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Hematopoietic Stem Cell Transplantation (HSCT)NCT07794514

Belumosudil Versus Ruxolitinib for Steroid-Refractory or Breakthrough Hepatic cGVHD

A study testing Ruxolitinib treatment, Belumosudil treatment and Belumosudil Switch to Ruxolitinib in people with Hematopoietic Stem Cell Transplantation (HSCT) and cGVHD, run by First Affiliated Hospital of Zhejiang University at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This prospective, randomized, open-label, multicenter trial aims to compare second-line treatment strategies for hepatic cGVHD after allo-HSCT. Ruxolitinib and belumosudil are both effective for cGVHD, but no head-to-head comparison specifically in hepatic cGVHD has been reported. Read more about this study

Who is it for?
Ages 12 years and older
What is being tested?
Ruxolitinib treatment, Belumosudil treatment and Belumosudil Switch to Ruxolitinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
170 participants
Where
1 siteChina
Study dates
1 Oct 2026to 31 Dec 2030
Phase
Interventional
Are there results?
Not yet: the study is under way

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 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Age ≥ 12 years at time of signing informed consent.
  • Received allogeneic hematopoietic stem cell transplantation.
  • Meets 2014 NIH consensus criteria for hepatic cGVHD (≥1 of: total bilirubin > 2×ULN, ALP > 2×ULN, ALT > 2×ULN, or liver biopsy-proven cGVHD-related injury), after excluding other causes.
  • ECOG performance status ≤ 2.
  • Able to take oral medication.
  • Life expectancy ≥ 6 months.
Show all 11Show fewer
  • Adequate organ function: ANC ≥ 1.0×10⁹/L, platelets ≥ 50×10⁹/L, creatinine clearance ≥ 30 mL/min.
  • Female patients of childbearing potential have negative pregnancy test and agree to effective contraception during study and for 6 months after last dose; male patients agree to same.
  • Willing and able to provide written informed consent and comply with study requirements.
  • Cohort 1 (Steroid-refractory): Progressive disease on stable steroids (1 mg/kg/day) within 1-2 weeks prior to screening, or persistent cGVHD without improvement after ≥4 weeks of prednisone (or equivalent) > 0.5 mg/kg/day. (Prior aGVHD JAK inhibitor use allowed if stopped ≥8 weeks.).
  • Cohort 2 (Breakthrough hepatic cGVHD): Patients on stable (≥2 weeks) ruxolitinib or belumosudil monotherapy for non-hepatic cGVHD for ≥4 weeks, who develop new-onset hepatic cGVHD or experience no response or progression on current therapy for hepatic cGVHD, not attributable to other etiologies (e.g., viral hepatitis, drug-induced liver injury, biliary obstruction, iron overload, alcoholic liver disease), with no prior exposure to the alternative study agent.

