Multicenter European Pilot Study of 90Yttrium-Ibritumomab Tiuxetan as First Line Therapy for Stage III - IV Follicular Lymphoma (and Selected Patients With Extended Stage II) Followed by Consolidation Rituximab for Patients in Complete Remission But With Persistent Molecular Disease
试验速览
- 阶段
- 2 期
- 入组人数
- 60
- 主要终点
- Clinical and molecular remission rate after primary therapy with 90Y-Ibritumomab Tiuxetan
研究概览
简要总结
This is a European multicenter study of 90Yttrium-Ibritumomab Tiuxetan (90Y-Ibritumomab Tiuxetan) (Zevalin®) as a front line therapy for patients with follicular lymphoma grade I-IIIa and stage III-IV (as well as for selected patients with extended abdominal stage II). For patients with complete clinical remission but persistent molecular disease subsequent to 90Y-Ibritumomab Tiuxetan treatment a consolidation immunotherapy with Rituximab is added, to eradicate minimal residual disease.
详细描述
Only patients requiring treatment (B-symptoms, lymphoma progression > 50% within an observation period of 6 months or less, organ compression by lymphoma or bulky disease as defined by lesions above 5 cm on one axis) may enter the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient > 50 years old
- •Follicular lymphoma grade I, II, or IIIa according to REAL/WHO classification
- •Ann Arbor stage III, or IV, or stage II with disseminated abdominal disease requiring extensive abdominal irradiation
- •No prior chemotherapy, immunotherapy, or irradiation. Furthermore, when receiving therapy as part of this "Zevalin® first line in follicular lymphoma" trial and up to six months after therapy has ended, patients may not participate in another clinical trial. If patients receive consolidation therapy with Rituximab, the six months period is counted from the end of the consolidation therapy.
- •Lymphoma cells positive for CD20
- •Measurable disease (two perpendicular diameters by either physical or radiological examination)
- •WHO/ECOG performance status 0 - 2
- •Written informed consent
排除标准
- •Bone marrow involvement only
- •Bone marrow infiltration > 25%
- •Leukocytopenia < 2.500 /µl
- •Thrombocytopenia < 100.000 /µl
- •Bulk lesions > 10 cm
- •CNS lymphoma manifestation
- •Circulating tumor cells > 500 /µl
- •Extensive pleural effusion/ascites (> 1000 ml as estimated by ultrasound/CT)
- •Severe concomitant diseases (e.g. congestive heart failure, myocardial infarction within 6 months of study, severe uncontrolled hypertension, renal insufficiency requiring hemodialysis, pulmonary disease, liver disease)
- •Abnormal liver function: transaminases or total bilirubin > 2 x upper limit of normal (ULN) (unless caused by the lymphoma)
- •Abnormal renal function: serum creatinine > 2 x upper limit of normal (unless caused by the lymphoma)
- •Previous malignancy other than non-melanoma skin cancer
- •Pregnant or breast feeding female patients (negative pregnancy test required for women of fertile age), no effective contraception
- •HIV positivity
- •Known hypersensitivity to foreign proteins, murine antibodies, presence of human anti-murine antibodies (HAMA) reactivity
- •Severe psychiatric illness
研究组 & 干预措施
Study Therapy
Induction therapy with a single course of 90Yttrium-Ibritumomab Tiuxetan (according to the standard procedure that includes Rituximab 250 mg/m2 plus 111Indium-Ibritumomab Tiuxetan for dosimetry on day one followed by Rituximab 250 mg/m2 and 90Y-Ibritumomab Tiuxetan 15 MBq/kg on day 8 or 9 up to a maximal dose of 12.000 MBq [if platelets are below 150000/µl only 11 MBq/kg are administered). Observation for patients achieving complete clinical and molecular response or partial clinical response. Consolidation/maintenance therapy with 4 weekly courses of Rituximab 375 mg/m2 followed by 4 bimonthly courses of Rituximab 375 mg/m2 for patients in clinical CR but with persistent Bcl-2 (t14;18)-positivity 6 months after 90Y-Ibritumomab Tiuxetan.
干预措施: 90Yttrium-Ibritumomab Tiuxetan (Zevalin®)+Rituximab (Drug)
Study Therapy
Induction therapy with a single course of 90Yttrium-Ibritumomab Tiuxetan (according to the standard procedure that includes Rituximab 250 mg/m2 plus 111Indium-Ibritumomab Tiuxetan for dosimetry on day one followed by Rituximab 250 mg/m2 and 90Y-Ibritumomab Tiuxetan 15 MBq/kg on day 8 or 9 up to a maximal dose of 12.000 MBq [if platelets are below 150000/µl only 11 MBq/kg are administered). Observation for patients achieving complete clinical and molecular response or partial clinical response. Consolidation/maintenance therapy with 4 weekly courses of Rituximab 375 mg/m2 followed by 4 bimonthly courses of Rituximab 375 mg/m2 for patients in clinical CR but with persistent Bcl-2 (t14;18)-positivity 6 months after 90Y-Ibritumomab Tiuxetan.
干预措施: Rituximab (Drug)
结局指标
主要结局
Clinical and molecular remission rate after primary therapy with 90Y-Ibritumomab Tiuxetan
时间窗: 6 months from entry onto trial
次要结局
- Time to progression after treatment with 90Y-Ibritumomab Tiuxetan(5 years from entry onto trial)
- Ability of consolidation therapy with Rituximab to induce molecular remission for CR patients not achieving molecular remission within 6 months after 90Y-Ibritumomab Tiuxetan(5 years from entry onto trial)
- Safety and tolerability of 90Y-Ibritumomab Tiuxetan with particular respect to further therapy strategies in relapsed patients(5 years from entry onto trial)
研究者
Christian Scholz M.D.
PD Dr. med. Christian Scholz
Charite University, Berlin, Germany