NCT04061876

Brief Summary

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 )

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
198

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Aug 2019

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 17, 2019

Completed
3 days until next milestone

First Posted

Study publicly available on registry

August 20, 2019

Completed
5 days until next milestone

Study Start

First participant enrolled

August 25, 2019

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2022

Completed
11 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2023

Completed
Last Updated

November 29, 2023

Status Verified

November 1, 2023

Enrollment Period

2.9 years

First QC Date

August 17, 2019

Last Update Submit

November 25, 2023

Conditions

aGVHDStem Cell Transplant Complications

Keywords

aGVHD

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (9)

  • Six-month duration of response

    Six-month after treatment

  • Duration of response

    Day 90 after treatment

  • Nonrelapse mortality (NRM)

    2 years after treatment

  • Relapse rate

    2 years after treatment

  • Disease-free survival (DFS)

    2 years after treatment

  • +4 more secondary outcomes

Study Arms (2)

Ruxolitinib combined with Corticosteroids

EXPERIMENTAL

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.

Drug: RuxolitinibDrug: Corticosteroid

Corticosteroids

ACTIVE COMPARATOR

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

Drug: Corticosteroid

Interventions

RuxolitinibDRUG

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.

Also known as: New
Ruxolitinib combined with Corticosteroids
CorticosteroidDRUG

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.

Also known as: Traditional
CorticosteroidsRuxolitinib combined with Corticosteroids

Eligibility Criteria

Age14 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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\~IV aGVHD or intermediate or high risk aGVHD (based on ST2, REG3a, other experimental objects) within 100 days post-transplantation.

You may not qualify if:

  • 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:
  • 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.
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Chinese PLA General Hospital

Beijing, Beijing Municipality, 100853, China

Location

Related Publications (8)

  • 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.

    PMID: 21926960BACKGROUND

  • 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.

    PMID: 20827288BACKGROUND

  • 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.

    PMID: 26687425BACKGROUND

  • 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.

    PMID: 29545329BACKGROUND

  • 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: 30453910BACKGROUND

  • 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: 39438467DERIVED

  • 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.

    PMID: 35668528DERIVED

  • 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.

    PMID: 35123640DERIVED

MeSH Terms

Interventions

ruxolitinibAdrenal Cortex Hormones

Intervention Hierarchy (Ancestors)

HormonesHormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

  • Daihong Liu

    Chines PLA General Hospital

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Director

Study Record Dates

First Submitted

August 17, 2019

First Posted

August 20, 2019

Study Start

August 25, 2019

Primary Completion

August 1, 2022

Study Completion

June 30, 2023

Last Updated

November 29, 2023

Record last verified: 2023-11

Data Sharing

IPD Sharing
Will not share

Locations

CN(1)