Cyclophosphamide in Myalgic Encephalopathy/ Chronic Fatigue Syndrome (ME/CFS). Part A: an Open Label Phase-II Study With Six Intravenous Cyclophosphamide Infusions Four Weeks Apart, and Follow-up for 12 Months
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Fatigue score, selfreported
研究概览
简要总结
Significant clinical improvements of ME/CFS symptoms were observed in two patients with long-standing ME/CFS who received adjuvant chemotherapy including cyclophosphamide for breast cancer, also in one ME/CFS patient who received chemotherapy including iphosphamide for Hodgkin lymphoma.
Three pilot ME/CFS patients were thereafter treated with six intravenous infusions four weeks apart, in two of these with a significant clinical response.
The hypothesis is that a subset of ME/CFS patients have an activated immune system, and that ME/CFS symptoms may be alleviated by treatment with cyclophosphamide as intravenous pulse infusions four weeks apart, six infusions in total.
The purpose of the present study is to treat ME/CFS patients with cyclophosphamide as intravenous pulse infusions four weeks apart, six infusions in total. The effects on ME/CFS symptoms and tolerability/side effects during 12 months follow-up will be registered, and additional tests will be performed to objectively register changes in physical ability during follow-up. Studies to investigate possible large vessel endothelial dysfunction and skin microvascular dysfunction will be performed before start of intervention and during follow-up.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with ME/CFS according to "Canadian" criteria (2003)
- •Duration of ME/CFS at least 2 years
- •Mild/Moderate, Moderate, Moderate/Severe and Severe ME/CFS may be included
- •Age 18-65 years
- •Signed informed consent
排除标准
- •Patients with fatigue who do not comply by the diagnostic "Canadian" criteria (2003) for ME/CFS
- •Duration of ME/CFS less than 2 years
- •Mild ME/CFS
- •Very severe ME/CFS (bedridden requiring help for all tasks)
- •Patients where the workup uncovers other pathology as possible cause of symptoms
- •Pregnancy or breast feeding
- •Previous malignant disease (except basal cell carcinoma of skin and cervical carcinoma in situ/dysplasia)
- •Previous long-term systemic treatment with immunosuppressive agents (e.g. azathioprine, ciclosporin, mycophenolate mofetil). Except steroid treatment for e.g. obstructive lung disease or autoimmune diseases such as e.g. ulcerative colitis
- •Serious endogenous depression
- •Lack of ability to complete the study including follow-up
- •Reduced renal function (creatinine > 1.5 x UNL)
- •Reduced liver function (bilirubin or transaminases > 1.5 x UNL)
- •Known hypersensitivity to cyclophosphamide or metabolites
- •Reduced bone marrow function
- •Ongoing cystitis or urinary tract obstruction
- •Known HIV positivity, previous hepatitis B or hepatitis C, or reason to suspect other ongoing and clinically relevant infection
研究组 & 干预措施
Cyclophosphamide
Cyclophosphamide, intravenous infusions four weeks apart. Six infusions in total. First infusion: 600 mg/m2. Infusions 2 to 6: 700 mg/m2
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Fatigue score, selfreported
时间窗: Within 12 months follow-up
Selfreported Fatigue score is registered every second week, always compared to baseline, as the mean of the four symptoms: "Post-exertional malaise", "Fatigue", "Need for rest", Daily functioning" (scale 0-6, in which 3 is unchanged from baseline). Mean Fatigue scores for the time intervals 0-3, 3-6, 6-9 and 9-12 months are recorded for each patient. Changes in selfreported Fatigue scores from baseline to the mean values in each of the time intervals 0-3, 3-6, 6-9 and 9-12 months follow up, will constitute the primary endpoint. Responses for the primary endpoint will be recorded separately for the group of (at least) 25 ME/CFS patients not given rituximab previously, for the group with previous rituximab intervention for ME/CFS with no clinical response and for the group with previous rituximab intervention with clinical response but later relapse, and also for all 40 included patients together.
Overall response
时间窗: Within 12 months follow-up
Overall response is recorded as the effect on ME/CFS symptoms during 12 months follow-up. The overall response is not predefined to a specific time interval during follow-up, but is defined as mean Fatigue score at least 4.5 for at least 6 consecutive weeks for moderate response, and mean Fatigue score at least 5.0 for at least 6 consecutive weeks for major response. Single response periods and the sum of response periods during 12 months follow-up will be recorded. Overall response will be recorded separately for the group of (at least) 25 ME/CFS patients not given rituximab previously, for the group with previous rituximab intervention for ME/CFS with no clinical response and for the group with previous rituximab intervention with clinical response but later relapse, and also for all 40 included patients together.
次要结局
- Short Form-36 (SF-36)(Recorded at baseline, and at 3, 6, 9 and 12 months follow-up.)
- Physical activity (Sensewear armband)(Recorded at baseline, at 7-9 months, and at 11-12 months)
- Fatigue Severity Scale(Baseline, 3, 6, 9 and 12 months)
- Longest continuous response duration(Within 12 months follow-up)
- Sustained clinical response at 12 months(Assessment at end of follow-up (12 months))
- Safety and tolerability(Continuously within the study period of 12 months)
- Cardiopulmonary exercise tests for two following days(At baseline, and repeated at 7-9 months, and 11-12 months)
- Self-recorded Function level(At baseline, and at 3, 6, 9 and 12 months follow-up)