A Multi-Center, Randomized, Phase 3 Study of Rituximab Versus Iodine I 131 Tositumomab Therapeutic Regimen For Patients With Relapsed Follicular Non-Hodgkins Lymphoma
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 14
- 试验地点
- 3
- 主要终点
- Event-free Survival (EFS)
研究概览
简要总结
Comparison of rituximab versus Iodine I 131 Tositumomab Therapeutic Regimen (Tositumomab and Iodine I 131 Tositumomab or the Bexxar Therapeutic Regimen, formerly called Iodine-131 Anti-B1 Antibody) in subjects with follicular non Hodgkins B cell lymphoma. 506 subjects will be enrolled at 30 to 40 sites in the US, Canada, and Europe. Subjects will be randomly assigned to one of two treatment arms. In Arm A, subjects will receive 375 milligrams/meter2 (mg/m2 )of rituximab, given as an intravenous (IV) infusion once weekly for 4 weeks. In Arm B, subjects will undergo a two-phase treatment. In the first phase, termed the "dosimetric dose," subjects will receive an infusion of unlabeled Tositumomab (450 mg) immediately followed by an infusion of 5 millicuries (mCi) (0.18 gigabecquerel [GBq]) of Iodine 131 Tositumomab (35 mg). Whole body gamma camera scans will be obtained three times (Day 0; Day 2, 3, or 4; and Day 6 or 7) following the dosimetric dose. The information derived from the scans will enable a patient specific dose to be calculated to deliver the desired total body dose of radiation (65 or 75 centigray [cGy]). In the second phase, termed the "therapeutic dose," subjects in Arm B will receive an infusion of unlabeled Tositumomab (450 mg) immediately followed by an infusion of the subject specific activity of Iodine 131-conjugated Tositumomab (35 mg). Thyroid blockade will be implemented 24 hours prior to the dosimetric dose and continued for 14 days following the therapeutic dose. Subjects on study will be followed for response and safety at Week 7, Week 13, and every three months for the first and second year, every six months for the third year, and then annually for the forth and fifth years; and then for vital status, additional therapy, and long term safety events through year ten. Follow Up after subsequent NHL therapy will be carried out to assess tolerance of next anti-lymphoma therapy, development of myelodysplasia (MDS)/acute myelogenous leukemia (AML), HAMA or hypothyroidism, unexpected safety issues, and death.
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
- •Histologically confirmed diagnosis of follicular lymphoma
- •Recurrent lymphoma after one or two qualifying therapy regimen(s)
- •Patients must not have progressed within 4 weeks of their last chemotherapy dose
- •Rituximab may have been used once as a single agent, in one continuous course of 4-8 weekly infusions (10-week period), or in combination with chemotherapy in a single prior treatment
- •Patients whose prior therapy includes rituximab must have had a 6 month or greater response duration following the rituximab-containing regimen.
- •Performance status of at least 70% on the Karnofsky Scale and an anticipated survival of at least three months
- •Adequate absolute neutrophil count and platelet count within 21 days of study entry without support of blood products/growth factors
- •Adequate renal function and adequate hepatic within 21 days of study entry
- •Measurable disease, with at least one lesion measuring >/=2.0 cm x 2.0 cm by CT scan
- •Human Anti Mouse Antigen negative
- •Written informed consent prior to study entry
排除标准
- •Histologic transformation to diffuse, large cell lymphoma.
- •History of more than one course of Rituximab
- •Disease limited to single lymph node or single group of nodes
- •Involvement of 25% of the intratrabecular marrow by bone marrow biopsy specimen.
- •Active infection requiring IV antibiotics at the time of study entry
- •New York Heart Association Class III/IV heart disease
- •Prior chemotherapy, biologic, radiation or steroid therapy for NHL within 8 weeks
- •Any prior radioimmunotherapy
- •Prior history of malignancy other than lymphoma (except for treated basal cell, squamous cell skin cancer, in situ cervical cancer, or other cancer that is disease-free for 5 years)
- •Known HIV infection
- •Hepatitis B positive
- •Known central nervous system involvement
研究组 & 干预措施
Tositumomab and Iodine I 131 Tositumomab
Dosimetric dose: 450 mg Tositumomab infused over 1 hour followed by 5 mCi I 131 Tositumomab infused over 20 minutes
Therapeutic dose: 450 mg Tositumomab infused over 1 hour followed by Individualized mCi activity of I 131 Tositumomab (35 mg) infused over 20 minutes.
