Multiple SclerosisPhase 1NCT05832515
AHSCT With Fludarabine and Cyclophosphamide Based Conditioning Regimes in Patients With Multiple Sclerosis
A Phase 1 study testing Fludarabine Phosphate for Injection in people with Multiple Sclerosis, run by St. Petersburg State Pavlov Medical University at 1 site in Russia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Fludarabine Phosphate for Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 siteRussia
- Study dates
- 1 Oct 2020to 1 Dec 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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
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- 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 locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Russia1 site, 1 recruiting
- Recruiting
First Pavlov State Medical University of St. Petersburg
Saint Petersburg, 197022
Alexey Yu Polushin, MD, +79118167559, alexpolushin@yandex.ru
Yury R Zalyalov, MD, +79112193127, yz21@mail.ru
About this study
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.
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.
Read more
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
- Being tested
- Fludarabine Phosphate for Injection
- Keywords
- Autoimmune Diseases, AHSCT, Fludarabine
- Medical subject headings
- Multiple Sclerosis, Autoimmune Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fludarabine Phosphate for InjectionDrug
Also called Fludarabine
Intravenous injection of fludarabine phosphate at a dose of 30 mg/m2 from day -5 to day -2 of immunoablative conditioning regimen.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Fludarabine Phosphate for Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Multiple sclerosis progression free survival
To evaluate safety and effectiveness of immunoablative conditioning regimen FluCy200 in patients with refractory multiple sclerosis after AHSCT.
Measured: 365 days
Secondary outcomes (9)
Cumulative incidence of mortality
Death from any cause after AHSCT
Measured: 365 days
To evaluate adverse effects after FluCy200 conditioning regimen
Toxicity based NCI CTCAE ver.5.0, including analysis of severe bacterial, fungal and viral infections incidence
Measured: 365 days
Quality of life status 1
Multiple sclerosis-specific questionnaire - HADS (Hospital Anxiety and Depression Scale) before and after AHSCT:
0-7 points - normal; 8-10 - subclinically expressed anxiety/depression; 11-21 - clinically expressed anxiety/depression.
Measured: 365 days
Quality of life status 2
Multiple sclerosis-specific questionnaire - The Short Form-36 (SF-36) before and after AHSCT: The SF-36 consists of 36 questions grouped into eight scales: physical functioning, role-physical functioning, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. The indicators of each scale are compiled in such a way that the higher the value of the indicator (from 0 to 100), the better the score on the chosen scale. Of these, two parameters are formed: the psychological and physical components of health.
Measured: 365 days
Quality of life status 3
Multiple sclerosis-specific questionnaire - Multiple Sclerosis Impact Scale (MSIS-29) before and after AHSCT:
The MSIS-29 scale consists of 29 items and includes indicators observed over the previous two weeks, including 20 of which characterize physical condition, coordination and mobility, and 9 questions reflect the patient's mental state. Answers are ranked on a 5-point Likert scale from 1 to 5 (1 = none; 2 = little; 3 = moderate; 4 = significant; 5 = very strong) in one direction.
The total score is the sum of all 29 responses and can range from 29 to 145. A higher score means a higher degree of disability. The result is assessed on a scale from 0 to 100, where a higher result means worse health.
Measured: 365 days
Quality of life status 4
Multiple sclerosis-specific questionnaire - Functional Assessment of Multiple Sclerosis (FAMS) before and after AHSCT:
FAMS Total score (range=0-176) is derived by adding: 1) Mobility (r=0-28). 2) Symptoms (r=0-28). 3) Emotional well- being (r=0-28). 4) General contentment (r=0-28). 5) Thinking and fatigue (r=0-36). 6) Family/social wellbeing (r=0-28).
Higher scores indicate better quality of life.
Measured: 365 days
Neurological status 1
Multiple sclerosis-specific questionnaire - EDSS (Expanded Disability Status Scale) before and after AHSCT:
0 points - Normal neurologic exam; 1.0-1.5 - No disability, minimal signs in one or two Functional Systems (FS); 2.0-2.5 - Minimal disability in one or two FS; 3.0-3,5 - Moderate disability in one FS, fully ambulatory; 4.0-4.5 - Fully ambulatory without aid. Able to walk without aid or rest some 500 or 300 meters; 5.0-5.5 - Ambulatory without aid or rest for about 200 or 100 meters; 6.0 - Intermittent assistance required to walk about 100 meters; 6.5 - Constant bilateral assistance required to walk about 20 meters; 7.0-7.5 - Unable to walk beyond about 5 meters or more than a few steps; 8.0 - Essentially restricted to bed, but may be out of bed itself; 8.5 - Essentially restricted to bed; 9.0 - Helpless bed patient; can communicate and eat; 9.5 - Totally helpless bed patient; unable to communicate effectively or eat/swallow; 10 - Death due to MS
Measured: 365 days
Immune reconstitution
Absolute number of CD3+, CD4+, CD8+, CD45+, CD19+ T-lymphocytes in cells/ml
Measured: 365 days
Magnetic resonance imaging response
Measured by Magnetic Resonance Disease Severity Scale (MRDSS)
Measured: 365 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2023
- Study start1 Oct 2020
- Primary completion1 Oct 2025 (estimated)
- Study completion1 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- St. Petersburg State Pavlov Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ivan S Moiseev, St. Petersburg State Pavlov Medical University
- Investigators
- Ivan S Moiseev, Principal investigator, Pavlov First Saint Petersburg State Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05832515
- Sponsor's protocol ID
- FluCy_MS
- Status last verified
- May 2024
- First submitted
- 4 Apr 2022
- Last updated
- 7 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT05832515
- Acronym / sponsor ID
- FluCy_MS
- Conditions
- Multiple Sclerosis
- Keywords
- Autoimmune Diseases, AHSCT, Fludarabine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- St. Petersburg State Pavlov Medical UniversityUniversity, hospital or other
- Study start
- 1 Oct 2020 (actual)
- Primary completion
- 1 Oct 2025 (estimated)
- Study completion
- 1 Dec 2026 (estimated)
- First posted
- 27 Apr 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AHSCT: FluCy200 | Experimental | Drug: Fludarabine Phosphate for InjectionAHSCT 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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;
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fludarabine Phosphate for InjectionAlso: FludarabineIntravenous injection of fludarabine phosphate at a dose of 30 mg/m2 from day -5 to day -2 of immunoablative conditioning regimen. | Drug | AHSCT: FluCy200 |
Primary outcome
Multiple sclerosis progression free survival
Time frame: 365 days
To evaluate safety and effectiveness of immunoablative conditioning regimen FluCy200 in patients with refractory multiple sclerosis after AHSCT.
9 secondary outcomes
Cumulative incidence of mortality
Time frame: 365 days
To evaluate adverse effects after FluCy200 conditioning regimen
Time frame: 365 days
Quality of life status 1
Time frame: 365 days
Quality of life status 2
Time frame: 365 days
Quality of life status 3
Time frame: 365 days
Quality of life status 4
Time frame: 365 days
Neurological status 1
Time frame: 365 days
Immune reconstitution
Time frame: 365 days
Magnetic resonance imaging response
Time frame: 365 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ivan S Moiseev principal investigator
Pavlov First Saint Petersburg State Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Fludarabine Phosphate for Injection in people with Multiple Sclerosis, run by St. Petersburg State Pavlov Medical University at 1 site in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 7 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Alexey Yu Polushin (+79118167559, alexpolushin@yandex.ru), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Multiple sclerosis progression free survival (time frame: 365 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2024.