Who cannot join

  • Receiving newly initiated systemic cGVHD therapy other than corticosteroids and calcineurin inhibitors (CNIs); corticosteroids and CNIs must be on a stable regimen for ≥2 weeks prior to screening.
  • Uncontrolled active acute GVHD (≥ grade 2).
  • Active viral hepatitis or HIV infection.
  • Liver function abnormalities due to other causes, including but not limited to drug-induced liver injury, autoimmune hepatitis, alcoholic liver disease, biliary obstruction, VOD/SOS, iron overload, Gilbert's syndrome, or hemolysis.
  • Severe cardiovascular or cerebrovascular disease, including but not limited to: NYHA class ≥3, uncontrolled hypertension, severe arrhythmia, or myocardial infarction/stroke within 6 months.
  • Respiratory failure requiring mechanical ventilation, resting pulse oxygen saturation <90%, or severe/uncontrolled pulmonary cGVHD or other respiratory disease that may significantly affect patient safety or study assessment, per investigator judgment.
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  • Inability to take oral medication, severe gastrointestinal dysfunction (NCI CTCAE v5.0 ≥ grade 3), severe GI cGVHD requiring parenteral nutrition, daily diarrhea >1 L, or any other condition significantly affecting GI absorption.
  • Significant neurological or psychiatric history (including epilepsy or dementia) that makes the subject unsuitable for participation.
  • Relapsed primary malignancy or PTLD.
  • History of other malignancies, except cured and fully resected basal or squamous cell skin carcinoma, surgically cured cervical carcinoma in situ, resected ductal carcinoma in situ of the breast, prostate cancer (Gleason <6 with stable PSA >12 months), or other malignancies with no evidence of recurrence after curative treatment.
  • ECG abnormality: QTcF >450 ms (male) or >470 ms (female) at screening.
  • Known alcohol or drug dependence.
  • Pregnant or breastfeeding women.
  • Allergy to study drug or its excipients.
  • Any other condition that may affect patient safety or compliance, per investigator judgment.
  • Cohort 1: Prior cGVHD treatment with JAK inhibitors (e.g., ruxolitinib) or ROCK2 inhibitors (e.g., belumosudil); receipt of other investigational therapy within 30 days prior to randomization, or <5 half-lives since last investigational product.
  • Cohort 2: Patients with prior exposure to both ruxolitinib and belumosudil.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Fei Gao contact

+86 19857035073

gf0906@zju.edu.cn

China1 site, 1 recruiting

  • The First Affiliated Hospital of Zhejiang University School of Medicine

    Hangzhou, Zhejiang, 310006

    Yanmin Zhao, MD, 057187236706, yanminzhao@zju.edu.cn

    Recruiting

Other trials in China

About this study

Official title: Belumosudil Versus Ruxolitinib for Steroid-Refractory or Breakthrough Hepatic cGVHD: A Prospective, Multicenter Study With Randomization in Treatment-Naïve Patients and Switch in Pretreated Patients

This prospective, randomized, open-label, multicenter trial aims to compare second-line treatment strategies for hepatic cGVHD after allo-HSCT. Ruxolitinib and belumosudil are both effective for cGVHD, but no head-to-head comparison specifically in hepatic cGVHD has been reported. Two cohorts are enrolled: Cohort 1 comprises patients with steroid-refractory hepatic cGVHD without prior ruxolitinib or belumosudil exposure, randomized to receive either agent. Cohort 2 includes patients who develop new-onset hepatic cGVHD after ≥4 weeks of therapy with ruxolitinib or belumosudil for other-organ cGVHD (stable for ≥2 weeks), or patients with non-response/progression on either agent for hepatic cGVHD; these patients will be switched to the opposite drug. Key questions include: • In steroid-refractory hepatic cGVHD, does 24-week hepatic overall response rate differ between belumosudil and ruxolitinib? • What is the hepatic response rate after drug switching in Cohort 2? • How do the two agents compare in safety and tolerability for hepatic cGVHD? • What are their impacts on corticosteroid tapering, failure-free survival, and long-term outcomes? Participants will: • Receive assigned treatment per cohort and randomization • Undergo regular efficacy/safety monitoring, including hepatic cGVHD scoring, liver function tests, and adverse event recording • Provide peripheral blood samples at baseline and multiple on-treatment time points for exploratory biomarker analysis • Complete 24-week primary efficacy assessment with follow-up until progression or discontinuation Primary endpoint is 24-week hepatic overall response rate (CR+PR, per 2014 NIH cGVHD criteria). Secondary endpoints include duration of response, failure-free survival, corticosteroid tapering rate, safety (AE/SAE incidence), liver function improvement, and patient-reported outcomes. This head-to-head comparison will provide high-level evidence for selecting second-line and beyond therapies for hepatic cGVHD.

