ATLG Levels in Autologous HSCT for Multiple Sclerosis

Ciceri Fabio20 enrolled

Overview

This is a prospective, observational, biological, multicenter study to investigate IR profile, ATLG dynamics, main HSCT and disease outcomes in MS. This study will provide a preliminary descriptive evaluation of key study parameters, including ATLG pharmacokinetics and immune reconstitution trends, as well as an initial assessment of variability (e.g., dispersion of immunological biomarkers), to support the interpretation of results and the design of future studies. Since this is an observational study, no clinical decision will be made, and the interim analysis will not have an impact of the study conduction, and it will not be a stopping rule.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Multiple Sclerosis Autologous Hematopoietic Stem Cell Transplant ATLG

Interventions

ATLG administration

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Participant is willing and able to give informed consent for participation in the study. * Adult patients (age \>/= 18y) * Diagnosis of MS * Confirmed program of autologous HSCT according to standard EBMT indications (any conditioning regimen considered standard, BEAM or Cyclophosphamide) * ATLG (total dose 30 mg/kg over 3 days: 10 mg/kg on days -3, -2 and -1) in the conditioning regimen. Exclusion Criteria: * Subjects that did not accept to sign the informed consent. * Use of ATG. * Contraindications to HSCT procedures (including pregnancy and breast feeding, uncontrolled active infections)

Outcomes

Primary Outcomes

Investigate immune status in correlation with ATLG

Longitudinal IR monitoring (T/B/NK lymphocyte subpopulations including naïve- memory- stem/memory- regulatory subsets, cytokine profile, NFL/Macrophages) on PB

Time frame: before mobilization, before conditioning, +1/3/6/12 months after HSCT.

Investigate immune status in correlation with ATLG

Assessment of ATLG levels \& kinetics

Time frame: before and 30' after the end of ATLG dose, day0, day1, weekly for 4 weeks.

Secondary Outcomes

Assess clinically relevant viral infections in correlation with viral specific IR

Assessment of pathogen-specific responses (CMV specific T cells by ELISpot) and occurrence of clinically relevant viral infections (CMV, EBV; ECIL 10 guidelines).

Time frame: before mobilization, +1 month after HSCT within the first year after HSCT.

To assess HSCT and neurological outcomes

Transplant-related mortality (TRM)

Time frame: at 100 days and 1-year

Assessment of Progression Free Survival (PFS)

Assessment of general HSCT outcomes (PFS)

Time frame: at 1-year

Assessment of Overall survival (OS)

Assessment of general HSCT outcomes - OS

Time frame: At 1 year

neurological status- Expanded Disability Status Scale (EDSS)

Expanded Disability Status Scale (EDSS)

Time frame: at 100 days, 6 months and 1-year

neurological status - neurological progression

Time frame: at 1 year

neurological status -No Evidence of Disease Activity

No Evidence of Disease Activity (NEDA)