Belumosudil With Ruxolitnib as Third Line Therapy for Chronic Graft Versus Host Disease (cGvHD)

NCT07643025 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: OZUHN-043 (BELRUX)
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

Brief 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. 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

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  Enrollment to 24 and 48 weeks after combination therapy.

Other Outcomes (1)

• Evaluate improvement in musculoskeletal involvement of sclerotic GvHD using the Photographic Range of Motion (P-ROM) score measurement

  After 4, 8, 12, 24, and 48 weeks of combination therapy.

Study Arms (1)

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.

Drug: Belumosudil; Drug: Ruxolitinib

Interventions

Belumosudil DRUG

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.

Combination therapy with two oral agents (belumosudil, ruxolitinib)

Ruxolitinib DRUG

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.

Combination therapy with two oral agents (belumosudil, ruxolitinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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)
• 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%.

Sponsors & Collaborators

• Dennis Kim: lead
• Sanofi: collaborator

Study Sites (1)

University Health Network

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Interventions

belumosudil; ruxolitinib

Central Study Contacts

Dennis Kim, MD

CONTACT

416-946-4501; dr.dennis.kim@uhn.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Medical Oncologist

Study Record Dates

• First Submitted: April 23, 2026
• First Posted: June 11, 2026
• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): November 1, 2029
• Study Completion (Estimated): November 1, 2030
• Last Updated: October 2, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)