cGVHDPhase 2BELRUXNCT07643025
Belumosudil With Ruxolitnib as Third Line Therapy for Chronic Graft Versus Host Disease (cGvHD)
A Phase 2 study testing Belumosudil and Ruxolitinib in people with cGVHD, run by Dennis Kim at 1 site in Canada.
Trial summary
Chronic graft-versus-host disease (cGvHD) is a serious condition that can happen after a stem cell or bone marrow transplant. The donor's immune cells attack the patient's body, causing inflammation, pain, and damage to organs like the skin, liver, or lungs. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- cGVHD
- What is being tested?
- Belumosudil and Ruxolitinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 53 participants
- Where
- 1 siteCanada
- Study dates
- Nov 2026to Nov 2030
- Phase
- Phase 2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18 years of age or older at the time of enrollment.
- Has previously been diagnosed with moderate to severe cGvHD OR mild cGvHD with high-risk features (defined as platelet counts < 100 x 109/L at screening).
- Capable of providing informed consent.
- Meets the criteria of steroid-refractory cGvHD after first line corticosteroids therapy at the time of enrollment, as follows:
- Lack of response or disease progression after prednisone ≥1 mg/kg/day for ≥1 week OR
- Disease persistence without improvement with prednisone >0.5 mg/kg/day or 1 mg/kg/every other day for ≥4 weeks OR
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- Increase in prednisone dose to >0.25 mg/kg/day after 2 unsuccessful attempts to taper the dose.
- Taking a steroid dose at the time of enrollment that is <0.5mg/kg/day of prednisone or equivalent.
- Absolute neutrophil count ≥ 1.5 × 109/L within 2 weeks (14 days) of enrollment.
- Platelet count ≥ 50 × 109/L within 2 weeks of enrollment.
- ALT and AST ≤ 5 × ULN (<7.5 x ULN if due to liver GvHD) within 2 weeks of enrollment.
- Total bilirubin ≤ 1.5 × ULN within 2 weeks of enrollment.
- Glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m2 using the MDRD-4 variable formula within 2 weeks of enrollment.
- Female patients of childbearing potential will use 2 reliable methods of birth control (refer to Section 9.3) or be surgically sterile, or abstain from heterosexual activity for the course of the study from the time of study enrollment until 3 months following the discontinuation of all study treatment and agree not to donate or cryopreserve eggs (ova, oocytes) for the purpose of reproduction during this period. Patients of childbearing potential are those who have not been surgically sterilized (i.e. have a documented hysterectomy, or documented bilateral salpingectomy, or documented bilateral oophorectomy) or have not been free from menses for > 2 years. For individuals with permanent infertility due to an alternate medical cause other than the above (e.g. Mullerian agenesis, androgen insensitivity, gonadal dysgenesis) investigator discretion should be applied to determining study entry eligibility.
- Male patients will use an adequate method of contraception for the course of the study from the time of enrollment to 3 months after discontinuation of all study treatment. These participants must refrain from donating or cryopreserving sperm, be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent or must agree to use contraception (a male condom and an additional highly effective contraceptive method as described in Section 9.3) when having sexual intercourse with a woman of childbearing potential who is not currently pregnant.
- Patients showing overlap syndrome with components of acute GvHD (aGvHD) at the time of enrollment are eligible to participate unless the acute component of their overlap syndrome is Grade 3 or 4.
- Must be able and willing to comply with study procedures.
Who cannot join
- Receiving ruxolitinib for active steroid refractory acute GvHD at the time of enrollment. Participants with a prior history of aGvHD are eligible only if the aGvHD has achieved CR or PR prior to screening and the participants subsequently developed steroid refractory cGvHD.
- Have never been treated with systemic steroids as therapy for cGvHD.
- Receiving >0.5 mg/kg/day of prednisone or equivalent corticosteroids at the time of enrollment.
- Ongoing use of any of the following pharmaceutical agents, which cannot be discontinued prior to belumosudil treatment (PRN/as-needed use is permissible if it can be fully discontinued at least 7 days prior to enrollment and is not expected to resume during the study):
- Strong CYP3A inducers
- UGT1A1 substrates (e.g., raltegravir)
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- P-gp substrates (e.g., dabigatran)
- OATP1B1/OATP1B3/BCRP substrates (e.g., rosuvastatin)
- Has had prior treatment with a JAK inhibitor or ROCK2 inhibitor within 8 weeks of enrollment. Participants who received a JAK inhibitor for aGvHD are eligible only if they achieved CR or PR prior to screening.
- Active uncontrolled bacterial, fungal, parasitic, or viral infection. Infections are considered controlled if appropriate therapy has been initiated and, at the time of screening, no signs of infection are present.
- Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection that requires treatment, or is at risk for HBV reactivation (i.e., positive HBsAg) within 4 weeks of enrollment. Participants with negative HBsAg and positive total HBc antibody may be included if HBV DNA is undetectable at the time of screening. Participants who are positive for HCV antibody are eligible only if PCR is negative for HCV RNA. Participants whose immune status is unknown or uncertain must have results confirming immune status before enrollment.
- Known active infection or history of human immunodeficiency virus (HIV).
- Evidence of relapsed primary hematologic disease, or receipt of treatment for relapse after the allo-HCT was performed. Patients treated with Donor Lymphocyte Infusion (DLI) who have developed GvHD will not be excluded if the primary hematological disease has resolved.
- Maintenance therapy for the primary hematologic disease started within 4 weeks before initiation of study treatment (Cycle 1 Day 1) or plans to start maintenance therapy after Day 1.
- Participants on mechanical ventilation, requiring oxygen support or with a FEV1 < 30%.
- History or current diagnosis of cardiac disease indicating significant risk of safety for participation in the study, such as uncontrolled or significant cardiac disease, including any of the following:
- Recent myocardial infarction (within 6 months of enrollment)
- New York Heart Association Class III or IV congestive heart failure
- Unstable angina (within 6 months of enrollment)
- Clinically significant (symptomatic) cardiac arrhythmias (e.g. sustained ventricular tachycardia, and clinically significant second or third degree AV block without a pacemaker).
- Uncontrolled hypertension, defined as blood pressure that remains above 130/80 mmHg in spite of concurrent use of at least three antihypertensive agents of different classes.
- Patients with known active CNS disease (malignant involvement of CNS).
- Patients with active acute GvHD grade III-IV.
- History or other evidence of severe illness or any other conditions that would make the patient, in the opinion of the treating Investigator, unsuitable for the study (such as malabsorption syndromes, poorly controlled psychiatric disease or coronary artery disease).
- Known hypersensitivity to belumosudil, ruxolitinib or any of their excipients
- Patients unable to swallow oral medications
- Female participants who are pregnant or breastfeeding
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Phase 2, Single Arm, Belumosudil and Ruxolitinib Combination 3rd Line Therapy After 2nd Line Ruxolitinib Failure for Chronic Graft vs Host Disease (cGvHD) Treatment (BELRUX)
Chronic graft-versus-host disease (cGvHD) is a serious condition that can happen after a stem cell or bone marrow transplant. The donor's immune cells attack the patient's body, causing inflammation, pain, and damage to organs like the skin, liver, or lungs. For patients with moderate to severe cGvHD who don't improve with or can't tolerate standard front line therapy with steroids, there's a significant unmet need. Steroid-refractory cGvHD is hard to treat, with limited effective options, often leading to ongoing symptoms and reduced quality of life.
This Phase II study tests a new treatment combining two oral drugs, ruxolitinib and belumosudil, for these patients. Both drugs have helped cGvHD individually, but this trial explores if they work better together. Patients will begin on ruxolitinib (10 mg twice daily) and will continue for up to 48 weeks. Upon ruxolitinib treatment failure, patients will add belumosudil (200 mg once or twice daily, depending on other medications) in addition to ruxolitinib for 48 weeks (12 cycles) unless their condition worsens or side effects become intolerable. Follow-up visits occur 28 days and 6 months after treatment ends to check health status.
The study is non-randomized (all get the same treatment) and open-label (patients and doctors know the drugs used). It aims to see if this combination better controls cGvHD in patients where steroids failed. This could offer hope for better symptom management and improved quality of life for those with limited treatment options.
- Conditions
- cGVHD
- Being tested
- Belumosudil, Ruxolitinib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BelumosudilDrug
Patients receive ruxolitinib (10 mg twice daily) alone for one 28-day cycle for up to 48 weeks. Upon documentation of ruxolitinib failure, patients will begin taking belumosudil in addition to ruxolitinib, at a dose of 200 mg OD or 200 mg BID (if on a PPI) for 48 weeks total (i.e. 12 cycles), unless cGvHD progresses or side effects become intolerable.
RuxolitinibDrug
Patients receive ruxolitinib (10 mg twice daily) alone for one 28-day cycle for up to 48 weeks. Upon documentation of ruxolitinib failure, patients will begin taking belumosudil in addition to ruxolitinib, at a dose of 200 mg OD or 200 mg BID (if on a PPI) for 48 weeks total (i.e. 12 cycles), unless cGvHD progresses or side effects become intolerable.
| Study group | Role | What they receive |
|---|---|---|
| Combination therapy with two oral agents (belumosudil, ruxolitinib) | Experimental | Ruxolitinib monotherapy as second line treatment for up to 48 weeks. Upon documented ruxolitinib failure, patients transition to belumosudil and ruxolitinib combination 3rd line therapy for 48 weeks (i.e. 12 cycles), until progression of cGVHD, or intolerance to either agent, whichever occurs sooner. Patients will be monitored for documented individual efficacy/safety/toxicity as third line treatment in cGvHD patients. Receives: Drug: Belumosudil; Drug: Ruxolitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy will be assessed using failure-free survival (FFS) at 48 weeks in the belumosudil + ruxolitinib 3rd-line phase (i.e. after initiation of the combination following documented ruxolitinib 2nd-line failure for chronic GvHD).
The proportion of responders and its 95% confidence interval (estimated by the Kaplan-Meier method) will be calculated.
Measured: Enrollment to 24 and 48 weeks after combination therapy.
Secondary outcomes (1)
Response will be assessed using Overall Response Rate (ORR) and FFS at 24 & 48 weeks, and durable response rate in patients who achieve complete or partial response at 48 weeks. GvHD symptom burden is measured using modified Lee Symptom Scale.
Analyses:
- Safety/Tolerability: Incidence and severity of AEs summarized by frequency, percentage, grade (CTCAE v5.0), and relationship to study drug.
- ORR at 48 weeks, FFS, Durable response: Kaplan-Meier estimates with 95% CI.
- Ruxolitinib failure: cumulative incidence of ruxolitinib failure and cause of failure at 24 and 48 weeks; failure rate and ORR for ruxolitinib 2nd line therapy summarized descriptively with 95% CI.
- GvHD Symptom burden: Repeated measures analysis using general linear model (p<0.05 for significance).
Measured: Enrollment to 24 and 48 weeks after combination therapy.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2026
- Study startNov 2026 (estimated)
- Primary completionNov 2029 (estimated)
- Study completionNov 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for cGVHDStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 53 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Dennis Kim
- Sponsor type
- University, hospital or other
- Collaborators
- Sanofi
- Responsible party
- Sponsor-investigator, Dennis Kim, University Health Network, Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07643025
- Sponsor's protocol ID
- OZUHN-043 (BELRUX)
- Acronym
- BELRUX
- Status last verified
- Sep 2026
- First submitted
- 23 Apr 2026
- Last updated
- 2 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2, Single Arm, Belumosudil and Ruxolitinib Combination 3rd Line Therapy After 2nd Line Ruxolitinib Failure for Chronic Graft vs Host Disease (cGvHD) Treatment (BELRUX)
- ClinicalTrials.gov ID
- NCT07643025
- Acronym / sponsor ID
- BELRUX / OZUHN-043 (BELRUX)
- Conditions
- cGVHD
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 53 participants (estimated)
- Lead sponsor
- Dennis KimUniversity, hospital or other
- Collaborators
- Sanofi
- Study start
- Nov 2026 (estimated)
- Primary completion
- Nov 2029 (estimated)
- Study completion
- Nov 2030 (estimated)
- First posted
- 11 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Chronic graft-versus-host disease (cGvHD) is a serious condition that can happen after a stem cell or bone marrow transplant. The donor's immune cells attack the patient's body, causing inflammation, pain, and damage to organs like the skin, liver, or lungs. For patients with moderate to severe cGvHD who don't improve with or can't tolerate standard front line therapy with steroids, there's a significant unmet need. Steroid-refractory cGvHD is hard to treat, with limited effective options, often leading to ongoing symptoms and reduced quality of life.
This Phase II study tests a new treatment combining two oral drugs, ruxolitinib and belumosudil, for these patients. Both drugs have helped cGvHD individually, but this trial explores if they work better together. Patients will begin on ruxolitinib (10 mg twice daily) and will continue for up to 48 weeks. Upon ruxolitinib treatment failure, patients will add belumosudil (200 mg once or twice daily, depending on other medications) in addition to ruxolitinib for 48 weeks (12 cycles) unless their condition worsens or side effects become intolerable. Follow-up visits occur 28 days and 6 months after treatment ends to check health status.
The study is non-randomized (all get the same treatment) and open-label (patients and doctors know the drugs used). It aims to see if this combination better controls cGvHD in patients where steroids failed. This could offer hope for better symptom management and improved quality of life for those with limited treatment options.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Combination therapy with two oral agents (belumosudil, ruxolitinib) | Experimental | Drug: Belumosudil, Drug: RuxolitinibRuxolitinib monotherapy as second line treatment for up to 48 weeks. Upon documented ruxolitinib failure, patients transition to belumosudil and ruxolitinib combination 3rd line therapy for 48 weeks (i.e. 12 cycles), until progression of cGVHD, or intolerance to either agent, whichever occurs sooner. Patients will be monitored for documented individual efficacy/safety/toxicity as third line treatment in cGvHD patients. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 18 years of age or older at the time of enrollment.
- Has previously been diagnosed with moderate to severe cGvHD OR mild cGvHD with high-risk features (defined as platelet counts < 100 x 109/L at screening).
- Capable of providing informed consent.
- Meets the criteria of steroid-refractory cGvHD after first line corticosteroids therapy at the time of enrollment, as follows:
- Taking a steroid dose at the time of enrollment that is <0.5mg/kg/day of prednisone or equivalent.
Key exclusion criteria (27 listed)
- Receiving ruxolitinib for active steroid refractory acute GvHD at the time of enrollment. Participants with a prior history of aGvHD are eligible only if the aGvHD has achieved CR or PR prior to screening and the participants subsequently developed steroid refractory cGvHD.
- Have never been treated with systemic steroids as therapy for cGvHD.
- Receiving >0.5 mg/kg/day of prednisone or equivalent corticosteroids at the time of enrollment.
- Ongoing use of any of the following pharmaceutical agents, which cannot be discontinued prior to belumosudil treatment (PRN/as-needed use is permissible if it can be fully discontinued at least 7 days prior to enrollment and is not expected to resume during the study):
- Has had prior treatment with a JAK inhibitor or ROCK2 inhibitor within 8 weeks of enrollment. Participants who received a JAK inhibitor for aGvHD are eligible only if they achieved CR or PR prior to screening.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BelumosudilPatients receive ruxolitinib (10 mg twice daily) alone for one 28-day cycle for up to 48 weeks. Upon documentation of ruxolitinib failure, patients will begin taking belumosudil in addition to ruxolitinib, at a dose of 200 mg OD or 200 mg BID (if on a PPI) for 48 weeks total (i.e. 12 cycles), unless cGvHD progresses or side effects become intolerable. | Drug | Combination therapy with two oral agents (belumosudil, ruxolitinib) |
| RuxolitinibPatients receive ruxolitinib (10 mg twice daily) alone for one 28-day cycle for up to 48 weeks. Upon documentation of ruxolitinib failure, patients will begin taking belumosudil in addition to ruxolitinib, at a dose of 200 mg OD or 200 mg BID (if on a PPI) for 48 weeks total (i.e. 12 cycles), unless cGvHD progresses or side effects become intolerable. | Drug | Combination therapy with two oral agents (belumosudil, ruxolitinib) |
Primary outcome
Efficacy will be assessed using failure-free survival (FFS) at 48 weeks in the belumosudil + ruxolitinib 3rd-line phase (i.e. after initiation of the combination following documented ruxolitinib 2nd-line failure for chronic GvHD).
Time frame: Enrollment to 24 and 48 weeks after combination therapy.
The proportion of responders and its 95% confidence interval (estimated by the Kaplan-Meier method) will be calculated.
1 secondary outcome
Response will be assessed using Overall Response Rate (ORR) and FFS at 24 & 48 weeks, and durable response rate in patients who achieve complete or partial response at 48 weeks. GvHD symptom burden is measured using modified Lee Symptom Scale.
Time frame: Enrollment to 24 and 48 weeks after combination therapy.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Belumosudil and Ruxolitinib in people with cGVHD, run by Dennis Kim at 1 site in Canada.
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 17 inclusion and 27 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: opening soon, as of the sponsor's last update on 2 Oct 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 Canada. 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?
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 Dennis Kim, MD (416-946-4501 ext. x2464, dr.dennis.kim@uhn.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy will be assessed using failure-free survival (FFS) at 48 weeks in the belumosudil + ruxolitinib 3rd-line phase (i.e. after initiation of the combination following documented ruxolitinib 2nd-line failure for chronic GvHD). (time frame: Enrollment to 24 and 48 weeks after combination therapy.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Oct 2026.