High-dose immunosuppressive therapy followed by stem cell transplantation for multiple sclerosis

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.

This study is testing if a high-dose treatment followed by stem cell transplantation can help people with multiple sclerosis who haven't had success with regular treatments.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 200 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: St. Petersburg State Pavlov Medical University (Academic / other)
• Drugs / interventions: cyclophosphamide, fludarabine
• Locations: 1 site (Saint Petersburg)
• Trial ID: NCT05832515 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the use of high-dose immunosuppressive therapy combined with autologous hematopoietic stem cell transplantation (AHSCT) in patients with multiple sclerosis (MS). The study specifically evaluates the conditioning regimen that includes fludarabine and cyclophosphamide to reduce toxicity while maintaining efficacy. Participants will be monitored for safety and effectiveness, particularly those with relapsing-remitting forms of MS who have not responded to standard treatments. The trial aims to provide insights into optimizing treatment protocols for MS patients.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-65 with relapsing-remitting MS who have experienced disease progression despite previous treatments.

Not a fit: Patients with severe cardiac or pulmonary dysfunction, or those with significant organ dysfunction, may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could offer a more effective treatment option for patients with relapsing-remitting multiple sclerosis.

How similar studies have performed: Previous studies have shown promise with similar high-dose immunosuppressive therapies for MS, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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

Where this trial is running

Saint Petersburg

• First Pavlov State Medical University of St. Petersburg — Saint Petersburg, Russia (Recruiting)

Study contacts

• Principal investigator: Ivan S Moiseev — Pavlov First Saint Petersburg State Medical University
• Study coordinator: Alexey Yu Polushin

Conditions Multiple Sclerosis; Autoimmune Diseases; AHSCT; Fludarabine