Multiple SclerosisTRANSPLANTPRONCT06267781
RRMS: Disease PROgression and Myeloid Profiling After Bone Marrow TRANSPLANTation and Second Line Therapies
An observational study of Multiple Sclerosis, run by IRCCS San Raffaele at 1 site in Italy.
Trial summary
To study whether highly effective therapies can halt disease progression in people with multiple sclerosis by modulating the peripheral myeloid landscape. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Sclerosis
- How many people
- 30 participants
- Where
- 1 siteItaly
- Study dates
- 2 Sep 2022to 2 Sep 2027
- Phase
- Observational
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: A total of 30 male or female prospective patients with RRMS who, from clinical practice, may be referred for treatment with aHSCT, alemtuzumab or ocrelizumab/ofatumumab will be recruited. Treatment choice will be independent of participation in the study and should not be initiated with the aim of including the patient in the study. All patients will be required to sign an informed consent before the collection of data and biological material.
Who may be able to join
- Age ≥18 years;
- Signed written informed consent;
- A diagnosis of RRMS according to the 2017 Revisions of the McDonald Criteria;
- High clinical and magnetic resonance imaging (MRI) inflammatory disease activity (at least 2 clinical relapses, or one clinical relapse with gadolinium (Gd)- enhancing or new T2 MRI lesions at a separate time point, in the previous 12 months)
- Patients referred for pharmacological treatment with aHSCT, alemtuzumab or ocrelizumab /ofatumumab, according to clinical practice following the Italian pharmacological regulatory agency (AIFA) criteria and guidelines and recommendations from the European Society for Blood and Marrow Transplantation (EBMT) Autoimmune Diseases Working Party (ADWP) and the Joint Accreditation Committee of EBMT and ISCT (JACIE);
Who cannot join
- Diagnosis of PPMS or SPMS according to the 2017 McDonald criteria
- Known intolerances/allergies to the active substance or the excipients contained in the DMT and/or contraindications according to product information
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
IRCCS San Raffaele
Milan, 20132
Massimo Filippi, MD, 00390226433054, filippi.massimo@hsr.it
Anna A. Bellini, MD, 00390226432154, bellini.anna@hsr.it
About this study
Official title: Biomarkers of Disease PROgression and Myeloid Profiling in Patients With Relapsing Remitting Multiple Sclerosis Treated With Autologous Hematopoietic Stem Cell TRANSPLANTation and Second Line Therapies.
To study whether highly effective therapies can halt disease progression in people with multiple sclerosis by modulating the peripheral myeloid landscape.
Read the detailed description
Due to the limited availability of treatment in progressive multiple sclerosis (PMS), an in-depth analysis to better understand (1) the effect of disease-modifying therapies (DMTs) in preventing transition to secondary PMS (SPMS) and (2) the progression-related pathogenetic mechanisms, is essential. This could contribute to change the MS therapeutic perspective halting the progression independent of relapse activity putative processes, beside the prevention of relapse-associated worsening. Myeloablative autologous haematopoietic stem cell transplantation (aHSCT) in relapsing remitting multiple sclerosis (RRMS), differently from other widely used highly effective DMTs such as ocrelizumab and alemtuzumab, could modulate the myeloid activity inducing - after the depletion induced by conditioning regimen - a homeostatic expansion and enhanced immune regulation of monocytes/macrophages and dendritic cells. Currently used DMTs do not primarily target microglia/macrophage-mediated inflammation, and the effect on the abovementioned immune population could account for the advantage of aHSCT, compared to ocrelizumab and alemtuzumab, on progression free survival (PFS). Indeed, alemtuzumab and ocrelizumab achieve a long-term PFS lower than aHSCT. The results of such analyses could guide clinical decisions that will have a long-term impact, given the chronicity of the diseases, the duration of therapies, and the long-lasting effects of some treatments.
Given this premise, by evaluating n.10 consecutively recruited patients with RRMS treated with myeloablative aHSCT in comparison with patients (n.10 per group) treated with anti-cluster of differentiation (CD) 52 monoclonal antibody (alemtuzumab) and anti-CD20 monoclonal antibody (ocrelizumab or ofatumumab), the aims of this longitudinal study are the following:
Aim 1: To evaluate the impact of the studied treatments (myeloablative aHSCT, alemtuzumab and ocrelizumab/ofatumumab) on biomarkers of disease progression in MS. Since to clinically evaluate conversion to SPMS a long follow-up is required, the evaluation of progression's surrogate biomarkers (clinical, neuroradiological and biological) will allow a better and faster identification of the disease course.
Aim 2: To characterize the myeloid compartments' longitudinal changes induced by each treatment (aHSCT, alemtuzumab and ocrelizumab/ofatumumab) in the enrolled patients.
Aim 3: To explore a correlation between characteristics of the myeloid profile and surrogate endpoints of disease progression, assessing whether the treatment-induced homeostatic expansion and enhanced immune regulation of the myeloid compartment are related to surrogate endpoints of progression.
