ATLG Levels in Autologous HSCT for Multiple Sclerosis

Official title

ATLG Levels and Immune Reconstitution Kinetics in Autologous HSCT for Multiple Sclerosis

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.

Interventions

• Drug ATLG administration
  Patients will receive standard conditioning regimen (BEAM or cyclophosphamide) and ATLG (total dose 30 mg/kg over 3 days: 10 mg/kg on days -3, -2 and -1).

Primary outcome measures

• Investigate immune status in correlation with ATLG [Time frame: before mobilization, before conditioning, +1/3/6/12 months after HSCT.]
• Investigate immune status in correlation with ATLG [Time frame: before and 30' after the end of ATLG dose, day0, day1, weekly for 4 weeks.]

Secondary outcome measures (7)

• Assess clinically relevant viral infections in correlation with viral specific IR [Time frame: before mobilization, +1 month after HSCT within the first year after HSCT.]
• To assess HSCT and neurological outcomes [Time frame: at 100 days and 1-year]
• Assessment of Progression Free Survival (PFS) [Time frame: at 1-year]
• Assessment of Overall survival (OS) [Time frame: At 1 year]
• neurological status- 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 [Time frame: At 1 year]

Eligibility criteria

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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Case-only

Study locations

Italy · 1 center

• IRCCS Ospedale San Raffaele — Milan

Publications

• Iacobelli S; EBMT Statistical Committee. Suggestions on the use of statistical methodologies in studies of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant. 2013 Mar;48 Suppl 1:S1-37. doi: 10.1038/bmt.2012.282. PMID 23462821
• Richter J, Gagelmann N, Fischbach F, Rathje K, Pfeffer LK, Fehse B, Badbaran A, Berger SC, Krause R, Klyuchnikov E, Wolschke C, Lueck C, Ayuk F, Friese MA, Heesen C, Kroger N. Comparison of anti-human T cell globulins on immune reconstitution and early infections after autologous transplant in patients with multiple sclerosis. Bone Marrow Transplant. 2026 Feb;61(2):172-178. doi: 10.1038/s41409-025 PMID 41310182
• Greco R, Saccardi R, Ponzano M, Badoglio M, Helbig G, Smilowski M, Mariottini A, Burman J, Carlson K, Kazmi M, Muraro PA, Gabriel I, Withers B, Massey J, Varaldo R, Inglese M, Sanz J, Gil-Perotin S, Sharrack B, Roldan E, Nozzoli C, Signori A, Sormani MP, Alexander T, Snowden JA. BEAM/ATG or cyclophosphamide/ATG as conditioning regimen in autologous haemopoietic stem cell transplantation for multip PMID 41023426
• Snowden JA, Badoglio M, Labopin M, Giebel S, McGrath E, Marjanovic Z, Burman J, Moore J, Rovira M, Wulffraat NM, Kazmi M, Greco R, Snarski E, Kozak T, Kirgizov K, Alexander T, Bader P, Saccardi R, Farge D; European Society for Blood and Marrow Transplantation (EBMT) Autoimmune Diseases Working Party (ADWP); EBMT Paediatric Working Party (PWP); Joint Accreditation Committee of the International Soc PMID 29296926
• Noviello M, Forcina A, Veronica V, Crocchiolo R, Stanghellini MT, Carrabba M, Greco R, Vago L, Giglio F, Assanelli A, Carbone MR, Magnani Z, Crippa F, Corti C, Bernardi M, Peccatori J, Bordignon C, Ciceri F, Bonini C, Bondanza A. Early recovery of CMV immunity after HLA-haploidentical hematopoietic stem cell transplantation as a surrogate biomarker for a reduced risk of severe infections overall. PMID 26076126
• Retiere C, Willem C, Guillaume T, Vie H, Gautreau-Rolland L, Scotet E, Saulquin X, Gagne K, Bene MC, Imbert BM, Clemenceau B, Peterlin P, Garnier A, Chevallier P. Impact on early outcomes and immune reconstitution of high-dose post-transplant cyclophosphamide vs anti-thymocyte globulin after reduced intensity conditioning peripheral blood stem cell allogeneic transplantation. Oncotarget. 2018 Jan PMID 29545911
• Naeije L, Kariminia A, Abdossamadi S, Azadpour S, Subrt P, Kuzeljevic B, Irvine MA, Walker I, Schultz KR. Anti-Thymocyte Globulin Prophylaxis Induces a Decrease in Naive Th Cells to Inhibit the Onset of Chronic Graft-versus-Host Disease: Results from the Canadian Bone Marrow Transplant Group (CBMTG) 0801 Study. Biol Blood Marrow Transplant. 2020 Mar;26(3):438-444. doi: 10.1016/j.bbmt.2019.11.015. PMID 31756535
• Mueller TF. Phenotypic changes with immunosuppression in human recipients. Front Biosci. 2003 Sep 1;8:d1254-74. doi: 10.2741/1182. PMID 12957847

Identifiers

NCT: NCT07635693 · ATLG-MS · 4332

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