Highdose Chemotherapy and Transplantation of 34+ Selected Stem Cell for Progressive Systemic Sclerosis - Modification According to Manifestation
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Efficay - Overall survival
研究概览
简要总结
Autologous stem cell therapy has been shown to be effective in patients with systemic sclerosis. Nevertheless treatment is associated with treatment related mortality and patients die during follow up despite successful transplantation.
Intention of this trial is to improve overall survival by modifying the existing protocol used for the ASTIS trial.
To reduce treatment toxicity we reduce the dose of Cyclophosphamide (CYC) for mobilisation to 2x1g.
Especially in patients with cardiac manifestations we also modify the conditioning regimen by adding thiotepa and reducing CYC; as CYC has known cardiotoxic side effects.
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
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of progressive systemic sclerosis <7 years
- •Progressive course despite cyclophosphamide pretreatment
- •Cyclophosphamide i.v.: at least 3 x with 500-1000 mg/m² every 3-4 weeks or
- •Cyclophosphamide p.o. with at least 100mg/day for at least 2 months or
- •Contraindication to treatment with cyclophosphamide
- •Progress defined as at least one of the following criteria:
- •Increase in the mRSS
- •Worsening of the lung function
- •Increase in fibrosis/alveolitis in thorax CT
- •Worsening kidney function through manifestation of systemic sclerosis
- •Limited or diffuse cutaneous progressive form of Ssc with organ manifestation in the lungs/heart or kidneys
排除标准
- •Age <18 years
- •Pregnancy or inadequate contraception
- •Severe heart failure with ejection fraction (EF) < 30% in echo
- •Pulmonary arterial hypertension with systolic pulmonary arterial pressure (PAPsys) >50mm Hg
- •Kidney insufficiency: creatinine clearance <30 ml/min
- •Reduced lung function
- •Inspiratory vital capacity (IVC) < 50% of normal
- •Carbon monoxide (CO)-Diffusion capacity SB < 40%
- •Previously damaged bone marrow
- •Leukopenia < 2,000/µl
- •Thrombopenia < 100,000/µl
- •Previous myelotoxic treatment:
- •Cyclophosphamide > 50g cumulative (relative)
- •Infection (Hepatitis B/C, HIV, Salmonella carrier, syphilis, relative: history of tuberculosis)
- •Severe concomitant psychiatric illness (depression, psychosis)
- •Substance dependence
- •Continued nicotine abuse
- •Continued alcohol abuse
- •Continued drug abuse
- •Consent not given
- •Poor compliance
研究组 & 干预措施
Conditioning with CYC/ antithymocyte globulin (ATG)
Each patient receives stem cell transplantation open label with cluster of differentiation (CD)34 selected stem cells mobilisation and conditioning depending on manifestation If cardiac manifestation: Conditioning with CYC 2 x 50mg + thiotepa 2x5mg + ATG If no cardiac manifestation: Conditioning with 4 x 50mg CYC + ATG
干预措施: Autologous stemcell transplantation with CD (cluster of differentiation) 34 selected stem cells (Drug)
Conditioning with CYC/Thiotepa/ATG
In patients with cardiac manifestations as defined in the protocol the conditioning for stem cell transplantation is changed to Cyclophosphamide (CYC), thiotepa and ATG
干预措施: Autologous stemcell transplantation with CD (cluster of differentiation) 34 selected stem cells (Drug)
结局指标
主要结局
Efficay - Overall survival
时间窗: 3 years
Number of patients that are alive after 3 years
次要结局
- Safety - Treatment related mortality(100 days)
- Progression free survival(3 years)
- Efficacy - Lung function test and Skin(3 years)
- Time to engraftment(2 months)
研究者
Joerg Henes
Dr. med. Joerg Henes
University Hospital Tuebingen