- Conditions
- Multiple Sclerosis
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| aHSCT | n.10 patients with RRMS referred for pharmacological treatment with myeloablative autologous hematopoietic stem cell transplantation (aHSCT) according to clinical practice following the Italian pharmacological regulatory agency (AIFA) criteria and guidelines and recommendations from the European Society for Blood and Marrow Transplantation (EBMT) Autoimmune Diseases Working Party (ADWP) and the Joint Accreditation Committee of EBMT and ISCT (JACIE) | |
| BCDT | n.10 patients with RRMS referred for pharmacological treatment with anti-CD20 monoclonal antibody (ocrelizumab or ofatumumab - B cell depleting therapies) according to clinical practice following the Italian pharmacological regulatory agency (AIFA) criteria. | |
| LEM | n.10 patients with RRMS referred for pharmacological treatment with anti-CD52 monoclonal antibody (alemtuzumab) according to clinical practice following the Italian pharmacological regulatory agency (AIFA) criteria. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of fading/disappearing paramagnetic rim lesions (PRLs)
Evolution of the paramagnetic rim lesions (PRLs), main biomarker of progression, evaluated longitudinally (proportion of stable vs. fading/disappearing PRLs in each group of patients)
Measured: 2 years (baseline and at 6, 12 and 24 months after study treatment )
Secondary outcomes (6)
Surrogate biomarkers of disease progression (MSFC)
Changes in multiple sclerosis functional composite score (MSFC) evaluated longitudinally
Measured: 2 years (baseline and at 6, 12 and 24 months after study treatment)
Surrogate biomarkers of disease progression (sNfL)
Changes in serum neurofilament light chain (sNfL) evaluated longitudinally
Measured: 2 years (baseline and at 6, 12 and 24 months after study treatment)
Surrogate biomarkers of disease progression (RNFL)
Changes in retinal nerve fibre layer (RNFL) thickness evaluated longitudinally
Measured: 2 years (baseline and at 6, 12 and 24 months after study treatment)
Surrogate biomarkers of disease progression (cortical lesions)
Number of new cortical lesions
Measured: 2 years (baseline and at 6, 12 and 24 months after study treatment)
Surrogate biomarkers of disease progression (atrophy)
Changes of brain volumes evaluated longitudinally
Measured: 2 years (baseline and at 6, 12 and 24 months after study treatment)
Changes in myeloid landscape
Peripheral blood myeloid line subpopulations changes induced by each therapy studied by cytofluorometric analysis
Measured: 2 years (baseline and at 3, 6, 12 and 24 months after study treatment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2024
- Study start2 Sep 2022
- Primary completion2 Sep 2027 (estimated)
- Study completion2 Sep 2027 (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.
- More trials run by IRCCS San RaffaeleThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- IRCCS San Raffaele
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Prof. Massimo Filippi, IRCCS San Raffaele
- Investigators
- Massimo Filippi, Principal investigator, IRCCS San Raffaele
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06267781
- Sponsor's protocol ID
- TRANSPLANT-PRO
- Acronym
- TRANSPLANTPRO
- Status last verified
- Feb 2024
- First submitted
- 30 Jan 2024
- Last updated
- 20 Feb 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biomarkers of Disease PROgression and Myeloid Profiling in Patients With Relapsing Remitting Multiple Sclerosis Treated With Autologous Hematopoietic Stem Cell TRANSPLANTation and Second Line Therapies.
- ClinicalTrials.gov ID
- NCT06267781
- Acronym / sponsor ID
- TRANSPLANTPRO / TRANSPLANT-PRO
- Conditions
- Multiple Sclerosis
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- IRCCS San RaffaeleUniversity, hospital or other
- Study start
- 2 Sep 2022 (actual)
- Primary completion
- 2 Sep 2027 (estimated)
- Study completion
- 2 Sep 2027 (estimated)
- First posted
- 20 Feb 2024 (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.
To study whether highly effective therapies can halt disease progression in people with multiple sclerosis by modulating the peripheral myeloid landscape.
Detailed description
Due to the limited availability of treatment in progressive multiple sclerosis (PMS), an in-depth analysis to better understand (1) the effect of disease-modifying therapies (DMTs) in preventing transition to secondary PMS (SPMS) and (2) the progression-related pathogenetic mechanisms, is essential. This could contribute to change the MS therapeutic perspective halting the progression independent of relapse activity putative processes, beside the prevention of relapse-associated worsening. Myeloablative autologous haematopoietic stem cell transplantation (aHSCT) in relapsing remitting multiple sclerosis (RRMS), differently from other widely used highly effective DMTs such as ocrelizumab and alemtuzumab, could modulate the myeloid activity inducing - after the depletion induced by conditioning regimen - a homeostatic expansion and enhanced immune regulation of monocytes/macrophages and dendritic cells. Currently used DMTs do not primarily target microglia/macrophage-mediated inflammation, and the effect on the abovementioned immune population could account for the advantage of aHSCT, compared to ocrelizumab and alemtuzumab, on progression free survival (PFS). Indeed, alemtuzumab and ocrelizumab achieve a long-term PFS lower than aHSCT. The results of such analyses could guide clinical decisions that will have a long-term impact, given the chronicity of the diseases, the duration of therapies, and the long-lasting effects of some treatments.