Being tested
Ruxolitinib treatment, Belumosudil treatment, Belumosudil Switch to Ruxolitinib, Ruxolitinib Switch to Belumosudil
Keywords
Hematopoietic Stem Cell Transplantation, Hepatic cGVHD, Belumosudil, Ruxolitinib

What participants receive

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

  • Ruxolitinib treatmentDrug

    Ruxolitinib treatment

  • Belumosudil treatmentDrug

    Belumosudil treatment

  • Belumosudil Switch to RuxolitinibDrug

    Belumosudil Switch to Ruxolitinib

  • Ruxolitinib Switch to BelumosudilDrug

    Ruxolitinib Switch to Belumosudil

Study groups in NCT07794514
Study groupRoleWhat they receive
Ruxolitinib GroupActive comparatorParticipants assigned to this arm will receive ruxolitinib administered orally at the standard approved dose and schedule for the treatment of steroid-refractory hepatic chronic graft-versus-host disease (cGVHD).
Receives: Drug: Ruxolitinib treatment
Belumosudil GroupExperimentalParticipants assigned to this arm will receive belumosudil administered orally at the standard approved dose and schedule for the treatment of steroid-refractory hepatic chronic graft-versus-host disease (cGVHD).
Receives: Drug: Belumosudil treatment
Belumosudil Switch to Ruxolitinib GroupOtherParticipants with breakthrough hepatic cGVHD on stable belumosudil therapy for non-hepatic cGVHD who develop new-onset hepatic cGVHD or have no response/progression on belumosudil, not attributable to other etiologies, and with no prior ruxolitinib exposure, will discontinue belumosudil and cross over to ruxolitinib.
Receives: Drug: Belumosudil Switch to Ruxolitinib
Ruxolitinib Switch to Belumosudil GroupOtherParticipants with breakthrough hepatic cGVHD on stable ruxolitinib therapy for non-hepatic cGVHD who develop new-onset hepatic cGVHD or have no response/progression on ruxolitinib, not attributable to other etiologies, and with no prior belumosudil exposure, will discontinue ruxolitinib and cross over to belumosudil.
Receives: Drug: Ruxolitinib Switch to Belumosudil

What is being measured

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

  1. Overall Response Rate (ORR) for Hepatic cGVHD at Week 24

    Measured: at Week 24 after treatment

Secondary outcomes (6)

  1. Best overall response (BOR)

    Measured: Assessed continuously throughout the study from the date of randomization，up to 24 weeks after treatment

  2. Duration of response (DOR)

    Measured: From first response to progression/death, whichever came first, assessed up to 2 years after the date of randomization

  3. Incidence of adverse events (AEs)

    Measured: Continuous monitoring from first dose to 30 days after last dose

  4. Quality of life (QoL) score

    Measured: Assessed at baseline, Week 12, Week 24, and end of treatment

  5. Overall survival (OS)

    Measured: From date of randomization until the date of death from any cause, whichever came first, assessed up to 2 years after the date of randomization.

  6. Failure-free survival (FFS)

    Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years after the date of randomization.

Timeline

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

  1. First posted31 Aug 2026
  2. Study start1 Oct 2026 (estimated)
  3. Primary completion1 Apr 2030 (estimated)
  4. Study completion31 Dec 2030 (estimated)

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 N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
170 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07794514
Sponsor's protocol ID
BR-HEP-CGVHD
Status last verified
Aug 2026
First submitted
25 Aug 2026
Last updated
31 Aug 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Jagasia MH, Greinix HT, Arora M, Williams KM, Wolff D, Cowen EW, Palmer J, Weisdorf D, Treister NS, Cheng GS, Kerr H, Stratton P, Duarte RF, McDonald GB, Inamoto Y, Vigorito A, Arai S, Datiles MB, Jacobsohn D, Heller T, Kitko CL, Mitchell SA, Martin PJ, Shulman H, Wu RS, Cutler CS, Vogelsang GB, Lee SJ, Pavletic SZ, Flowers ME. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant. 2015 Mar;21(3):389-401.e1. doi: 10.1016/j.bbmt.2014.12.001. Epub 2014 Dec 18.

    PubMed 25529383

  • Hall K, Lazaryan A, van der Laan M, Lee C, Logan AC, Gruber S, Kabadi S, Khan I, Nicholls C, Rota L, Nikai E, Ponomareva E, Koumas A, Waller EK. Efficacy and safety of belumosudil as compared with best available therapy for the treatment of cGVHD in the United States. Blood Adv. 2026 Feb 10;10(3):682-693. doi: 10.1182/bloodadvances.2025015832.

    PubMed 40875591

  • Lee SJ, Pavletic S, Blazar BR, Yao Y, Ji R, Marshall K, Cutler C; KD025-208 and ROCKstar Study Investigators. Belumosudil for Chronic Graft-Versus-Host Disease: Analysis of Long-Term Results from the KD025-208 and ROCKstar Studies. Transplant Cell Ther. 2025 Jul;31(7):434.e1-434.e10. doi: 10.1016/j.jtct.2025.04.020. Epub 2025 May 1.

    PubMed 40318736

  • Ibrahimova A, Bidgoli A, Ashraf A, Krogman A, Klink G, Teusink-Cross A, Schoettler ML, Davies SM, Khandelwal P. Real world experience using belumosudil for treatment of chronic graft versus host disease in children and young adults. Bone Marrow Transplant. 2026 Apr;61(4):487-489. doi: 10.1038/s41409-025-02795-9. Epub 2026 Jan 21. No abstract available.

    PubMed 41566004

  • Nalkurthi C, Schroder WA, Melino M, Irvine KM, Nyuydzefe M, Chen W, Liu J, Teng MWL, Hill GR, Bertolino P, Blazar BR, Miller GC, Clouston AD, Zanin-Zhorov A, MacDonald KPA. ROCK2 inhibition attenuates profibrogenic immune cell function to reverse thioacetamide-induced liver fibrosis. JHEP Rep. 2021 Oct 6;4(1):100386. doi: 10.1016/j.jhepr.2021.100386. eCollection 2022 Jan.

    PubMed 34917911

  • Modi B, Ngo D, Chen J, Yang D, Shan H, Sandhu K, Rashid N, Amanam I, Otoukesh S, Nakamura R, Ali H, Salhotra A. Belumosudil for the treatment of chronic graft-versus-host disease: a single center real-world experience. Bone Marrow Transplant. 2025 Apr;60(4):555-557. doi: 10.1038/s41409-024-02498-7. Epub 2025 Feb 4. No abstract available.

    PubMed 39905130

  • Michonneau D, Malard F, Le Grand S, Magro L, D'Aveni M, Tudesq JJ, Villate A, Meunier M, Maillard N, Castilla-Llorente C, Marcais A, Cabrera Q, Huynh A, Menard AL, Forcade E, Labussiere-Wallet H, Raus N, Loschi M. Efficacy and safety of belumosudil for treatment of cGVHD: multicenter retrospective analysis of the French cohort of the compassionate use program, on behalf of the French Society of Bone Marrow Transplantation and Cellular Therapy. Bone Marrow Transplant. 2025 Jun;60(6):779-786. doi: 10.1038/s41409-025-02554-w. Epub 2025 Apr 1.

    PubMed 40169928

  • Jagasia M, Lazaryan A, Bachier CR, Salhotra A, Weisdorf DJ, Zoghi B, Essell J, Green L, Schueller O, Patel J, Zanin-Zhorov A, Weiss JM, Yang Z, Eiznhamer D, Aggarwal SK, Blazar BR, Lee SJ. ROCK2 Inhibition With Belumosudil (KD025) for the Treatment of Chronic Graft-Versus-Host Disease. J Clin Oncol. 2021 Jun 10;39(17):1888-1898. doi: 10.1200/JCO.20.02754. Epub 2021 Apr 20.

    PubMed 33877856

  • Inamoto Y, Kato K, Kawakita T, Onishi Y, Matsuoka KI, Shiratori S, Ikegame K, Hiramoto N, Toyosaki M, Katayama Y, Murayama S, Sasagawa Y, Maeda Y, Hatake K, Teshima T. An open-label study of belumosudil, a selective ROCK2 inhibitor, as second or subsequent line of therapy for steroid-dependent/steroid-resistant chronic GVHD. Am J Hematol. 2024 Oct;99(10):1917-1926. doi: 10.1002/ajh.27424. Epub 2024 Jun 27.

    PubMed 38934629

  • Cutler C, Lee SJ, Arai S, Rotta M, Zoghi B, Lazaryan A, Ramakrishnan A, DeFilipp Z, Salhotra A, Chai-Ho W, Mehta R, Wang T, Arora M, Pusic I, Saad A, Shah NN, Abhyankar S, Bachier C, Galvin J, Im A, Langston A, Liesveld J, Juckett M, Logan A, Schachter L, Alavi A, Howard D, Waksal HW, Ryan J, Eiznhamer D, Aggarwal SK, Ieyoub J, Schueller O, Green L, Yang Z, Krenz H, Jagasia M, Blazar BR, Pavletic S. Belumosudil for chronic graft-versus-host disease after 2 or more prior lines of therapy: the ROCKstar Study. Blood. 2021 Dec 2;138(22):2278-2289. doi: 10.1182/blood.2021012021.

    PubMed 34265047

  • Zeiser R, Russo D, Ram R, Hashmi SK, Chakraverty R, Middeke JM, Musso M, Giebel S, Uzay A, Langmuir P, Hamad N, Burock K, Gowda M, Stefanelli T, Lee SJ, Teshima T, Locatelli F. Ruxolitinib in Patients With Corticosteroid-Refractory or Corticosteroid-Dependent Chronic Graft-Versus-Host Disease: 3-Year Final Analysis of the Phase III REACH3 Study. J Clin Oncol. 2025 Aug 10;43(23):2566-2571. doi: 10.1200/JCO-24-02477. Epub 2025 Jun 25.

    PubMed 40561385

  • Zeiser R, Polverelli N, Ram R, Hashmi SK, Chakraverty R, Middeke JM, Musso M, Giebel S, Uzay A, Langmuir P, Hollaender N, Gowda M, Stefanelli T, Lee SJ, Teshima T, Locatelli F; REACH3 Investigators. Ruxolitinib for Glucocorticoid-Refractory Chronic Graft-versus-Host Disease. N Engl J Med. 2021 Jul 15;385(3):228-238. doi: 10.1056/NEJMoa2033122.

    PubMed 34260836

  • Zeiser R, Lee SJ. Three US Food and Drug Administration-approved therapies for chronic GVHD. Blood. 2022 Mar 17;139(11):1642-1645. doi: 10.1182/blood.2021014448.

    PubMed 35081254

  • Hematopoietic Stem Cell Application Group, Chinese Society of Hematology, Chinese Medical Association. [Chinese expert consensus on the diagnosis and treatment of chronic graft-versus-host disease (2024)]. Zhonghua Xue Ye Xue Za Zhi. 2024 Aug 14;45(8):713-726. doi: 10.3760/cma.j.cn121090-20240611-00217. Chinese.

    PubMed 39307718

Questions about this trial

What is this clinical trial studying?

A study testing Ruxolitinib treatment, Belumosudil treatment and Belumosudil Switch to Ruxolitinib in people with Hematopoietic Stem Cell Transplantation (HSCT) and cGVHD, run by First Affiliated Hospital of Zhejiang University 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 11 inclusion and 17 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: looking for participants now, as of the sponsor's last update on 31 Aug 2026. 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.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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

Contact Fei Gao (+86 19857035073, gf0906@zju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rate (ORR) for Hepatic cGVHD at Week 24 (time frame: at Week 24 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 NCT07794514, which also lists 14 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 31 Aug 2026.

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