Clinical Study on CD20 Monoclonal Antibody for Preventing Early EB Virus Activation After Allogeneic Hematopoietic Stem Cell Transplantation
Efficacy and Safety of B-cell Clearance in Preventing Early Epstein-Barr Virus Activation After Allogeneic Hematopoietic Stem Cell Transplantation: A Multicenter, Prospective, Randomized Controlled Clinical Study
The main purpose of this study is to evaluate the preventive effect and safety of CD20 monoclonal antibody clearing B cells on EBV activation 180 days after allogeneic hematopoietic stem cell transplantation. The study will also observe the effects of this strategy on EBV-PTLD, CMV reactivation, hematopoietic reconstruction, acute and chronic graft-versus-host disease (GVHD), non recurrent death, recurrence, survival, and post transplant immune reconstruction.
In this study, CD20 monoclonal antibody was used for the prevention of EBV activation after transplantation, which is an investigational prophylactic drug/beyond the indications stated in the instructions. The research doctor will explain the relevant basis, potential benefits, and potential risks to you during the informed consent process.
The research subjects were patients who received their first allogeneic hematopoietic stem cell transplantation in each enrolled transplantation center. After evaluating the inclusion and exclusion criteria and signing the informed consent form, they were randomly divided into an experimental group and a control group at a 1:1 ratio. The experimental group received prophylactic CD20 monoclonal antibody treatment (dose of 375mg/m2, intravenous application, once) 5 days after transplantation; If medication cannot be administered on time due to special clinical circumstances, it can be completed within 5 to 30 days after transplantation. The control group did not receive prophylactic CD20 monoclonal antibody within 30 days after transplantation, and EBV-DNA, CMV-DNA, and transplant related complications were monitored according to the routine procedures of the center. All subjects were followed up according to the protocol until 2 years after transplantation or death/loss to follow-up/withdrawal of informed consent. Primary endpoint evaluation will be conducted 180 days after transplantation, and continuous collection of PTLD, CMV reactivation, hematopoietic reconstruction, etc. will be conducted GVHD、 Data on recurrence, survival, safety, and immune reconstitution. Among them, allogeneic hematopoietic stem cell transplantation, routine blood routine/liver and kidney function tests, EBV-DNA/CMV-DNA monitoring, infection and GVHD management are procedures that need to be performed for diagnosis and treatment; Randomized grouping, prophylactic CD20 monoclonal antibody administration in the experimental group, data collection, and protocol specified follow-up are the relevant procedures of this study.
A tanulmány áttekintése
Állapot
Beavatkozás / kezelés
Tanulmány típusa
Beiratkozás (Becsült)
Fázis
- 2. fázis
- 3. fázis
Kapcsolatok és helyek
Tanulmányi kapcsolat
- Név: JIA CHEN
- Telefonszám: +86 051267976801
- E-mail: drchenjia@163.com
Tanulmányi helyek
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Beijing, Kína, 100000
- Még nincs toborzás
- Peking University People's Hospita
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Chongqing, Kína, 400000
- Még nincs toborzás
- The Second Affiliated Hospital of the Third Military Medical University
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Shanghai, Kína, 200000
- Még nincs toborzás
- Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
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Suzhou, Kína, 215000
- Toborzás
- The first Affiliated Hospital of Soochow University
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Kapcsolatba lépni:
- Jia Chen
- Telefonszám: 86+052167976801
- E-mail: drchenjia@163.com
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Anhui
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Hefei, Anhui, Kína, 230000
- Még nincs toborzás
- Anhui Provincial Hospital
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Henan
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Zhengzhou, Henan, Kína, 450000
- Még nincs toborzás
- The First Affiliated Hospital of Zhengzhou University School of Medicine
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Jiangsu
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Huai'an, Jiangsu, Kína, 223200
- Még nincs toborzás
- Huai'an Second People's Hospital
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Nanjing, Jiangsu, Kína, 210000
- Még nincs toborzás
- Jiangsu Provincial People's Hospital
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Xuzhou, Jiangsu, Kína, 221000
- Még nincs toborzás
- Xuzhou Medical University Affiliated Hospital
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Zhejiang
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Hangzhou, Zhejiang, Kína, 310000
- Még nincs toborzás
- The First Affiliated Hospital of Zhejiang University School of Medicine
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Részvételi kritériumok
Jogosultsági kritériumok
Tanulmányozható életkorok
Egészséges önkénteseket fogad
Tanulmányozható nemek
Leírás
Inclusion Criteria:
- 1) Age range of 14-70 years old (including threshold), gender not limited; 2) Receiving allogeneic hematopoietic stem cell transplantation for the first time; 3) Accept allogeneic hematopoietic stem cell transplantation with pre-treatment regimen containing ATG (total dose ≥ 4.5mg/kg), or determine by the researcher to be a high-risk transplant population for EBV reactivation; 4) At the time of enrollment, there were no uncontrolled severe infections, shock, severe organ failure, or other intolerance to the study treatment; 5) Expected to complete at least 180 days of follow-up for the primary endpoint, and the researcher's assessment of compliance is good; 6) The subject voluntarily signs the informed consent form; Individuals under the age of 18 are required to have their legal guardian sign an informed consent form and obtain their informed consent/consent expression if their understanding ability allows.
