Clinical trial NCT05832515: AHSCT With Fludarabine and Cyclophosphamide Based Conditioning Regimes in Patients With Multiple Sclerosis
Official title: 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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Multiple Sclerosis
Keywords: Autoimmune Diseases
AHSCT
Fludarabine
Lead sponsor: St. Petersburg State Pavlov Medical University
Sponsor class: OTHER
First posted: 2023-04-27
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


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

Primary outcomes:
measure: Multiple sclerosis progression free survival
timeFrame: 365 days
Secondary outcomes:
measure: Cumulative incidence of mortality
timeFrame: 365 days
measure: To evaluate adverse effects after FluCy200 conditioning regimen
timeFrame: 365 days
measure: Quality of life status 1
timeFrame: 365 days
measure: Quality of life status 2
timeFrame: 365 days
measure: Quality of life status 3
timeFrame: 365 days
measure: Quality of life status 4
timeFrame: 365 days
measure: Neurological status 1
timeFrame: 365 days
measure: Immune reconstitution
timeFrame: 365 days
measure: Magnetic resonance imaging response
timeFrame: 365 days
Other outcomes:
Locations:
city: Saint Petersburg
country: Russian Federation
facility: First Pavlov State Medical University of St. Petersburg
Study officials:
affiliation: Pavlov First Saint Petersburg State Medical University
name: Ivan S Moiseev
role: PRINCIPAL_INVESTIGATOR
References: