Trial of the Efficacy and Safety of High-dose Immunosuppressive Therapy Based on Fludarabine and Cyclophosphamide-containing Conditioning Regimen Followed by Autologous Hematopoietic Stem Cell Transplantation in Patients With Multiple Sclerosis.
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Multiple sclerosis progression free survival
研究概览
简要总结
One of the possible options for the treatment of MS at present is a high-dose immunosuppressive therapy followed by autologous hematopoietic stem cell transplantation (HIST-AHSCT), which is a highly effective treatment for patients with relapsing-remitting MS.
This method of MS treatment was introduced in 1997. Significant complications and mortality associated with HIST-ATHSC is an obstacle to broad use of this method. The risk is even greater in patients with advanced disease, long duration of previous treatment and aggressive forms of MS.
Despite toxicity certain progressive cases of MS are still an indication for HIST-autoHSCT.
Most commonly used conditioning regimens for multiple sclerosis include high-dose cyclophosphamide. One of the options to reduce cyclophosphamide-related toxicity and dose is addition of fludarabine. Fludarabine is a cytostatic drug, an antimetabolite from the group of purine antagonists. It has a pronounced immunosuppressive activity and no overlapping toxicity with cyclophosphamide. The study will evaluate the safety and efficacy of this combination.
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
- •Age 18-65;
- •1.0-6.5 points on the EDSS scale (for MS);
- •Length of illness - any;
- •Disease progression during the last 6 months while taking drugs of 1st and 2nd lines;
- •An established and confirmed diagnosis of an autoimmune disease in the previous stages of treatment;
- •Ineffectiveness, inaccessibility or intolerance of Disease-Modifying Therapies;
- •Relapse after AHSCT.
- •Absence of severe concomitant somatic pathology;
- •Left ventricular injection fraction > 50%;
- •Karnofsky Performance Score (KPS) > 30%;
- •The ability to take oral medications;
- •Life expectancy is more than 1 month;
- •Signed informed consent of the patient or legal representatives.
排除标准
- •Moderate or severe cardiac dysfunction, left ventricular ejection fraction <50%
- •Moderate or severe decrease in pulmonary function, FEV1 <70% or DLCO<70% of predicted
- •Respiratory distress >grade I
- •Severe organ dysfunction: AST or ALT >5 upper normal limits, bilirubin >1.5 upper normal limits, creatinine >2 upper normal limits
- •Creatinine clearance < 60 mL/min
- •Uncontrolled bacterial or fungal infection at the time of enrollment
- •Requirement for vasopressor support at the time of enrollment
- •Karnofsky performans status <30%
- •Pregnancy
- •Somatic or psychiatric disorder making the patient unable to sign informed consent
研究组 & 干预措施
AHSCT: FluCy200
AHSCT with reduced intensity condition regimen (RIC):
cyclophosphamide intravenously at a dose of 50 mg/kg/day from -5 to day -2 inclusive; fludarabine intravenously at a dose of 30 mg/m2 from -5 to day -2 inclusive. Immunotherapy: ATG - ATGAM intravenously 20 mg/kg from -3 to -1 or Thymoglobulin 2.5 mg/kg from -3 to -1 day.
Also, within the framework of immunotherapy, instead of ATG, it is allowed to use anti-B-cell therapy - Rituximab 500 mg / m2 per day +12 AHSCT.
干预措施: Fludarabine Phosphate for Injection (Drug)
结局指标
主要结局
Multiple sclerosis progression free survival
时间窗: 365 days
To evaluate safety and effectiveness of immunoablative conditioning regimen FluCy200 in patients with refractory multiple sclerosis after AHSCT.
次要结局
- Quality of life status 1(365 days)
- Immune reconstitution(365 days)
- Cumulative incidence of mortality(365 days)
- To evaluate adverse effects after FluCy200 conditioning regimen(365 days)
- Quality of life status 2(365 days)
- Quality of life status 3(365 days)
- Quality of life status 4(365 days)
- Neurological status 1(365 days)
- Magnetic resonance imaging response(365 days)
研究者
Ivan S Moiseev
Vice-director for science of R.M. Gorbacheva Memorial Institute of Hematology, Oncology and Transplantation
St. Petersburg State Pavlov Medical University