Exclusion Criteria:
- 1) Previously used CD20 monoclonal antibody or known to have allergic reactions to its excipients; 2) Secondary transplantation; 3) Previous history of EB virus infection related hemophilic cell syndrome, lymphoma, and other diseases; 4) EBV activation that meets the protocol definition has occurred within the 6 months prior to joining the group; 5) Patients who have received B-cell targeted therapy for any reason within the first 6 months of enrollment, including anti B-cell antibodies, B-cell antibody conjugates, BTK inhibitors, and B-cell targeted CAR-T cell therapy such as CD19; 6) There are uncontrolled infections; 7) Severe liver and kidney dysfunction, heart and lung dysfunction; 8) Those who cannot understand or comply with the research protocol or cannot sign the informed consent form; 9) The researchers believe that the patient has other circumstances that are not suitable for participating in this study.
Tanulási terv
Hogyan készül a tanulmány?
Tervezési részletek
- Elsődleges cél: Megelőzés
- Kiosztás: Véletlenszerűsített
- Beavatkozó modell: Párhuzamos hozzárendelés
- Maszkolás: Nincs (Open Label)
Fegyverek és beavatkozások
Résztvevő csoport / kar |
Beavatkozás / kezelés |
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Kísérleti: Kísérleti csoport
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The experimental group will receive prophylactic CD20 monoclonal antibody treatment (dose of 375mg/m2, intravenous application, once) 5 days after transplantation; If medication cannot be administered on time due to special clinical circumstances, it can be completed within 5 to 30 days after transplantation. |
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Nincs beavatkozás: Control group
The control group won't receive prophylactic CD20 monoclonal antibody within 30 days after transplantation, and EBV-DNA, CMV-DNA, and transplant related complications will be monitored according to the routine procedures of the center. |
Mit mér a tanulmány?
Elsődleges eredményintézkedések
Eredménymérő |
Időkeret |
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EBV activation rate
Időkeret: 180 days after transplantation
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180 days after transplantation
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Együttműködők és nyomozók
Publikációk és hasznos linkek
Általános kiadványok
- Zhang S, Ji Q, Wang Q, Hu S. Prophylactic rituximab administered on day -1 during conditioning significantly reduces early ebv reactivation in pediatric allogeneic hsct: Real-world evidence from a propensity-matched cohort of 834 patients. Blood. 2025;146:5988-5988
- Dominietto A, Tedone E, Soracco M, Bruno B, Raiola AM, Van Lint MT, Geroldi S, Lamparelli T, Galano B, Gualandi F, Frassoni F, Bacigalupo A. In vivo B-cell depletion with rituximab for alternative donor hemopoietic SCT. Bone Marrow Transplant. 2012 Jan;47(1):101-6. doi: 10.1038/bmt.2011.28. Epub 2011 Apr 4.
- Burns DM, Rana S, Martin E, Nagra S, Ward J, Osman H, Bell AI, Moss P, Russell NH, Craddock CF, Fox CP, Chaganti S. Greatly reduced risk of EBV reactivation in rituximab-experienced recipients of alemtuzumab-conditioned allogeneic HSCT. Bone Marrow Transplant. 2016 Jun;51(6):825-32. doi: 10.1038/bmt.2016.19. Epub 2016 Feb 22.
- Launspach M, Temel D, Ohlendorf E, Zirngibl F, Materne B, Oevermann L, Deubzer HE, Henssen AG, Kunkele A, Hundsdorfer P, Bernuth HV, Pruss A, Eggert A, Stackelberg AV, Lang P, Schulte JH. Rituximab therapy after pediatric hematopoietic stem cell transplantation can cause prolonged B-cell impairment and increases the risk for infections - a retrospective matched cohort study. Haematologica. 2023 Jan 1;108(1):267-272. doi: 10.3324/haematol.2022.281134. No abstract available.
- Stocker N, Labopin M, Boussen I, Paccoud O, Bonnin A, Malard F, Amiel C, Gozlan J, Battipaglia G, Dulery R, Giannotti F, Ruggeri A, Gaugler B, Mohty M, Brissot E. Pre-emptive rituximab treatment for Epstein-Barr virus reactivation after allogeneic hematopoietic stem cell transplantation is a worthwhile strategy in high-risk recipients: a comparative study for immune recovery and clinical outcomes. Bone Marrow Transplant. 2020 Mar;55(3):586-594. doi: 10.1038/s41409-019-0699-6. Epub 2019 Sep 27.
- Heslop HE. How I treat EBV lymphoproliferation. Blood. 2009 Nov 5;114(19):4002-8. doi: 10.1182/blood-2009-07-143545. Epub 2009 Sep 1.
