RRMS: Disease PROgression and Myeloid Profiling After Bone Marrow TRANSPLANTation and Second Line Therapies

NCT06267781 | Recruiting

• 1 other identifier: TRANSPLANT-PRO
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

To study whether highly effective therapies can halt disease progression in people with multiple sclerosis by modulating the peripheral myeloid landscape.

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• 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)

  2 years (baseline and at 6, 12 and 24 months after study treatment )

Secondary Outcomes (6)

• Surrogate biomarkers of disease progression (MSFC)

  2 years (baseline and at 6, 12 and 24 months after study treatment)

• Surrogate biomarkers of disease progression (sNfL)

  2 years (baseline and at 6, 12 and 24 months after study treatment)

• Surrogate biomarkers of disease progression (RNFL)

  2 years (baseline and at 6, 12 and 24 months after study treatment)

• Surrogate biomarkers of disease progression (cortical lesions)

  2 years (baseline and at 6, 12 and 24 months after study treatment)

• Surrogate biomarkers of disease progression (atrophy)

  2 years (baseline and at 6, 12 and 24 months after study treatment)

Study Arms (3)

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.

Eligibility Criteria

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

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.

You may qualify if:

• 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);

You may not qualify if:

• 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

Sponsors & Collaborators

• IRCCS San Raffaele: lead

Study Sites (1)

IRCCS San Raffaele

Milan, 20132, Italy

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

We will collect the following sample from enrolled patients with RRMS: -Peripheral blood in Ethylenediamine tetraacetic acid (EDTA) at baseline and at 3, 6, 12 and 24 months after the treatment's initiation. In patients treated with aHSCT we will collect also a blood sample obtained after the stem cells mobilization (collected the same day of stem cells apheresis) and, when available, advanced material from autologous graft infusion.

MeSH Terms

Conditions

Multiple Sclerosis

Condition Hierarchy (Ancestors)

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

Study Officials

• Massimo Filippi

  IRCCS San Raffaele

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Angela Genchi

CONTACT

+390226452846; genchi.angela@hst.it

Lucia Moiola

CONTACT

+390226452931; moiola.lucia@hsr.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 30, 2024
• First Posted: February 20, 2024
• Study Start: September 2, 2022
• Primary Completion (Estimated): September 2, 2027
• Study Completion (Estimated): September 2, 2027
• Last Updated: February 20, 2024

Record last verified: 2024-02

Locations

IT (1)