ATLG Levels in Autologous HSCT for Multiple Sclerosis (ATLG-MS)
4 juni 2026 uppdaterad 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.
Studieöversikt
Status
Rekrytering
Intervention / Behandling
Studietyp
Observationell
Inskrivning (Beräknad)
20
Kontakter och platser
Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.
Studiekontakt
- Namn: Raffaella Greco
- Telefonnummer: +39 02-2643-3903
- E-post: greco.raffaella@hsr.it
Studieorter
-
-
Italy
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Milan, Italy, Italien, 20132
- Rekrytering
- IRCCS Ospedale San Raffaele
-
Kontakt:
- Raffaella Greco
- Telefonnummer: +39 02-2643-3903
- E-post: greco.raffaella@hsr.it
-
-
Deltagandekriterier
Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.
Urvalskriterier
Åldrar som är berättigade till studier
- Vuxen
- Äldre vuxen
Tar emot friska volontärer
Nej
Testmetod
Icke-sannolikhetsprov
Studera befolkning
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).
Beskrivning
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
Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.
Hur är studien utformad?
Designdetaljer
Kohorter och interventioner
Grupp / Kohort |
Intervention / 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).
|
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Investigate immune status in correlation with ATLG
Tidsram: 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
Tidsram: 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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Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Assess clinically relevant viral infections in correlation with viral specific IR
Tidsram: 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
Tidsram: 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)
Tidsram: at 1-year
|
Assessment of general HSCT outcomes (PFS)
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at 1-year
|
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Assessment of Overall survival (OS)
Tidsram: 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)
Tidsram: 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
Tidsram: 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
Tidsram: At 1 year
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No Evidence of Disease Activity (NEDA)
|
At 1 year
|
Samarbetspartners och utredare
Det är här du hittar personer och organisationer som är involverade i denna studie.
Sponsor
Publikationer och användbara länkar
Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.
Allmänna publikationer
- 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.
Studieavstämningsdatum
Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.
Studera stora datum
Studiestart (Faktisk)
4 maj 2026
Primärt slutförande (Beräknad)
4 maj 2028
Avslutad studie (Beräknad)
4 maj 2029
Studieregistreringsdatum
Först inskickad
4 juni 2026
Först inskickad som uppfyllde QC-kriterierna
4 juni 2026
Första postat (Faktisk)
9 juni 2026
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
9 juni 2026
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
4 juni 2026
Senast verifierad
1 juni 2026
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
Andra studie-ID-nummer
- ATLG-MS
- 4332 (Annan identifierare: Registro studi osservazionali)
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