干预措施: Tositumomab and Iodine I 131 Tositumomab (Biological)
Rituximab
Rituximab 375 mg/m2 given as an IV infusion once weekly for four weeks.
干预措施: Rituximab (Biological)
结局指标
主要结局
Event-free Survival (EFS)
时间窗: From the date of randomization to the first occurrence of progressive disease, death, or additional Non-Hodgkins Lymphoma (median follow-up for the Rituximab and TST/I-131 TST groups was 62 and 91.5 months, respectively)
Event-free survival is defined as the time from the date of randomization to the first occurrence of (whichever came first) progressive disease, death, or additional Non-Hodgkins Lymphoma (NHL) therapy due to disease-related symptoms, threatened end-organ function, cytopenias secondary to NHL, massive bulk disease, or steady progression over at least 6 months. Progressive disease is defined as at least a 50% increase in the sum of the perpendicular diameters of all measurable lesions and the appearance of new lesions at least 1.4 centimeters (cm) x 1.4 cm (i.e., 2.0 cm\^2) by radiographic evaluation or greater than 1.0 cm by palpation upon physical examination.
Progression-free Survival
时间窗: From first dose of treatment until disease progression or death, whichever came first (median follow-up for the Rituximab and TST/I-131 TST groups was 62 and 91.5 months, respectively)
Progression-free survival is defined as the time from the initial date of dosing to the first documented disease progression or death. Disease assessment was based on the International Workshop to Standardize Response Criteria (IWSRC) for Non-Hodgkin's Lymphoma (NHL). Progression is defined as at least a 50% increase in the sum of the perpendicular diameters of all measurable lesions and the appearance of new lesions at least 1.4 centimeters (cm) x 1.4 cm (i.e., 2.0 cm\^2) by radiographic evaluation or greater than 1.0 cm by palpation upon physical examination.
次要结局
- Hematologic Nadir for Platelet Count and White Blood Cell (WBC) Count(Time from study randomization to 120 days after study drug administration)
- Time to Nadir Values for the Indicated Hematological Parameters(Time from study randomization to 120 days after study drug administration)
- Number of Participants Achieving Response(Participants were followed for response at Week 7, Week 13, every 3 months for the first and second year, every 6 months for the third year, and then annually)
- Duration of Response(Participants were followed for response at Week 7, Week 13, every 3 months for the first and second year, every 6 months for the third year, and then annually)
- Time to Death(From first dose of treatment until disease progression or death, whichever came first (median follow-up for the Rituximab and TST/I-131 TST groups was 62 and 91.5 months, respectively))
- Number of Participants Who Had Died by the Month Indicated(From first dose of treatment until disease progression or death, whichever came first (median follow-up for the Rituximab and TST/I-131 TST groups was 62 and 91.5 months, respectively))
- Time to Next Treatment(Time from study randomization to 120 days after study drug administration)
- Hematologic Nadir for Absolute Neutrophil Count(Time from study randomization to 120 days after study drug administration)
- Hematologic Nadir for Hemoglobin(Time from study randomization to 120 days after study drug administration)
- Time to Recovery to Baseline Grade for the Indicated Hematological Parameters(Time from study randomization to 120 days after study drug administration)
- Duration of Grade 3/4 Toxicity for the Indicated Hematological Parameters(Time from study randomization to 120 days after study drug administration)
- Number of Participants That Developed Hypothyroidism(From the date of randomization to the first occurrence of progressive disease, death, or additional Non-Hodgkins Lymphoma (median follow-up for the Rituximab and TST/I-131 TST groups was 62 and 91.5 months, respectively))
- Number of Participants With an Infusion Reaction(First 24 hours of study drug administration.)
- Number of Hospitalizations(Time of treatment until 90 days post-treatment)
- Number of Participants With Myelodysplasia/Leukemia(From the date of randomization to the first occurrence of progressive disease, death, or additional Non-Hodgkins Lymphoma (median follow-up for the Rituximab and TST/I-131 TST groups was 62 and 91.5 months, respectively))
- Number of Participants With Any Serious Adverse Event (SAE) and Non-serious Adverse Event (AE)(From randomization through Week 26)