Novel First-line Therapies for Grade II Acute GVHD(Graft-versus-host Disease )

Официальное название

Novel First-line Therapies for Grade II Acute GVHD: a Randomized Controlled Trial

Обзор

The purpose of this study is to determine the efficacy and safety of combined Ruxolitinib With Corticosteroids as First Line Therapy for grade II acute GVHD (graft-versus-host disease )

Подробное описание

Acute graft-versus-host disease (GVHD) is treated with systemic corticosteroid immunosuppression as first line therapy. Many patients with grade II acute GVHD do not respond to primary therapy, high-dose systemic corticosteroids; therefore, survival for those patients remains particularly poor. Here we determine the efficacy and safety of combined Ruxolitinib With Corticosteroids as First Line Therapy for the Treatment of grade II acute GVHD.

Вмешательства

• Препарат Ruxolitinib
  Participants began oral administration of ruxolitinib at 5 mg QD;Methylprednisolone: 0.5mg/kg/d , iv or iv gtt for at least 5 days, then taper according to the clinical response.
• Препарат Corticosteroids
  Methylprednisolone: 2mg/kg/d , iv or iv gtt for at least 1 week, then taper according to the clinical response.

Первичные конечные точки

• Overall response rate (ORR) at Day 28 [Срок оценки: Day 28 after treatment]

Вторичные конечные точки (9)

• Six-month duration of response [Срок оценки: Six-month after treatment]
• Duration of response [Срок оценки: Day 90 after treatment]
• Nonrelapse mortality (NRM) [Срок оценки: 1 year after treatment]
• Cumulative incidence of relapse (CIR) [Срок оценки: 1 year after treatment]
• Disease-free survival (DFS) [Срок оценки: 1 year after treatment]
• Overall survival (OS) [Срок оценки: 1 year after treatment]
• GVHD-free and relapse-free survival (GRFS) [Срок оценки: 1 year after treatment]
• Recurrence of aGVHD [Срок оценки: 1 year after treatment]
• Failure-free survival [Срок оценки: 1 year after treatment]

Критерии участия

Критерии включения

• Diagnosed with hematological diseases.
• Have undergone first allogeneic hematopoietic stem cell transplantation (allo-HSCT) from any donor source using bone marrow, peripheral blood stem cells, or cord blood for hematologic malignancies.
• New onset of grade II acute GVHD or intermediate or high risk aGVHD (based on modified GVHD Glucksberg criteria) within 100 days post-transplantation.

Критерии исключения

• Recipients of second allogeneic stem cell transplant.
• Acute GVHD induced by donor lymphocyte infusion, interferon.
• Received first line aGVHD treatment before enrollment.
• Overlap GVHD syndrome.
• Pregnant or breast-feeding women.
• Pregnant or breast-feeding women.
• Serum creatinine > 2.0 mg/dL or creatinine clearance < 40 mL/min measured or calculated by Cockroft-Gault equation.
• Uncontrolled infection.
• Human immunodeficiency virus infection.
• Active hepatitis b virus, hepatitis C virus infection and need antivirus treatment.
• Subjects with evidence of relapsed primary disease, or subjects who have been treated for relapse after the allo-HSCT was performed, or graft rejection.
• Allergic history to Janus kinase inhibitors.
• Severe organ dysfunction unrelated to underlying GVHD, including:

(1)Cholestatic disorders or unresolved veno-occlusive disease of the liver (defined as persistent bilirubin abnormalities not attributable to GVHD and ongoing organ dysfunction).

(2)Clinically significant or uncontrolled cardiac disease including unstable angina, acute myocardial infarction within 6 months from Day 1 of study drug administration, New York Heart Association Class III or IV congestive heart failure, circulatory collapse requiring vasopressor or inotropic support, or arrhythmia that requires therapy.

(3)Clinically significant respiratory disease that requires mechanical ventilation support or 50% oxygen.

14.Received Janus kinase inhibitor therapy after allo-HSCT for any indication. 15.Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the subject; or interfere with interpretation of study data.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Department of Hematology, Senior Department of Hematology, The Fifth Medical Center of PLA — Пекин

Публикации

• von Bubnoff N, Ihorst G, Grishina O, Rothling N, Bertz H, Duyster J, Finke J, Zeiser R. Ruxolitinib in GvHD (RIG) study: a multicenter, randomized phase 2 trial to determine the response rate of Ruxolitinib and best available treatment (BAT) versus BAT in steroid-refractory acute graft-versus-host disease (aGvHD) (NCT02396628). BMC Cancer. 2018 Nov 19;18(1):1132. doi: 10.1186/s12885-018-5045-7. PMID 30453910
• Zeiser R, von Bubnoff N, Butler J, Mohty M, Niederwieser D, Or R, Szer J, Wagner EM, Zuckerman T, Mahuzier B, Xu J, Wilke C, Gandhi KK, Socie G; REACH2 Trial Group. Ruxolitinib for Glucocorticoid-Refractory Acute Graft-versus-Host Disease. N Engl J Med. 2020 May 7;382(19):1800-1810. doi: 10.1056/NEJMoa1917635. Epub 2020 Apr 22. PMID 32320566
• Kujawska J, Zeiser R, Gil L. Recent advances in acute gastrointestinal graft versus host disease (aGvHD): aspects of steroid-resistant disease. Ann Hematol. 2025 Feb;104(2):855-865. doi: 10.1007/s00277-024-05952-0. Epub 2024 Aug 29. PMID 39207560
• Holtan SG, Yu J, Choe HK, Paranagama D, Tang J, Naim A, Galvin J, Joachim Deeg H. Disease progression, treatments, hospitalization, and clinical outcomes in acute GVHD: a multicenter chart review. Bone Marrow Transplant. 2022 Oct;57(10):1581-1585. doi: 10.1038/s41409-022-01764-w. Epub 2022 Jul 30. PMID 35908108
• Dou L, Zhao Y, Yang J, Deng L, Wang N, Zhang X, Liu Q, Yang Y, Wei Z, Wang F, Jiao Y, Li F, Luan S, Hu L, Gao S, Liu C, Liu X, Yan J, Zhang X, Zhou F, Lu P, Liu D. Ruxolitinib plus steroids for acute graft versus host disease: a multicenter, randomized, phase 3 trial. Signal Transduct Target Ther. 2024 Oct 23;9(1):288. doi: 10.1038/s41392-024-01987-x. PMID 39438467

Идентификаторы

NCT: NCT07340723 · S2025-767-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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