Autologous Hematopoietic Stem Cell Transplantation for Refractory Multiple Sclerosis

Обзор

Autologous hematopoietic stem cell transplantation (aHSCT) is the only treatment for refractory autoimmune diseases capable of inducing long-term, drug-free and asymptomatic remission. Over the past two decades, aHSCT has been used to treat inflammatory autoimmune disease of the CNS. Patients with relapsing-remitting multiple sclerosis benefit from aHSCT treatment. However, a certain percentage of patients still experience recurrence 3 or 5 years after transplantation. Therefore, exploration of conditioning regimens will drive therapeutic advances in aHSCT in autoimmune diseases of the CNS.

Вмешательства

• Процедура Autologous haemopoietic stem cell transplantation
  Immuno-ablation and autologous CD34 selected hematopoietic stem cell transplantation (HSCT). Stem cell mobilization with cyclophosphamide 2g/m2 and filgrastim 10 ug/kg/d x 5 day. Stem cell collection with cobe cpectra stem cell purification with Miltenyi CliniMACS Stem cell transplant conditioning with busulphan 3.2 mg/kg ; fludarabine 30mg/m2 or cladribine 10mg ；cytarabine 1-2g/m2 or idarubicin 8mg/m2；cyclophosphamide 40mg/kg followed by CD34 selected autologous hematopoietic stem cell transp

Первичные конечные точки

• 3 year MS activity free survival [Срок оценки: 3 year follow-up post transplant]

Вторичные конечные точки (6)

• Time to MS treatment failure [Срок оценки: 3 years]
• Transplant related morbidity [Срок оценки: 3 years]
• Transplant related mortality [Срок оценки: 3 years]
• Immune reconstitution following transplant [Срок оценки: 3 years]
• Hematopoietic reconstitution following transplant [Срок оценки: 3 years]
• Imaging changes associated with the disease activity [Срок оценки: 3 years]

Критерии участия

Критерии включения

• Age 18-60 years;
• Diagnosed multiple sclerosis with relapses or progression and sustained accumulated impairment by a neurologist expert in the field;
• EDSS score of 3-6 (including 3 and 6);
• EDSS cerebellar functional score ≥ 3 or EDSS pyramidal functional score ≥3；
• Evidence of current disease activity;
• If a patient has previously received a cytotoxic agent (mitoxantrone, cyclophosphamide etc.) they must have normal bone marrow morphology and cytogenetics before being considered eligible for this study ;
• No evidence of hepatic inflammation or fibrosis;

Критерии исключения

• Patients with evidence of myelodysplasia or other non-autoimmune cytopenia;
• Patients having received a cytotoxic agent within one month of enrolling in this study;
• Patient with any active or chronic infection (herpes simplex virus, varicella-zoster virus, cytomegalovirus, EB virus, human immunodeficiency virus, hepatitis virus, syphilis, etc.);
• Patients having received a cytotoxic agent within one month of enrolling in this study;
• Patients with a malignant tumor currently or within the last 5 years;
• Patients with cardiac, renal, pulmonary, hepatic or other organ impairment;
• Patients whose life expectancy is severely limited by another conditions;
• Pregnancy or risk of pregnancy;
• Patients unable to give written informed consent in accordance with research ethics board guidelines.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Фундаментальное исследование

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT06228781 · IRB2023-YX-233-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