Steroids Combined With Ruxolitinib as First-Line Therapy for Grade II Acute Graft-versus-Host Disease

An Exploratory Clinical Study of Low-Dose Steroids Combined With Ruxolitinib as First-Line Therapy for Grade II Acute Graft-versus-Host Disease

This study aims to evaluate the efficacy and safety of low-dose corticosteroids combined with ruxolitinib in the treatment of grade II acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation.

Study Overview

• Status: Active, not recruiting
• Conditions: Acute Graft-versus-host Disease
• Intervention / Treatment: Drug: steroids 、ruxolitinib

Detailed Description

Allogeneic hematopoietic stem cell transplantation (hereinafter referred to as transplantation) is the most effective and even the only curative approach for malignant hematologic diseases. Over the past decade, the cure rate for acute leukemia using transplants from HLA-matched sibling donors has reached 50%-75%. Although transplantation techniques have been continuously improving, the development of graft-versus-host disease (GVHD) after transplantation remains one of the most significant and severe complications, particularly acute GVHD (aGVHD). It reduces the success rate of transplantation and post-transplant disease-free survival, and is also one of the leading causes of non-relapse mortality (NRM). Acute GVHD typically occurs within the first 100 days post-transplant, with an incidence of 35% to 64%, and a mortality rate of 15% to 40% among allogeneic transplant recipients. Despite advances in transplantation techniques and GVHD prophylaxis in recent years, the incidence of acute GVHD remains as high as 30% to 60%, and treatment outcomes remain unsatisfactory. Among these, grade II acute GVHD, although less severe than grades III and IV, has a high incidence, a tendency to progress to severe GVHD, and often leads to long-term dependence on immunosuppressive therapy, imposing a heavy medical burden on patients.

Currently, the standard first-line therapy for grade II acute GVHD is systemic corticosteroids. However, approximately 40% of patients progress to severe (grade III-IV) acute GVHD, leading to a significant increase in non-relapse mortality (1-year overall mortality reaching 35.2%). Long-term high-dose corticosteroid therapy not only readily causes side effects such as infections and metabolic disorders, but also results in treatment failure or steroid dependence in up to 44.4% of patients. Nevertheless, there is currently no standard second-line treatment option for patients with steroid-refractory acute GVHD, and commonly used combination strategies lack robust evidence-based support. Therefore, there is an urgent need to explore more effective and safer early intervention strategies for the treatment of grade II acute GVHD.

In recent years, ruxolitinib (a JAK inhibitor) has brought new hope for the treatment of acute GVHD. Ruxolitinib is a selective JAK1/2 inhibitor that has been approved for the treatment of steroid-refractory acute GVHD. Studies have shown that in the early stage of GVHD, neutrophils migrate to mesenteric lymph nodes and promote disease progression, and ruxolitinib can effectively inhibit this process while reducing MHC-II expression, thereby blocking the early pathogenesis of GVHD. Furthermore, hyperactivation of the JAK-STAT signaling pathway exacerbates GVHD, and early intervention with ruxolitinib may prevent disease progression and reduce the need for second-line therapy. Additionally, ruxolitinib can enhance the therapeutic effect of corticosteroids on T cells by modulating the balance of apoptotic factors to overcome steroid resistance.

In summary, the occurrence of acute GVHD is one of the most important and severe complications after allogeneic hematopoietic stem cell transplantation, reducing transplant success rates and post-transplant disease-free survival. Grade II acute GVHD has a high incidence, a tendency to progress to severe disease, and long-term steroid dependence leads to complications such as infections and metabolic disorders, severely affecting patients' quality of life and transplant outcomes. Currently, approximately 40% of patients receiving standard first-line therapy (systemic corticosteroids) progress to grade III-IV aGVHD, and the rate of steroid resistance or dependence is as high as 44.4%. Therefore, more effective early intervention strategies are urgently needed for patients with grade II GVHD. We plan to conduct a prospective, randomized, single-arm study in patients undergoing allogeneic hematopoietic stem cell transplantation to explore a new treatment strategy for grade II acute GVHD. By introducing an innovative regimen of "ruxolitinib combined with corticosteroids", we aim to prospectively and randomly observe the therapeutic efficacy and safety of low-dose corticosteroids combined with ruxolitinib in patients with grade II acute GVHD, with the goal of improving the treatment response rates, reducing the dose and duration of corticosteroid use, and decreasing the risk of disease progression and long-term complications. This study is expected not only to improve the prognosis of patients with grade II acute GVHD and increase the success rate of transplantation, but also to drive innovative advances in the field of acute GVHD therapy.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100853
      • Chinese PLA General Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 1.Patients with malignant hematologic diseases eligible for allogeneic hematopoietic stem cell transplantation, including MDS-RAEB, acute leukemia, and chronic phase of CML.

