Radiotherapy Combined With Intratumoral Injections of Dendritic Cells and Rituximab - a Phase II Cancer Vaccine Trial for Patients With Untreated and Relapsed Indolent Non-Hodgkin's Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 14
- 试验地点
- 2
- 主要终点
- Response rate
研究概览
简要总结
Patients with non-curable disseminated follicular lymphoma receive local radiotherapy targeting single lymph nodes and injection of low-dose rituximab (anti-CD20) and autologous dendritic cells. The therapy is repeated 3 times, targeting different lesion. Aims are to induce tumor immunity and clinical responses.
详细描述
The clinical protocol is based on the rationale that the immune system has been developed to combat infectious disease. To mimic the environment in infected tissue, selected tumor-affected lymph nodes are treated locally with a single dose of 8 Gy radiotherapy and injected with therapeutic antibody (anti-CD20/Rituximab). Later, dendritic cells (DC) are injected into the damaged tumor tissue together with a stimulatory cytokine (GM-CSF) to initiate an immune response. Patients with untreated or relapsed stage III/IV follicular lymphoma not in need of standard therapy receive intra-tumoral injections of low-dose anti-CD20 antibodies (5 mg) on days 1 and 3 and local radiotherapy on day 2. On days 4 and 5, dendritic cells generated from monocytes isolated from the patients blood are injected into the site together with the stimulatory cytokine GM-CSF administered subcutaneously. Additional lymph nodes are treated similarly after 2 and 4 weeks. The treatment is thus performed three times, targeting different lymphoma nodes. The primary aims are to induce tumor-specific immune responses and clinical responses.
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 —(Adult, Older Adult)
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 years and older
- •Histologically confirmed (by WHO classification) untreated and relapsed indolent non-Hodgkin's B-cell lymphoma of low-grade follicular, marginal zone, lymphoplasmocytic or small lymphocytic subtypes.
- •Stage III/IV
- •Adequate bone marrow function (leukocyte count>2,0, neutrophil count>1.0, platelets>50)
- •Two or more separate lymph nodes > 1,5 cm available for biopsy or treatment.
- •Measurable disease present other than biopsy site and injection site(s).
- •Required wash-out period after previous treatment: Chemotherapy - 8 weeks, Radiotherapy - 4 weeks, Rituximab - 12 weeks
- •WHO status 0-1
- •Life expectancy of more than 6 months
- •Written informed consent
- •Able to comply with the treatment protocol -
排除标准
- •Patients with progressive lymphoma in need of systemic therapy or standard dose irradiation.
- •Chronic bacterial, viral or fungal infection
- •Pre-existing autoimmune or antibody mediated disease including: systemic lupus, erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome, autoimmune thrombocytopenia, but excluding controlled thyroid disease, or the presence of autoantibodies without clinical autoimmune disease.
- •Known history of HIV
- •Central nervous system involvement of lymphoma
- •Current anticoagulant therapy which can not safely be paused during treatment injections (ASA < 325 mg/day allowed)
- •Pregnancy -
结局指标
主要结局
Response rate
时间窗: 5 years
Clinical response measured by CT and PET/CT and immune response
次要结局
- Immune response(1 year)
