AHSCT With Fludarabine and Cyclophosphamide Based Conditioning Regimes in Patients With Multiple Sclerosis

St. Petersburg State Pavlov Medical University

Status and phase: Enrolling; Phase 1

Conditions: Multiple Sclerosis

Treatments: Drug: Fludarabine Phosphate for Injection

Study type: Interventional

Funder types: Other

Identifiers

NCT05832515

FluCy_MS

Details and patient eligibility

About

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.

Enrollment: 200 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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200 participants in 1 patient group

AHSCT: FluCy200

Experimental group

Description:

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.

Treatment:

Drug: Fludarabine Phosphate for Injection