- Papalexandri A, Gavriilaki E, Vardi A, Kotsiou N, Demosthenous C, Constantinou N, Touloumenidou T, Zerva P, Kika F, Iskas M, Batsis I, Mallouri D, Yannaki E, Anagnostopoulos A, Sakellari I. Pre-Emptive Use of Rituximab in Epstein-Barr Virus Reactivation: Incidence, Predictive Factors, Monitoring, and Outcomes. Int J Mol Sci. 2023 Nov 7;24(22):16029. doi: 10.3390/ijms242216029.
- Styczynski J, van der Velden W, Fox CP, Engelhard D, de la Camara R, Cordonnier C, Ljungman P; Sixth European Conference on Infections in Leukemia, a joint venture of the Infectious Diseases Working Party of the European Society of Blood and Marrow Transplantation (EBMT-IDWP), the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer (EORTC-IDG), the International Immunocompromised Host Society (ICHS) and the European Leukemia Net (ELN). Management of Epstein-Barr Virus infections and post-transplant lymphoproliferative disorders in patients after allogeneic hematopoietic stem cell transplantation: Sixth European Conference on Infections in Leukemia (ECIL-6) guidelines. Haematologica. 2016 Jul;101(7):803-11. doi: 10.3324/haematol.2016.144428.
- Huang J, Pan Z, Wang L, Zhang Z, Huang J, Jiang C, Cai G, Yin T. Early T-cell reconstitution predicts risk of EBV reactivation after allogeneic hematopoietic stem cell transplantation. Clin Exp Med. 2024 Jan 27;24(1):22. doi: 10.1007/s10238-023-01270-3.
- Styczynski J, Gil L, Tridello G, Ljungman P, Donnelly JP, van der Velden W, Omar H, Martino R, Halkes C, Faraci M, Theunissen K, Kalwak K, Hubacek P, Sica S, Nozzoli C, Fagioli F, Matthes S, Diaz MA, Migliavacca M, Balduzzi A, Tomaszewska A, Camara Rde L, van Biezen A, Hoek J, Iacobelli S, Einsele H, Cesaro S; Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation. Response to rituximab-based therapy and risk factor analysis in Epstein Barr Virus-related lymphoproliferative disorder after hematopoietic stem cell transplant in children and adults: a study from the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation. Clin Infect Dis. 2013 Sep;57(6):794-802. doi: 10.1093/cid/cit391. Epub 2013 Jun 13.
- Zhen S, Liu L, Zhang X, Wang J, Sun J, Liang C, Cao W, Wei J, Zhai W, Chen X, Ma Q, Zhang R, Yang D, He Y, Pang A, Han M, Jiang E, Feng S. Increased Epstein-Barr virus reactivation but similar incidence of post-transplant lymphoproliferative disorders due to pre-emptive rituximab therapy following allogeneic hematopoietic stem cell transplantation in the letermovir era for cytomegalovirus prophylaxis. Bone Marrow Transplant. 2025 May;60(5):721-724. doi: 10.1038/s41409-025-02542-0. Epub 2025 Mar 3. No abstract available.
- Kimura H, Ito Y, Suzuki R, Nishiyama Y. Measuring Epstein-Barr virus (EBV) load: the significance and application for each EBV-associated disease. Rev Med Virol. 2008 Sep-Oct;18(5):305-19. doi: 10.1002/rmv.582.
- Walker I, Panzarella T, Couban S, Couture F, Devins G, Elemary M, Gallagher G, Kerr H, Kuruvilla J, Lee SJ, Moore J, Nevill T, Popradi G, Roy J, Schultz KR, Szwajcer D, Toze C, Foley R; Canadian Blood and Marrow Transplant Group. Pretreatment with anti-thymocyte globulin versus no anti-thymocyte globulin in patients with haematological malignancies undergoing haemopoietic cell transplantation from unrelated donors: a randomised, controlled, open-label, phase 3, multicentre trial. Lancet Oncol. 2016 Feb;17(2):164-173. doi: 10.1016/S1470-2045(15)00462-3. Epub 2015 Dec 24.
Tanulmányi rekorddátumok
Tanulmány főbb dátumok
Tanulmány kezdete (Becsült)
Elsődleges befejezés (Becsült)
A tanulmány befejezése (Becsült)
Tanulmányi regisztráció dátumai
Először benyújtva
Először nyújtották be, amely megfelel a minőségbiztosítási kritériumoknak
Első közzététel (Tényleges)
Tanulmányi rekordok frissítései
Utolsó frissítés közzétéve (Tényleges)
Az utolsó frissítés elküldve, amely megfelel a minőségbiztosítási kritériumoknak
Utolsó ellenőrzés
Több információ
A tanulmányhoz kapcsolódó kifejezések
Kulcsszavak
További vonatkozó MeSH feltételek
Egyéb vizsgálati azonosító számok
- CD20antiEBV
Terv az egyéni résztvevői adatokhoz (IPD)
Tervezi megosztani az egyéni résztvevői adatokat (IPD)?
Gyógyszer- és eszközinformációk, tanulmányi dokumentumok
Egy amerikai FDA által szabályozott gyógyszerkészítményt tanulmányoz
Egy amerikai FDA által szabályozott eszközterméket tanulmányoz
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