ATLG Levels in Autologous HSCT for Multiple Sclerosis (ATLG-MS)
2026年6月4日 更新者：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.
調査の概要
研究の種類
観察的
入学 (推定)
20
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究連絡先
- 名前：Raffaella Greco
- 電話番号：+39 02-2643-3903
- メール：greco.raffaella@hsr.it
研究場所
-
-
Italy
-
Milan、Italy、イタリア、20132
- 募集
- IRCCS Ospedale San Raffaele
-
コンタクト：
- Raffaella Greco
- 電話番号：+39 02-2643-3903
- メール：greco.raffaella@hsr.it
-
-
参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
いいえ
サンプリング方法
非確率サンプル
調査対象母集団
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).
説明
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)
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
コホートと介入
グループ/コホート |
介入・治療 |
|---|---|
|
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).
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Investigate immune status in correlation with ATLG
時間枠：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
時間枠：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.
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Assess clinically relevant viral infections in correlation with viral specific IR
時間枠：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
時間枠：at 100 days and 1-year
|
Transplant-related mortality (TRM)
|
at 100 days and 1-year
|
|
Assessment of Progression Free Survival (PFS)
時間枠：at 1-year
|
Assessment of general HSCT outcomes (PFS)
|
at 1-year
|
|
Assessment of Overall survival (OS)
時間枠：At 1 year
|
Assessment of general HSCT outcomes - OS
|
At 1 year
|
|
neurological status- Expanded Disability Status Scale (EDSS)
時間枠：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
時間枠：at 1 year
|
neurological status - neurological progression
|
at 1 year
|
|
neurological status -No Evidence of Disease Activity
時間枠：At 1 year
|
No Evidence of Disease Activity (NEDA)
|
At 1 year
|
協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
一般刊行物
- 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.
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (実際)
2026年5月4日
一次修了 (推定)
2028年5月4日
研究の完了 (推定)
2029年5月4日
試験登録日
最初に提出
2026年6月4日
QC基準を満たした最初の提出物
2026年6月4日
最初の投稿 (実際)
2026年6月9日
学習記録の更新
投稿された最後の更新 (実際)
2026年6月9日
QC基準を満たした最後の更新が送信されました
2026年6月4日
最終確認日
2026年6月1日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- ATLG-MS
- 4332 (その他の識別子：Registro studi osservazionali)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
未定
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
いいえ
米国FDA規制機器製品の研究
いいえ
米国で製造され、米国から輸出された製品。
いいえ
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
ATLG administrationの臨床試験
-
Institute of Hematology & Blood Diseases Hospital...まだ募集していません
-
Fondazione Poliambulanza Istituto Ospedalieroわからない