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aGVHDPhase 2NCT04061876

First Line Therapy for High Risk Acute GVHD

A Phase 2 study testing Ruxolitinib and Corticosteroid in people with aGVHD and Stem Cell Transplant Complications, run by Chinese PLA General Hospital at 1 site in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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 ) Read more about this study

Who is it for?
Ages 14 to 65 years
Conditions the study is for
aGVHD, Stem Cell Transplant Complications
What is being tested?
Ruxolitinib and Corticosteroid
Could I receive a placebo?
No, everyone receives an active treatment
How many people
198 participants
Where
1 siteChina
Study dates
25 Aug 2019to 30 Jun 2023
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 14 to 65 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 18Show fewer
  • 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.
  • Clinically significant respiratory disease that requires mechanical ventilation support or 50% oxygen.
  • Received Janus kinase inhibitor therapy after allo-HSCT for any indication.
  • 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.

Trial locations and contacts

1 site in 1 country.

China1 site

  • Chinese PLA General Hospital

    Beijing, Beijing Municipality, 100853

Other trials in China

About this study

Official title: Ruxolitinib in Combination With Corticosteroid as First Line Therapy for the Treatment of High Risk Acute Graft-Versus-Host Disease

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 )

Read the detailed description

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.

Being tested
Ruxolitinib, Corticosteroid
Keywords
aGVHD

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RuxolitinibDrug

    Also called New

    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.

  • CorticosteroidDrug

    Also called Traditional

    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.

Study groups in NCT04061876
Study groupRoleWhat they receive
Ruxolitinib combined with CorticosteroidsExperimentalParticipants 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.
Receives: Drug: Ruxolitinib; Drug: Corticosteroid
CorticosteroidsActive comparatorMethylprednisolone: 2mg/kg/d , iv or iv gtt for at least 1 week, then taper according to the clinical response.
Receives: Drug: Corticosteroid

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall response rate (ORR) at Day 28

    Defined as the proportion of participants demonstrating a complete response (CR), or partial response (PR).

    Measured: Day 28 after treatment

Secondary outcomes (9)

  1. 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.

    Measured: Six-month after treatment

  2. 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.

    Measured: Day 90 after treatment

  3. 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.

    Measured: 2 years after treatment

  4. Relapse rate

    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.

    Measured: 2 years after treatment

  5. Disease-free survival (DFS)

    Defined as the time from first dose of ruxolitinib 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. Survival will be calculated from the date of randomization.

    Measured: 2 years after treatment

  6. Overall survival (OS)

    Defined as the time from study enrollment (first day of ruxolitinib treatment) to death due to any cause. 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.

    Measured: 2 years after treatment

  7. GVHD-free and relapse-free survival (GRFS)

    GRFS was defined as the time onset of grade 3 to 4 aGVHD, moderate to severe cGVHD, or relapse/disease progression/death. GRFS 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.

    Measured: 2 years after treatment

  8. 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.

    Measured: 1 years after treatment

  9. Failure-free survival

    Failure-free survival (FFS) refers to the time from randomization to disease relapse or progression, non-relapse mortality, or the addition of new therapy for aGVHD.

    Measured: 2 years after treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Aug 2019
  2. Study start25 Aug 2019
  3. Primary completion1 Aug 2022
  4. Study completion30 Jun 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
198 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04061876
Sponsor's protocol ID
S2019-177-01
Status last verified
Nov 2023
First submitted
17 Aug 2019
Last updated
29 Nov 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 21926960

  • 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.

    PubMed 20827288

  • 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.

    PubMed 26687425

  • 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.

    PubMed 29545329

  • 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.

    PubMed 30453910

  • 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.

    PubMed 39438467

  • 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.

    PubMed 35668528

  • 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.

    PubMed 35123640

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ruxolitinib and Corticosteroid in people with aGVHD and Stem Cell Transplant Complications, run by Chinese PLA General Hospital at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall response rate (ORR) at Day 28 (time frame: Day 28 after treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04061876, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2023.

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