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

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

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 )

Study Overview

• Status: Recruiting
• Conditions: Stem Cell Transplant Complications; GVHD,Acute
• Intervention / Treatment: Drug: Ruxolitinib; Drug: Corticosteroids

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 168
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Liping Dou, M.D., Ph.D.; Phone Number: 010-66937079; Email: lipingruirui@163.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100853
      • Recruiting
      • Department of Hematology, Senior Department of Hematology, The Fifth Medical Center of PLA General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Diagnosed with hematological diseases.
2. 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.
3. New onset of grade II acute GVHD or intermediate or high risk aGVHD (based on modified GVHD Glucksberg criteria) within 100 days post-transplantation.

Exclusion Criteria:

1. Recipients of second allogeneic stem cell transplant.
2. Acute GVHD induced by donor lymphocyte infusion, interferon.
3. Received first line aGVHD treatment before enrollment.
4. Overlap GVHD syndrome.
5. Pregnant or breast-feeding women.
6. Pregnant or breast-feeding women.
7. Serum creatinine > 2.0 mg/dL or creatinine clearance < 40 mL/min measured or calculated by Cockroft-Gault equation.
8. Uncontrolled infection.
9. Human immunodeficiency virus infection.
10. Active hepatitis b virus, hepatitis C virus infection and need antivirus treatment.
11. Subjects with evidence of relapsed primary disease, or subjects who have been treated for relapse after the allo-HSCT was performed, or graft rejection.
12. Allergic history to Janus kinase inhibitors.
13. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ruxolitinib Arm; Ruxolitinib combined with Corticosteroids	Drug: 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.; Drug: Corticosteroids; Methylprednisolone: 2mg/kg/d , iv or iv gtt for at least 1 week, then taper according to the clinical response.
Active Comparator: Comparator arm	Drug: Corticosteroids; Methylprednisolone: 2mg/kg/d , iv or iv gtt for at least 1 week, then taper according to the clinical response.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR) at Day 28	Defined as the proportion of participants demonstrating a complete response (CR), or partial response (PR).	Day 28 after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of response	Defined as the time from first response until GVHD progression or death, when all participants who are still on study complete the Day 90 visit.	Day 90 after treatment
Six-month duration of response	Defined as the time from first response until graft-versus-host disease (GVHD) progression or death. Six-month duration of response will be assessed when all participants who are still on study complete the Day 180 visit.	Six-month after treatment
Nonrelapse mortality (NRM)	NRM was defined as death from any cause without relapse. Cumulative incidence of NRM was analyzed in a competing risk framework using Gray's method.	1 year after treatment
Cumulative incidence of relapse (CIR)	Defined as the proportion of participants whose underlying malignancy relapsed.Relapse was defined as hematologic recurrence of malignancies after transplantation. Cumulative incidence of relapse was analyzed in a competing risk framework using Gray's method.	1 year after treatment
Disease-free survival (DFS)	Defined as the time from day +1 to the earliest date that a participant died, had a relapse/progression of the underlying malignancy, required additional therapy for aGVHD, or demonstrated signs or symptoms of chronic graft-versus-host disease (cGVHD).DFS will be evaluated in an intent-to-treat analysis by Kaplan Meier estimate and Log Rank test.	1 year after treatment
Overall survival (OS)	Defined as survival from day +1 until death or last follow-up. OS will be evaluated in an intent-to-treat analysis by Kaplan Meier estimate and Log Rank test. Survival will be calculated from the date of randomization.	1 year after treatment
GVHD-free and relapse-free survival (GRFS)	Defined as a composite endpoint of death from any cause, disease relapse, grade Ⅲ-Ⅳ acute GVHD, or chronic GVHD requiring systemic immunosuppression therapy.	1 year after treatment
Recurrence of aGVHD	Defined as the proportion of participants whose aGVHD relapsed.Relapse was defined as recurrence of new GVHD related symptoms after complete remission of aGVHD. Cumulative incidence of recurrence of aGVHD was analyzed in a competing risk framework using Gray's method.	1 year after treatment
Failure-free survival	Failure-free survival (FFS) refers to the time from day +1 to disease relapse or progression, non-relapse mortality, or the addition of new therapy for aGVHD.	1 year after treatment

Collaborators and Investigators

• Sponsor: Daihong Liu

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: January 5, 2026
• First Submitted That Met QC Criteria: January 5, 2026
• First Posted (Actual): January 14, 2026

Study Record Updates

• Last Update Posted (Actual): January 14, 2026
• Last Update Submitted That Met QC Criteria: January 5, 2026
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Ruxolitinib; first line therapy; acute graft-versus-host disease
• Additional Relevant MeSH Terms: Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; ruxolitinib; Adrenal Cortex Hormones
• Other Study ID Numbers: S2025-767-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data requests should be evaluated on a case-by-case basis by an independent review committee in accordance with the moderated access policy of the Data Repository Unit at the Chinese PLA General Hospital, Beijing, China.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No