Novel Therapies for Severe Acute GVHD (Graft-versus-host Disease)

Официальное название

Prospective Randomized Controlled Trial of Novel Therapies for Severe Acute GVHD (Graft-versus-host Disease)

Обзор

The purpose of this study is to determine the efficacy and safety of combined Ruxolitinib With Corticosteroids as First Line Therapy for the severe 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 severe 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 severe acute GVHD.

Вмешательства

• Препарат Ruxolitinib and Methylprednisolone
  Participants began oral administration of ruxolitinib at 5 mg QD; Methylprednisolone (1mg/kg)
• Препарат Methylprednisolone
  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 (8)

• Six-month duration of response [Срок оценки: Six-month after treatment]
• Ninety-day duration of response [Срок оценки: Day 90 after treatment]
• Nonrelapse mortality (NRM) [Срок оценки: 1 year after treatment]
• Cumulative incidence of relapse [Срок оценки: 1 year after treatment]
• Disease-free survival (DFS) [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 severe acute GVHD 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.
• Absolute neutrophil count (ANC) <0.5×10e9/L or platelet count (PLT) < 20×10e9/L.
• 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, the Fifth Center of Chinese PLA General Hospital — Пекин

Публикации

• Betts BC, Bastian D, Iamsawat S, Nguyen H, Heinrichs JL, Wu Y, Daenthanasanmak A, Veerapathran A, O'Mahony A, Walton K, Reff J, Horna P, Sagatys EM, Lee MC, Singer J, Chang YJ, Liu C, Pidala J, Anasetti C, Yu XZ. Targeting JAK2 reduces GVHD and xenograft rejection through regulation of T cell differentiation. Proc Natl Acad Sci U S A. 2018 Feb 13;115(7):1582-1587. doi: 10.1073/pnas.1712452115. Epu PMID 29382747
• 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
• Michonneau D, Devillier R, Keranen M, Rubio MT, Nicklasson M, Labussiere-Wallet H, Carre M, Huynh A, Viayna E, Roset M, Finzi J, Pfeiffer M, Thunstrom D, Lara N, Sabatelli L, Chevallier P, Itala-Remes M. Treatment Patterns and Clinical Outcomes of Patients with Moderate to Severe Acute Graft-Versus-Host Disease: A Multicenter Chart Review Study. Hematol Rep. 2024 May 6;16(2):283-294. doi: 10.3390/ PMID 38804281
• Mehta AK, Koreth J. Toward Improving Initial Therapy of Acute Graft Versus Host Disease. Am J Hematol. 2025 May;100 Suppl 3:40-54. doi: 10.1002/ajh.27593. Epub 2025 Feb 12. PMID 39936555
• 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: NCT07509749 · S2025-772-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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