Belumosudil With Ruxolitnib as Third Line Therapy for Chronic Graft Versus Host Disease (cGvHD)
ConditioncGVHD
Trial statusNot yet recruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorDennis Kim
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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.
Strong CYP3A inducers
Trial design
Design model
Single group
Treatments tested in this trial
Belumosudil
DrugPatients 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.
Ruxolitinib
DrugPatients 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.
Treatment groups
53 Participants
are divided into 1 treatment groupGroup A: Combination therapy with two oral agents (belumosudil, ruxolitinib)Experimental treatment 2 interventions
Trial outcomes
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.
Time frame
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).
Time frame
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
Complete response: Both NIH Joint and Fascia Score 0 and P-ROM score 25 after previous involvement by at least one measure. 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: Increase in NIH Joint and Fascia Score by 1 or more points or decrease in P-ROM score by 1 point for any site.
Time frame
After 4, 8, 12, 24, and 48 weeks of combination therapy.Sponsors and contacts
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Source ClinicalTrials.gov
This trial is not recruiting at the moment. You can still explore other options: