ATLG Levels in Autologous HSCT for Multiple Sclerosis (ATLG-MS)
4. juni 2026 oppdatert av: Ciceri Fabio
ATLG Levels and Immune Reconstitution Kinetics in Autologous HSCT for Multiple Sclerosis
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.
Studieoversikt
Status
Rekruttering
Intervensjon / Behandling
Studietype
Observasjonsmessig
Registrering (Antatt)
20
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiekontakt
- Navn: Raffaella Greco
- Telefonnummer: +39 02-2643-3903
- E-post: greco.raffaella@hsr.it
Studiesteder
-
-
Italy
-
Milan, Italy, Italia, 20132
- Rekruttering
- IRCCS Ospedale San Raffaele
-
Ta kontakt med:
- Raffaella Greco
- Telefonnummer: +39 02-2643-3903
- E-post: greco.raffaella@hsr.it
-
-
Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
- Voksen
- Eldre voksen
Tar imot friske frivillige
Nei
Prøvetakingsmetode
Ikke-sannsynlighetsprøve
Studiepopulasjon
The study will involve 20 MS patients, treated with autologous HSCT as standard-of-care according to guidelines and consensus recommendations. Autologous HSCT is considered a standard-of-care intervention in the following selected MS patients: RRMS who have failed to respond to one or more high-efficacy DMTs or progressive MS with superimposed inflammatory activity, or aggressive forms of MS where rapid neurological decline occurs early in the disease course.
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).
Beskrivelse
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)
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
Kohorter og intervensjoner
Gruppe / Kohort |
Intervensjon / Behandling |
|---|---|
|
Multiple Sclerosis patients treated with autologous HSCT as standard of care
The study will involve 20 Multiple Sclerosis (MS) patients, treated with autologous HSCT as standard-of-care according to guidelines and consensus recommendations.
Autologous Hematopoietic stem cell transplantation (HSCT) is considered a standard-of-care intervention in the following selected MS patients: RRMS who have failed to respond to one or more high-efficacy Disease modifying therapies (DMTs) or progressive MS with superimposed inflammatory activity, or aggressive forms of MS where rapid neurological decline occurs early in the disease course.
|
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).
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Investigate immune status in correlation with ATLG
Tidsramme: before mobilization, before conditioning, +1/3/6/12 months after HSCT.
|
Longitudinal IR monitoring (T/B/NK lymphocyte subpopulations including naïve- memory- stem/memory- regulatory subsets, cytokine profile, NFL/Macrophages) on PB
|
before mobilization, before conditioning, +1/3/6/12 months after HSCT.
|
|
Investigate immune status in correlation with ATLG
Tidsramme: before and 30' after the end of ATLG dose, day0, day1, weekly for 4 weeks.
|
Assessment of ATLG levels & kinetics
|
before and 30' after the end of ATLG dose, day0, day1, weekly for 4 weeks.
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Assess clinically relevant viral infections in correlation with viral specific IR
Tidsramme: before mobilization, +1 month after HSCT within the first year after HSCT.
|
Assessment of pathogen-specific responses (CMV specific T cells by ELISpot) and occurrence of clinically relevant viral infections (CMV, EBV; ECIL 10 guidelines).
|
before mobilization, +1 month after HSCT within the first year after HSCT.
|
|
To assess HSCT and neurological outcomes
Tidsramme: at 100 days and 1-year
|
Transplant-related mortality (TRM)
|
at 100 days and 1-year
|
|
Assessment of Progression Free Survival (PFS)
Tidsramme: at 1-year
|
Assessment of general HSCT outcomes (PFS)
|
at 1-year
|
|
Assessment of Overall survival (OS)
Tidsramme: At 1 year
|
Assessment of general HSCT outcomes - OS
|
At 1 year
|
|
neurological status- Expanded Disability Status Scale (EDSS)
Tidsramme: at 100 days, 6 months and 1-year
|
Expanded Disability Status Scale (EDSS)
|
at 100 days, 6 months and 1-year
|
|
neurological status - neurological progression
Tidsramme: at 1 year
|
neurological status - neurological progression
|
at 1 year
|
|
neurological status -No Evidence of Disease Activity
Tidsramme: At 1 year
|
No Evidence of Disease Activity (NEDA)
|
At 1 year
|
Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Publikasjoner og nyttige lenker
Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.
Generelle publikasjoner
- Sharrack B, Saccardi R, Alexander T, Badoglio M, Burman J, Farge D, Greco R, Jessop H, Kazmi M, Kirgizov K, Labopin M, Mancardi G, Martin R, Moore J, Muraro PA, Rovira M, Sormani MP, Snowden JA; European Society for Blood and Marrow Transplantation (EBMT) Autoimmune Diseases Working Party (ADWP) and the Joint Accreditation Committee of the International Society for Cellular Therapy (ISCT) and EBMT (JACIE). Autologous haematopoietic stem cell transplantation and other cellular therapy in multiple sclerosis and immune-mediated neurological diseases: updated guidelines and recommendations from the EBMT Autoimmune Diseases Working Party (ADWP) and the Joint Accreditation Committee of EBMT and ISCT (JACIE). Bone Marrow Transplant. 2020 Feb;55(2):283-306. doi: 10.1038/s41409-019-0684-0. Epub 2019 Sep 26.
