ATLG Levels in Autologous HSCT for Multiple Sclerosis (ATLG-MS)
4 juni 2026 bijgewerkt door: 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.
Studie Overzicht
Toestand
Werving
Interventie / Behandeling
Studietype
Observationeel
Inschrijving (Geschat)
20
Contacten en locaties
In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.
Studiecontact
- Naam: Raffaella Greco
- Telefoonnummer: +39 02-2643-3903
- E-mail: greco.raffaella@hsr.it
Studie Locaties
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Italy
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Milan, Italy, Italië, 20132
- Werving
- IRCCS Ospedale San Raffaele
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Contact:
- Raffaella Greco
- Telefoonnummer: +39 02-2643-3903
- E-mail: greco.raffaella@hsr.it
-
-
Deelname Criteria
Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
- Volwassen
- Oudere volwassene
Accepteert gezonde vrijwilligers
Nee
Bemonsteringsmethode
Niet-waarschijnlijkheidssteekproef
Studie Bevolking
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).
Beschrijving
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)
Studie plan
Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.
Hoe is de studie opgezet?
Ontwerpdetails
Cohorten en interventies
Groep / Cohort |
Interventie / Behandeling |
|---|---|
|
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).
|
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Investigate immune status in correlation with ATLG
Tijdsspanne: before mobilization, before conditioning, +1/3/6/12 months after HSCT.
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Longitudinal IR monitoring (T/B/NK lymphocyte subpopulations including naïve- memory- stem/memory- regulatory subsets, cytokine profile, NFL/Macrophages) on PB
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before mobilization, before conditioning, +1/3/6/12 months after HSCT.
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Investigate immune status in correlation with ATLG
Tijdsspanne: before and 30' after the end of ATLG dose, day0, day1, weekly for 4 weeks.
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Assessment of ATLG levels & kinetics
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before and 30' after the end of ATLG dose, day0, day1, weekly for 4 weeks.
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Assess clinically relevant viral infections in correlation with viral specific IR
Tijdsspanne: before mobilization, +1 month after HSCT within the first year after HSCT.
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Assessment of pathogen-specific responses (CMV specific T cells by ELISpot) and occurrence of clinically relevant viral infections (CMV, EBV; ECIL 10 guidelines).
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before mobilization, +1 month after HSCT within the first year after HSCT.
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To assess HSCT and neurological outcomes
Tijdsspanne: at 100 days and 1-year
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Transplant-related mortality (TRM)
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at 100 days and 1-year
|
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Assessment of Progression Free Survival (PFS)
Tijdsspanne: at 1-year
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Assessment of general HSCT outcomes (PFS)
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at 1-year
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Assessment of Overall survival (OS)
Tijdsspanne: At 1 year
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Assessment of general HSCT outcomes - OS
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At 1 year
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neurological status- Expanded Disability Status Scale (EDSS)
Tijdsspanne: at 100 days, 6 months and 1-year
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Expanded Disability Status Scale (EDSS)
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at 100 days, 6 months and 1-year
|
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neurological status - neurological progression
Tijdsspanne: at 1 year
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neurological status - neurological progression
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at 1 year
|
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neurological status -No Evidence of Disease Activity
Tijdsspanne: At 1 year
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No Evidence of Disease Activity (NEDA)
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At 1 year
|
Medewerkers en onderzoekers
Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.
Sponsor
Publicaties en nuttige links
De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.
Algemene publicaties
- 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.
Studie record data
Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.
Bestudeer belangrijke data
Studie start (Werkelijk)
4 mei 2026
Primaire voltooiing (Geschat)
4 mei 2028
Studie voltooiing (Geschat)
4 mei 2029
Studieregistratiedata
Eerst ingediend
4 juni 2026
Eerst ingediend dat voldeed aan de QC-criteria
4 juni 2026
Eerst geplaatst (Werkelijk)
9 juni 2026
Updates van studierecords
Laatste update geplaatst (Werkelijk)
9 juni 2026
Laatste update ingediend die voldeed aan QC-criteria
4 juni 2026
Laatst geverifieerd
1 juni 2026
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
Andere studie-ID-nummers
- ATLG-MS
- 4332 (Andere identificatie: Registro studi osservazionali)
Plan Individuele Deelnemersgegevens (IPD)
Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?
ONBESLIST
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Nee
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
Nee
product vervaardigd in en geëxporteerd uit de V.S.
Nee
Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .