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

NCT05832515 | Recruiting Phase 1

• 1 other identifier: FluCy_MS
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Sclerosis

Keywords

Autoimmune Diseases; AHSCT; Fludarabine

Outcome Measures

Primary Outcomes (1)

• Multiple sclerosis progression free survival

  To evaluate safety and effectiveness of immunoablative conditioning regimen FluCy200 in patients with refractory multiple sclerosis after AHSCT.

  365 days

Secondary Outcomes (9)

• Cumulative incidence of mortality

  365 days

• To evaluate adverse effects after FluCy200 conditioning regimen

  365 days

• Quality of life status 1

  365 days

• Quality of life status 2

  365 days

• Quality of life status 3

  365 days

Study Arms (1)

AHSCT: FluCy200

EXPERIMENTAL

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.

Drug: Fludarabine Phosphate for Injection

Interventions

Fludarabine Phosphate for Injection DRUG

Intravenous injection of fludarabine phosphate at a dose of 30 mg/m2 from day -5 to day -2 of immunoablative conditioning regimen.

Also known as: Fludarabine

AHSCT: FluCy200

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-65;
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• St. Petersburg State Pavlov Medical University: lead

Study Sites (1)

First Pavlov State Medical University of St. Petersburg

Saint Petersburg, 197022, Russia

RECRUITING

MeSH Terms

Conditions

Multiple Sclerosis; Autoimmune Diseases

Interventions

fludarabine phosphate; Injections; fludarabine

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Ivan S Moiseev

  Pavlov First Saint Petersburg State Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alexey Yu Polushin

CONTACT

+79118167559; alexpolushin@yandex.ru

Yury R Zalyalov

CONTACT

+79112193127; yz21@mail.ru

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice-director for science of R.M. Gorbacheva Memorial Institute of Hematology, Oncology and Transplantation

Study Record Dates

• First Submitted: April 4, 2022
• First Posted: April 27, 2023
• Study Start: October 1, 2020
• Primary Completion: October 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: May 7, 2024

Record last verified: 2024-05

Locations

RU (1)