  2.Availability of an HLA-matched sibling donor, unrelated donor, or haploidentical donor.

  3.Age ≥ 14 years. 4.Liver function: ALT and AST ≤ 2.5 × upper limit of normal (ULN), total bilirubin ≤ 2 × ULN.

  5.Renal function: serum creatinine ≤ ULN. 6.Absence of uncontrolled infection or severe psychiatric/psychological disorders.

  7.Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2. 8.Signed informed consent. 9.Diagnosis of grade II acute GVHD as assessed by the modified Glucksberg grading criteria for acute GVHD.

Exclusion Criteria:

• 1.Absence of an allogeneic donor. 2.Pregnancy of either the donor or the recipient. 3.Presence of psychiatric disorders or other conditions that preclude compliance with the study protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group; Patients with grade II acute GVHD who receive low-dose steroids plus ruxolitinib as first-line treatment	Drug: steroids 、ruxolitinib; Patients with acute grade II GVHD are treated with a combination of methylprednisolone (0.5 mg/kg/day) and ruxolitinib.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Graft-Versus-Host Disease-Free, Relapse-Free Survival	Graft-versus-host disease-free, relapse-free survival (GRFS) refers to the time from the start of treatment (or from transplantation) to the first occurrence of any of the following events: grade III-IV acute graft-versus-host disease (aGVHD), chronic graft-versus-host disease (cGVHD) requiring systemic immunosuppressive therapy, disease relapse or progression, or death from any cause.	1 years after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival (OS)	Overall survival (OS) refers to the time from the start of treatment to the death of the patient for any reason.	2 years after treatment
Overall response rate	Overall response rate (ORR) for GVHD at day 28 post treatment	28 day after treatment
Failure-free survival (FFS)	Failure-free survival (FFS) refers to the time from the start of treatment to the first occurrence of treatment failure, including lack of response, disease progression, relapse, or death from any cause.	2 years after treatment
Transplant-related mortality (TRM)	Transplant-related mortality (TRM) refers to death occurring from causes other than disease relapse, such as toxicity, infection, or organ failure, after hematopoietic stem cell transplantation.	2 years after treatment
disease free survival (DFS)	Disease free survival (DFS) refers to the time from treatment to the first lymphoma recurrence.	2 years after treatment
Overall response rate (ORR) for GVHD at day 7 post treatment	Overall response rate (ORR) for GVHD at day 7 post treatment refers to the proportion of patients achieving a complete or partial response of GVHD at day 7 after the start of treatment.	7 day after treatment
Incidence of steroid-refractory GVHD	Incidence of steroid-refractory GVHD refers to the proportion of patients who fail to	2 years after treatment
Cumulative incidence of chronic GVHD	Cumulative incidence of chronic GVHD refers to the probability of developing chronic graft-versus-host disease after transplantation, considering death as a competing event.	2 years after treatment
recurrence rate	The recurrence rate refers to the proportion of transplant patients who experience recurrence after receiving treatment.	2 years after treatment

Collaborators and Investigators

• Sponsor: Daihong Liu
• Investigators: Study Chair: Dai-Hong Liu, Dr., Chinese PLA General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2025
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2027

Study Registration Dates

• First Submitted: May 4, 2026
• First Submitted That Met QC Criteria: May 4, 2026
• First Posted (Actual): May 8, 2026

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: S2026-159-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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