Age 60 With Advanced Stage Diffuse Large B-Cell NHL: A Phase II Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 86
- 试验地点
- 77
- 主要终点
- Progression-free Survival (PFS) at 2 Years
研究概览
简要总结
RATIONALE: Radiolabeled monoclonal antibodies, such as iodine I 131 tositumomab, can find cancer cells and carry cancer-killing substances to them without harming normal cells. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, 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. Giving a radiolabeled monoclonal antibody together with rituximab and combination chemotherapy may kill more cancer cells.
PURPOSE: This phase II trial is studying how well giving iodine I 131 tositumomab together with rituximab and combination chemotherapy works in treating older patients with stage II, stage III, or stage IV B-cell non-Hodgkin's lymphoma.
详细描述
OBJECTIVES:
- Determine the 2-year progression-free survival of older patients with previously untreated bulky stage II or stage III or IV diffuse large B-cell non-Hodgkin's lymphoma treated with iodine I 131 tositumomab in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone.
- Determine the response rate (partial response, complete unconfirmed response, and complete response) in patients treated with this regimen.
- Determine the 2-year progression-free survival and response rate (partial response, complete unconfirmed response, and complete response) in B-cell lymphoma 2 (BCL-2) positive patients treated with this regimen.
OUTLINE: This is a multicenter study.
- Rituximab and chemotherapy: Patients receive R-CHOP comprising rituximab IV over 6 hours; cyclophosphamide IV over 15-45 minutes; doxorubicin IV over 5-20 minutes; and vincristine IV over 5-15 minutes on day 1 and oral prednisone on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo a restaging evaluation. Patients without progressive disease receive CHOP chemotherapy comprising cyclophosphamide, doxorubicin, vincristine, and prednisone as outlined above. Treatment with CHOP chemotherapy repeats every 21 days for 2 courses.
- Radiolabeled monoclonal antibody therapy: Approximately 4-8 weeks after completion of chemotherapy, patients receive tositumomab IV over 1 hour followed by a dosimetric dose of iodine I 131 tositumomab IV over 20 minutes. Patients then undergo gamma scans over a 1-week period in order to determine the correct treatment dose of iodine I 131 tositumomab. No more than 2 weeks after administration of the dosimetric dose, patients receive tositumomab IV over 1 hour followed by a treatment dose of iodine I 131 tositumomab IV over 20 minutes.
After completion of study treatment, patients are followed periodically for up to 5 years.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 120 Years（Adult, Older 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
R-CHOP x 8 with I-131 Tositumomab
Cyclophosphamide 750 mg/m2 IV Day 1 Doxorubicin 50 mg/m2 IV Day 1 Vincristine 1.4 mg/m2 IV Day 1 Prednisone 100 mg PO Days 1-5 Rituximab 375 mg/m2 IV Day 1 Q 21 Days x 6 cycles
Unlabeled Anti-B1 Antibody 450 mg IV Day 170 Dosimetric dose 35 mg IV Day 170
Unlabeled Anti-B1 Antibody 450 mg IV Day 177 Therapeutic dose 35 mg IV Day 177
干预措施: rituximab (Biological)
R-CHOP x 8 with I-131 Tositumomab
Cyclophosphamide 750 mg/m2 IV Day 1 Doxorubicin 50 mg/m2 IV Day 1 Vincristine 1.4 mg/m2 IV Day 1 Prednisone 100 mg PO Days 1-5 Rituximab 375 mg/m2 IV Day 1 Q 21 Days x 6 cycles
Unlabeled Anti-B1 Antibody 450 mg IV Day 170 Dosimetric dose 35 mg IV Day 170
Unlabeled Anti-B1 Antibody 450 mg IV Day 177 Therapeutic dose 35 mg IV Day 177
干预措施: cyclophosphamide (Drug)
R-CHOP x 8 with I-131 Tositumomab
Cyclophosphamide 750 mg/m2 IV Day 1 Doxorubicin 50 mg/m2 IV Day 1 Vincristine 1.4 mg/m2 IV Day 1 Prednisone 100 mg PO Days 1-5 Rituximab 375 mg/m2 IV Day 1 Q 21 Days x 6 cycles
Unlabeled Anti-B1 Antibody 450 mg IV Day 170 Dosimetric dose 35 mg IV Day 170
Unlabeled Anti-B1 Antibody 450 mg IV Day 177 Therapeutic dose 35 mg IV Day 177
干预措施: doxorubicin hydrochloride (Drug)
R-CHOP x 8 with I-131 Tositumomab
Cyclophosphamide 750 mg/m2 IV Day 1 Doxorubicin 50 mg/m2 IV Day 1 Vincristine 1.4 mg/m2 IV Day 1 Prednisone 100 mg PO Days 1-5 Rituximab 375 mg/m2 IV Day 1 Q 21 Days x 6 cycles
Unlabeled Anti-B1 Antibody 450 mg IV Day 170 Dosimetric dose 35 mg IV Day 170
Unlabeled Anti-B1 Antibody 450 mg IV Day 177 Therapeutic dose 35 mg IV Day 177
干预措施: prednisone (Drug)
R-CHOP x 8 with I-131 Tositumomab
Cyclophosphamide 750 mg/m2 IV Day 1 Doxorubicin 50 mg/m2 IV Day 1 Vincristine 1.4 mg/m2 IV Day 1 Prednisone 100 mg PO Days 1-5 Rituximab 375 mg/m2 IV Day 1 Q 21 Days x 6 cycles
Unlabeled Anti-B1 Antibody 450 mg IV Day 170 Dosimetric dose 35 mg IV Day 170
Unlabeled Anti-B1 Antibody 450 mg IV Day 177 Therapeutic dose 35 mg IV Day 177
干预措施: vincristine sulfate (Drug)
R-CHOP x 8 with I-131 Tositumomab
Cyclophosphamide 750 mg/m2 IV Day 1 Doxorubicin 50 mg/m2 IV Day 1 Vincristine 1.4 mg/m2 IV Day 1 Prednisone 100 mg PO Days 1-5 Rituximab 375 mg/m2 IV Day 1 Q 21 Days x 6 cycles
Unlabeled Anti-B1 Antibody 450 mg IV Day 170 Dosimetric dose 35 mg IV Day 170
Unlabeled Anti-B1 Antibody 450 mg IV Day 177 Therapeutic dose 35 mg IV Day 177
干预措施: tositumomab and iodine I 131 tositumomab (Radiation)
结局指标
主要结局
Progression-free Survival (PFS) at 2 Years
时间窗: 0-2 years
Clinical responses were evaluated according to International Workshop NHL criteria (Cheson et al, 1999). Progression disease was defined as if a (CR, CRU) was not achieved at a previous assessment, a 50% increase in the SPD of target measurable lesions over the smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline. Appearance of a new lesion/site. Unequivocal progression of non-measurable disease in the opinion of the treating physician (an explanation must be provided). Death due to disease without prior documentation of progression. PFS is measured from date of registration to date of first observation of progressive disease, or death due to any cause. Patients last known to be alive and progression-free are censored at date of last contact.
Response Rate (Complete, Complete Unconfirmed, and Partial)
时间窗: 6 months
Complete Response(CR) is a complete disappearance of all disease with the exception of nodes. No new lesions. previously enlarged organs must have regressed and not be palpable. Bone marrow(BM) must be negative if positive at baseline. Normalization of markers. CR Unconfirmed (CRU) does not qualify for CR above, due to a residual nodal mass or an indeterminate BM. Partial Response(PR) is a 50% decrease in the sum of products of greatest diameters (SPD) for up to 6 identified dominant lesions, including spleenic and hepatic nodules from baseline. No new lesions and no increase in the size of liver, spleen or other nodes.
次要结局
- Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug(6 months (assessed at the end of each cycle of chemotherapy for 8 cycles (1 cycle= 21 days), at restaging, and at the end of each radiolabeled antibody treatment))