- Oostenbrink LVE, Jol-van der Zijde CM, Kielsen K, Jansen-Hoogendijk AM, Ifversen M, Muller KG, Lankester AC, van Halteren AGS, Bredius RGM, Schilham MW, van Tol MJD. Differential Elimination of Anti-Thymocyte Globulin of Fresenius and Genzyme Impacts T-Cell Reconstitution After Hematopoietic Stem Cell Transplantation. Front Immunol. 2019 Mar 6;10:315. doi: 10.3389/fimmu.2019.00315. eCollection 2019.
- 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.
- 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/s41409-025-02730-y. Epub 2025 Nov 27.
- 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 multiple sclerosis: a retrospective analysis of the EBMT autoimmune diseases working party. Bone Marrow Transplant. 2025 Dec;60(12):1628-1634. doi: 10.1038/s41409-025-02715-x. Epub 2025 Sep 29.
- 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 Society for Cellular Therapy (ISCT); EBMT (JACIE). Evolution, trends, outcomes, and economics of hematopoietic stem cell transplantation in severe autoimmune diseases. Blood Adv. 2017 Dec 20;1(27):2742-2755. doi: 10.1182/bloodadvances.2017010041. eCollection 2017 Dec 26.
- 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. Bone Marrow Transplant. 2015 Sep;50(9):1262-4. doi: 10.1038/bmt.2015.132. Epub 2015 Jun 15. No abstract available.
- 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 27;9(14):11451-11464. doi: 10.18632/oncotarget.24328. eCollection 2018 Feb 20.
- 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. Epub 2019 Nov 19.
- Mueller TF. Phenotypic changes with immunosuppression in human recipients. Front Biosci. 2003 Sep 1;8:d1254-74. doi: 10.2741/1182.
- Cencioni MT, Genchi A, Brittain G, de Silva TI, Sharrack B, Snowden JA, Alexander T, Greco R, Muraro PA. Immune Reconstitution Following Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis: A Review on Behalf of the EBMT Autoimmune Diseases Working Party. Front Immunol. 2022 Feb 1;12:813957. doi: 10.3389/fimmu.2021.813957. eCollection 2021.
- Ismail A, Nitti R, Sharrack B, Badoglio M, Ambron P, Labopin M, Alexander T, Snowden JA, Greco R. ATG and other serotherapy in conditioning regimens for autologous HSCT in autoimmune diseases: a survey on behalf of the EBMT Autoimmune Diseases Working Party (ADWP). Bone Marrow Transplant. 2024 Nov;59(11):1614-1617. doi: 10.1038/s41409-024-02383-3. Epub 2024 Aug 14. No abstract available.
- Muraro PA, Mariottini A, Greco R, Burman J, Iacobaeus E, Inglese M, Snowden JA, Alexander T, Amato MP, Bo L, Boffa G, Ciccarelli O, Cohen JA, Derfuss T, Farge D, Freedman MS, Gaughan M, Heesen C, Kazmi M, Kirzigov K, Ljungman P, Mancardi G, Martin R, Mehra V, Moiola L, Saccardi R, Tintore M, Stankoff B, Sharrack B; Attendees of the ECTRIMS Focused Workshop on HSCT. Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis and neuromyelitis optica spectrum disorder - recommendations from ECTRIMS and the EBMT. Nat Rev Neurol. 2025 Mar;21(3):140-158. doi: 10.1038/s41582-024-01050-x. Epub 2025 Jan 15.
- Greco R, Ruggeri A, McLornan DP, Snowden JA, Alexander T, Angelucci E, Averbuch D, Bazarbachi A, Hazenberg MD, Kalwak K, Kenyon M, Mekelenkamp H, Neven B, Pedrazzoli P, Peric Z, Risitano AM, Sanchez-Ortega I, Ciceri F, Sureda A. Indications for haematopoietic cell transplantation and CAR-T for haematological diseases, solid tumours and immune disorders: 2025 EBMT practice recommendations. Bone Marrow Transplant. 2025 Nov;60(11):1499-1525. doi: 10.1038/s41409-025-02701-3. Epub 2025 Sep 9.
- Alexander T, Greco R. Hematopoietic stem cell transplantation and cellular therapies for autoimmune diseases: overview and future considerations from the Autoimmune Diseases Working Party (ADWP) of the European Society for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplant. 2022 Jul;57(7):1055-1062. doi: 10.1038/s41409-022-01702-w. Epub 2022 May 16.
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart (Faktiske)
4. mai 2026
Primær fullføring (Antatt)
4. mai 2028
Studiet fullført (Antatt)
4. mai 2029
Datoer for studieregistrering
Først innsendt
4. juni 2026
Først innsendt som oppfylte QC-kriteriene
4. juni 2026
Først lagt ut (Faktiske)
9. juni 2026
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
9. juni 2026
Siste oppdatering sendt inn som oppfylte QC-kriteriene
4. juni 2026
Sist bekreftet
1. juni 2026
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- ATLG-MS
- 4332 (Annen identifikator: Registro studi osservazionali)
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
UBESLUTTE
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Nei
Studerer et amerikansk FDA-regulert enhetsprodukt
Nei
produkt produsert i og eksportert fra USA
Nei
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .