Use of Rituximab in Opsoclonus-Myoclonus in Children With Neuroblastoma
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 4
- 主要终点
- Feasibility of Using 4 Weekly Rituximab Infusions
研究概览
简要总结
The purpose of this study is to evaluate the feasibility of giving four weekly doses of Rituximab (anti-CD20 antibody) in the treatment of children with refractory neuroblastoma associated opsoclonus-myoclonus. Patients must have continued symptoms of opsoclonus, myoclonus and or ataxia despite surgical resection and a minimum of one month of steroid therapy. Evaluations include clinical symptoms of opsoclonus-myoclonus and ataxia as well as detailed evaluation of learning and development.
详细描述
Opsoclonus-myoclonus ataxia syndrome (OMS) is a rare immune mediated paraneoplastic syndrome that occurs in approximately 2 to 3% of children with neuroblastoma. Children with neuroblastoma associated opsoclonus-myoclonus tend to have a favorable prognosis from the standpoint of the cure of their cancer. Unfortunately,approximately two-thirds of this subgroup of patients are left with long term sequellae of the syndrome, including residual symptoms of opsoclonus, myoclonus, ataxia, learning difficulties and disturbance of sleep and mood.
Multiple lines of evidence indicate an immune mechanism to this rare disorder. This includes occurence of OMS in the post-infectious state, aggressive lymphocytic infiltration of the tumor in children with OMS, and documented responses to therapries that act through suppression of the immune system.
The current study utilizes four weekly doses of anti-CD 20 antibody (rituximab) to treat children with refractory OMS. Refractory disease is defined as continued symptoms of OMS despite surgical resection of the tumor and a minimum of one month of steroid therapy.
All patients have baseline OMS evaluation and detailed neurocognitive testing with all studies being repeated at the completion of the four weekly infusions. OMS testing is repeated at Month 3. OMS testing and detailed neurocognitive testing is conducted at 6 months intervals until 2 years from the initial infusion.
The goal of the study is to utilize this novel therapy to improve long term neurologic and neurodevelopmental outcome in children with refratory neuroblastoma associated opsoclonus-myoclonus.
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
- 2 Months 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Pathologic confirmation of diagnosis of neuroblastoma Surgical resection of primary tumor Symptoms of OMS despite a minimum of one month of steroid therapy Must meet all laboratory criteria to demonstrate adequate organ function -
排除标准
- •Patients currently receiving systemic chemotherapy for treatment of neuroblastoma Patients with documented active infection Patients who are HIV, Hep B or Hep C positive Organ toxicity from any prior therapy or surgical intervention must be resolved prior to study entry
研究组 & 干预措施
Rituximab
Single Arm
干预措施: anti-CD20 (Rituximab) (Drug)
结局指标
主要结局
Feasibility of Using 4 Weekly Rituximab Infusions
时间窗: 4 weeks
To evaluate the feasibility of using 4 weekly Rituximab infusions in the treatment of children with neuroblastoma associated opsoclonus-myoclonus syndrome (OMS). The first infusion involved a slow up titration from an initial rate of 0.5 mg/kg/hour to a maximum of 400 mg/hour. If well tolerated, the subsequent infusions were administered at a starting rate of 1 mg/kg/hour to a maximum of 100 mg/hour for the first hour. In the absence of adverse reaction doses were escalated by 1 mg/kg/hour (maximum 100 mg increase per hour) every 30 minutes to a maximum rate of 400 mg/hour. If hypersensitivity or infusion related events occurred, the infusion was temporarily interrupted and resumed at 50% of the previous rate if reaction resolves. The number of participants for whom the study dosing was feasible is reported.
Toxicity of Rituximab
时间窗: Individuals were followed for adverse events until day 270
The trial was to be terminated early for any grade 3 or 4 toxicity that did not resolve in 2 of the first 5 patients treated, or for any infusion related death. The number of participants who experienced these events \[grade 3 or 4 toxicity that did not resolve in 2 of the first 5 patients treated, or for any infusion related death\] is reported.
次要结局
- OMS Evaluation Scale of Motor-Performance(Baseline, following the four infusions, at months 3, 6, 12, 18 and 24 following the first infusion.)
- Peripheral B Cell Depletion(2 years)
- Human-anti-chimeric Antibody (HACA) Development(Baseline; 3, 6, 9 months post treatment)
研究者
Jean M. Tersak, M.D.
Professor
University of Pittsburgh