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. For the first 28 days (Cycle 1), patients take ruxolitinib (10 mg twice daily). From Cycle 2, they add belumosudil (200 mg once or twice daily, depending on other medications) for 48 weeks (12 cycles) unless their condition worsens or side effects become intolerable. Follow-up visits occur 30 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.
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.
Lack of response or disease progression after prednisone ≥1 mg/kg/day for ≥1 week OR
Have never been treated with systemic steroids as first line therapy for cGvHD.
Receiving >0.5 mg/kg/day of prednisone or equivalent corticosteroids at the time of enrollment.
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.
Single group
Belumosudil
DrugPatients receive ruxolitinib (10 mg twice daily) alone for one 28-day cycle, then add belumosudil (200 mg once or twice daily if on a PPI) from cycles 2-12 (48 weeks total), unless cGvHD progresses or side effects become intolerable.
Ruxolitinib
DrugPatients receive ruxolitinib (10 mg twice daily) alone for one 28-day cycle, then add belumosudil (200 mg once or twice daily if on a PPI) from cycles 2-12 (48 weeks total), unless cGvHD progresses or side effects become intolerable.
Efficacy will be assessed using overall response rate (ORR) as per the NIH cGvHD Consensus Response Criteria at 24 weeks of combination treatment. Tolerability and safety will be assessed by the incidence and severity of adverse events (AEs)
The proportion of responders and its 95% confidence interval (using exact binomial methods) will be calculated.
Evaluate the response by assessing ORR at 48 weeks, Failure-free survival (FFS) at 24 & 48 weeks, and durable response rate in patients who achieve complete or partial response at 52 weeks. GvHD symptom burden is measured using modified Lee Symptom Scale
GvHD symptom burden improvement, measured serially measured by the modified Lee Symptom Scale, will be evaluated using repeated measure based on the general linear model. If p-value is less than 0.05, it demonstrates statistically significant change over time within subject.
Evaluate improvement in musculoskeletal involvement of sclerotic GvHD using the Photographic Range of Motion (P-ROM) score measurement
Partial response: Decrease in NIH Joint and Fascia Score by 1 or more points or increase in P-ROM score by 1 point for any site. Progression: Decrease in NIH Joint and Fascia Score by 1 or more points or increase in P-ROM score by 1 point for any site
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This trial is not recruiting at the moment. You can still explore other options:
