First Line Therapy for High Risk Acute GVHD

NCT ID: NCT04061876

Last Updated: 2023-11-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

198 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-08-25

Study Completion Date

2023-06-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Acute graft-versus-host disease (aGVHD) is treated with systemic corticosteroid immunosuppression as first line therapy. Many patients with high risk aGVHD 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 High risk aGVHD.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

aGVHD Stem Cell Transplant Complications

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Ruxolitinib combined with Corticosteroids

Participants began oral administration of ruxolitinib at 5 mg QD; Methylprednisolone: 1mg/kg/d , iv or iv gtt for at leas 5 days, then taper according to the clinical response.

Group Type EXPERIMENTAL

Ruxolitinib

Intervention Type DRUG

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

Corticosteroid

Intervention Type DRUG

Methylprednisolone: 2mg/kg/d , iv or iv gtt for at least 3 days, then taper according to the clinical response. 1mg/kg/d , iv or iv gtt for at least 5 days, then taper according to the clinical response.

Corticosteroids

Methylprednisolone: 2mg/kg/d , iv or iv gtt for at least 1 week, then taper according to the clinical response.

Group Type ACTIVE_COMPARATOR

Corticosteroid

Intervention Type DRUG

Methylprednisolone: 2mg/kg/d , iv or iv gtt for at least 3 days, then taper according to the clinical response. 1mg/kg/d , iv or iv gtt for at least 5 days, then taper according to the clinical response.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Ruxolitinib

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

Intervention Type DRUG

Corticosteroid

Methylprednisolone: 2mg/kg/d , iv or iv gtt for at least 3 days, then taper according to the clinical response. 1mg/kg/d , iv or iv gtt for at least 5 days, then taper according to the clinical response.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

New Traditional

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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\~IV aGVHD or intermediate or high risk aGVHD (based on ST2, REG3a, other experimental objects) 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. absolute neutrophil count (ANC) \<0.5×10e9/L or platelet count (PLT) \< 20×10e9/L
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:

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

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.

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.
Minimum Eligible Age

14 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

LU DAOPEI MEDICAL

UNKNOWN

Sponsor Role collaborator

960th Hospital of PLA

UNKNOWN

Sponsor Role collaborator

The Second Hospital of Hebei Medical University

OTHER

Sponsor Role collaborator

The Second Affiliated Hospital of Dalian Medical University

OTHER

Sponsor Role collaborator

Air Force Military Medical University, China

OTHER

Sponsor Role collaborator

Chinese PLA General Hospital

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Daihong Liu

Director

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Daihong Liu

Role: STUDY_DIRECTOR

Chines PLA General Hospital

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Chinese PLA General Hospital

Beijing, Beijing Municipality, China

Site Status

Countries

Review the countries where the study has at least one active or historical site.

China

References

Explore related publications, articles, or registry entries linked to this study.

Kuzmina Z, Eder S, Bohm A, Pernicka E, Vormittag L, Kalhs P, Petkov V, Stary G, Nepp J, Knobler R, Just U, Krenn K, Worel N, Greinix HT. Significantly worse survival of patients with NIH-defined chronic graft-versus-host disease and thrombocytopenia or progressive onset type: results of a prospective study. Leukemia. 2012 Apr;26(4):746-56. doi: 10.1038/leu.2011.257. Epub 2011 Sep 16.

Reference Type BACKGROUND
PMID: 21926960 (View on PubMed)

Thepot S, Zhou J, Perrot A, Robin M, Xhaard A, de Latour RP, Ades L, Ribaud P, Petropoulou AD, Porcher R, Socie G. The graft-versus-leukemia effect is mainly restricted to NIH-defined chronic graft-versus-host disease after reduced intensity conditioning before allogeneic stem cell transplantation. Leukemia. 2010 Nov;24(11):1852-8. doi: 10.1038/leu.2010.187. Epub 2010 Sep 9.

Reference Type BACKGROUND
PMID: 20827288 (View on PubMed)

Levine JE, Braun TM, Harris AC, Holler E, Taylor A, Miller H, Magenau J, Weisdorf DJ, Ho VT, Bolanos-Meade J, Alousi AM, Ferrara JL; Blood and Marrow Transplant Clinical Trials Network. A prognostic score for acute graft-versus-host disease based on biomarkers: a multicentre study. Lancet Haematol. 2015 Jan;2(1):e21-9. doi: 10.1016/S2352-3026(14)00035-0. Epub 2014 Dec 23.

Reference Type BACKGROUND
PMID: 26687425 (View on PubMed)

Major-Monfried H, Renteria AS, Pawarode A, Reddy P, Ayuk F, Holler E, Efebera YA, Hogan WJ, Wolfl M, Qayed M, Hexner EO, Wudhikarn K, Ordemann R, Young R, Shah J, Hartwell MJ, Chaudhry MS, Aziz M, Etra A, Yanik GA, Kroger N, Weber D, Chen YB, Nakamura R, Rosler W, Kitko CL, Harris AC, Pulsipher M, Reshef R, Kowalyk S, Morales G, Torres I, Ozbek U, Ferrara JLM, Levine JE. MAGIC biomarkers predict long-term outcomes for steroid-resistant acute GVHD. Blood. 2018 Jun 21;131(25):2846-2855. doi: 10.1182/blood-2018-01-822957. Epub 2018 Mar 15.

Reference Type BACKGROUND
PMID: 29545329 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30453910 (View on PubMed)

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.

Reference Type DERIVED
PMID: 39438467 (View on PubMed)

Dou L, Peng B, Li X, Wang L, Jia M, Xu L, Li F, Liu D. Ruxolitinib-corticosteroid as first-line therapy for newly diagnosed high-risk acute graft versus host disease: study protocol for a multicenter, randomized, phase II controlled trial. Trials. 2022 Jun 6;23(1):470. doi: 10.1186/s13063-022-06426-2.

Reference Type DERIVED
PMID: 35668528 (View on PubMed)

Yang JJ, Peng B, Fang S, Wei Y, Wang H, Zhao YX, Qian K, Wen YN, Liu DH, Dou LP. [Kinetics of MDSC in Patients Treated Steroids-Ruxolitinib as the First Line Therapy for aGVHD]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2022 Feb;30(1):276-285. doi: 10.19746/j.cnki.issn.1009-2137.2022.01.046. Chinese.

Reference Type DERIVED
PMID: 35123640 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

S2019-177-01

Identifier Type: -

Identifier Source: org_study_id