Autologous Hematopoietic Stem Cell Transplantation for Refractory Multiple Sclerosis

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Procedure: Autologous haemopoietic stem cell transplantation

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Qiang Liu, M.D.,Ph.D; Phone Number: +86 15022439149; Email: qliu@tmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18-60 years;
2. Diagnosed multiple sclerosis with relapses or progression and sustained accumulated impairment by a neurologist expert in the field;
3. EDSS score of 3-6 (including 3 and 6);
4. EDSS cerebellar functional score ≥ 3 or EDSS pyramidal functional score ≥3；
5. Evidence of current disease activity;
6. 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 ;
7. No evidence of hepatic inflammation or fibrosis;

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Hematopoietic Stem Cell Transplantation; Patients will undergo stem cell transplantation for the treatment of refractory MS

Procedure: 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 transplant.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3 year MS activity free survival	The events for the primary outcome are: clinical relapse, appearance of a new or Gd-enhancing lesion on MRI, or sustained progression of EDSS score.	3 year follow-up post transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to MS treatment failure	Disease activity and disability will be assessed with clinical relapse, appearance of a new or Gd-enhancing lesion on MRI, or sustained progression of EDSS score and quality of life.	3 years
Transplant related morbidity	Rate of transplant related events.	3 years
Transplant related mortality	Rate of transplant related death.	3 years
Immune reconstitution following transplant	Rate of immune reconstitution following transplant.	3 years
Hematopoietic reconstitution following transplant	Rate of hematopoietic reconstitution following transplant.	3 years
Imaging changes associated with the disease activity	Imaging changes include: new or enlarging T2-weighted lesion count and new T1-weighted lesion count at all scans after baseline; T2-weighted lesion volume; Gd-enhanced lesion count and volume; and total volume of non-enhancing T1-weighted lesions on all MRI scans.	3 years

Collaborators and Investigators

• Sponsor: Tianjin Medical University General Hospital
• Investigators: Principal Investigator: Qiang Liu, M.D.,Ph.D, Tianjin Medical University General Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: January 19, 2024
• First Submitted That Met QC Criteria: January 19, 2024
• First Posted (Actual): January 29, 2024

Study Record Updates

• Last Update Posted (Actual): May 30, 2025
• Last Update Submitted That Met QC Criteria: May 25, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis; Sclerosis
• Other Study ID Numbers: IRB2023-YX-233-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No