Given this premise, by evaluating n.10 consecutively recruited patients with RRMS treated with myeloablative aHSCT in comparison with patients (n.10 per group) treated with anti-cluster of differentiation (CD) 52 monoclonal antibody (alemtuzumab) and anti-CD20 monoclonal antibody (ocrelizumab or ofatumumab), the aims of this longitudinal study are the following:
Aim 1: To evaluate the impact of the studied treatments (myeloablative aHSCT, alemtuzumab and ocrelizumab/ofatumumab) on biomarkers of disease progression in MS. Since to clinically evaluate conversion to SPMS a long follow-up is required, the evaluation of progression's surrogate biomarkers (clinical, neuroradiological and biological) will allow a better and faster identification of the disease course.
Aim 2: To characterize the myeloid compartments' longitudinal changes induced by each treatment (aHSCT, alemtuzumab and ocrelizumab/ofatumumab) in the enrolled patients.
Aim 3: To explore a correlation between characteristics of the myeloid profile and surrogate endpoints of disease progression, assessing whether the treatment-induced homeostatic expansion and enhanced immune regulation of the myeloid compartment are related to surrogate endpoints of progression.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| aHSCT | – | –n.10 patients with RRMS referred for pharmacological treatment with myeloablative autologous hematopoietic stem cell transplantation (aHSCT) according to clinical practice following the Italian pharmacological regulatory agency (AIFA) criteria and guidelines and recommendations from the European Society for Blood and Marrow Transplantation (EBMT) Autoimmune Diseases Working Party (ADWP) and the Joint Accreditation Committee of EBMT and ISCT (JACIE) |
| BCDT | – | –n.10 patients with RRMS referred for pharmacological treatment with anti-CD20 monoclonal antibody (ocrelizumab or ofatumumab - B cell depleting therapies) according to clinical practice following the Italian pharmacological regulatory agency (AIFA) criteria. |
| LEM | – | –n.10 patients with RRMS referred for pharmacological treatment with anti-CD52 monoclonal antibody (alemtuzumab) according to clinical practice following the Italian pharmacological regulatory agency (AIFA) criteria. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- A total of 30 male or female prospective patients with RRMS who, from clinical practice, may be referred for treatment with aHSCT, alemtuzumab or ocrelizumab/ofatumumab will be recruited. Treatment choice will be independent of participation in the study and should not be initiated with the aim of including the patient in the study. All patients will be required to sign an informed consent before the collection of data and biological material.
Key inclusion criteria (5 listed)
- Age ≥18 years;
- Signed written informed consent;
- A diagnosis of RRMS according to the 2017 Revisions of the McDonald Criteria;
- High clinical and magnetic resonance imaging (MRI) inflammatory disease activity (at least 2 clinical relapses, or one clinical relapse with gadolinium (Gd)- enhancing or new T2 MRI lesions at a separate time point, in the previous 12 months)
- Patients referred for pharmacological treatment with aHSCT, alemtuzumab or ocrelizumab /ofatumumab, according to clinical practice following the Italian pharmacological regulatory agency (AIFA) criteria and guidelines and recommendations from the European Society for Blood and Marrow Transplantation (EBMT) Autoimmune Diseases Working Party (ADWP) and the Joint Accreditation Committee of EBMT and ISCT (JACIE);
Key exclusion criteria (2 listed)
- Diagnosis of PPMS or SPMS according to the 2017 McDonald criteria
- Known intolerances/allergies to the active substance or the excipients contained in the DMT and/or contraindications according to product information
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Number of fading/disappearing paramagnetic rim lesions (PRLs)
Time frame: 2 years (baseline and at 6, 12 and 24 months after study treatment )
Evolution of the paramagnetic rim lesions (PRLs), main biomarker of progression, evaluated longitudinally (proportion of stable vs. fading/disappearing PRLs in each group of patients)
6 secondary outcomes
Surrogate biomarkers of disease progression (MSFC)
Time frame: 2 years (baseline and at 6, 12 and 24 months after study treatment)
Surrogate biomarkers of disease progression (sNfL)
Time frame: 2 years (baseline and at 6, 12 and 24 months after study treatment)
Surrogate biomarkers of disease progression (RNFL)
Time frame: 2 years (baseline and at 6, 12 and 24 months after study treatment)
Surrogate biomarkers of disease progression (cortical lesions)
Time frame: 2 years (baseline and at 6, 12 and 24 months after study treatment)
Surrogate biomarkers of disease progression (atrophy)
Time frame: 2 years (baseline and at 6, 12 and 24 months after study treatment)
Changes in myeloid landscape
Time frame: 2 years (baseline and at 3, 6, 12 and 24 months after study treatment)
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 20 Feb 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.
Massimo Filippi principal investigator
IRCCS San Raffaele
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Multiple Sclerosis, run by IRCCS San Raffaele at 1 site in Italy.
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 5 inclusion and 2 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 20 Feb 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 Italy. 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.
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 Angela Genchi (+390226452846, genchi.angela@hst.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of fading/disappearing paramagnetic rim lesions (PRLs) (time frame: 2 years (baseline and at 6, 12 and 24 months after study treatment )). 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 20 Feb 2024.