A Phase 2, Open-label, Multicenter Study to Evaluate the Safety and Efficacy of Belumosudil in Black or African American, American Indian or Alaska Native, and Native Hawaiian or Other Pacific Islander Participants With Chronic Graft Versus Host Disease (cGVHD) After At Least 2 Prior Lines of Systemic Therapy
Trial Snapshot
- Phase
- Phase 2
- Status
- Withdrawn
- Sponsor
- Enrollment
- 36
- Locations
- 3
- Primary Endpoint
- Change from baseline in corrected QT interval using Fridericia's formula (QTc[F])
Study Overview
Brief Summary
The purpose of this study is to measure safety and efficacy of oral belumosudil in Black or African American, American Indian or Alaska Native, and Native Hawaiian or Other Pacific Islander male and female participants with cGVHD who have previously been treated with at least 2 prior lines of systemic therapy aged 12 years and above.
The duration of participants participation will be up to 4 weeks for screening, treatment until clinically significant progression of disease, and 4 weeks of safety follow-up, and then long-term follow-up every 12 weeks.1 Cycle = 28 days.
Detailed Description
Up to 4 weeks for screening, treatment until clinically significant progression of disease, 4 weeks of safety follow-up and then long-term follow-up every 12 weeks.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 12 Years to — (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Participants are included in the study if any of the following criteria apply:
- •Participant is Black or African American, or American Indian or Alaska Native, or Native Hawaiian or Other Pacific Islander by self-identification.
- •Previously received at least 2 and not more than 5 lines of systemic therapy for cGVHD.
- •Receiving glucocorticoid therapy with a stable dose over the 2 weeks prior to screening.
- •Have persistent cGVHD manifestations and systemic therapy is indicated.
- •Karnofsky (if aged ≥ 16 years) / Lansky (if aged < 16 years) Performance Score of ≥
- •At least 12 years of age; weight ≥ 40 kilograms (kg).
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x upper limit of normal (ULN).
- •Total bilirubin ≤ 1.5 x ULN.
- •Contraception (with double contraception methods) for male and female participants; not pregnant or breastfeeding for female participants
- •Capable of giving signed informed consent.
Exclusion Criteria
- •Participants are excluded from the study if any of the following criteria apply:
- •Participant has not been on a stable dose/regimen of systemic cGVHD treatment(s) for at least 2 weeks prior to screening. (Note: Concomitant corticosteroids, calcineurin inhibitors, sirolimus, MMF, methotrexate, rituximab, and ECP are acceptable. Systemic investigational GVHD treatments are not permitted).
- •Histological relapse of the underlying cancer or post-transplant lymphoproliferative disease at the time of screening.
- •Current treatment with ibrutinib or ruxolitinib. Prior treatment with ibrutinib or ruxolitinib is allowed with a washout of at least 28 days prior to enrollment.
- •History or other evidence of severe illness or any other conditions that would make the participant, in the opinion of the Investigator, unsuitable for the study (such as malabsorption syndromes, poorly controlled psychiatric disease, or coronary artery disease).
- •Corrected QT interval using Fridericia's formula (QTc[F]) > 480 ms.
- •Forced expiratory volume (in the first second; FEV1) ≤ 39% The above information is not intended to contain all considerations relevant to the potential participation in a clinical trial.
Arms & Interventions
Belumosudil
Participants will receive belumosudil orally, once daily (QD) or twice daily (BID) if they are taking strong CYP3A4 inducers or proton pump inhibitors.
Intervention: Belumosudil (Drug)
Outcomes
Primary Outcomes
Change from baseline in corrected QT interval using Fridericia's formula (QTc[F])
Time Frame: Baseline; up to approximately 12 months
Number of participants with treatment emergent adverse events and serious adverse events
Time Frame: Up to approximately 48 months
Safety will be assessed by monitoring adverse events, physical Examinations, clinical laboratory evaluations, vital sign measurements, and ECG parameters.
Number of participants with clinically significant laboratory abnormalities
Time Frame: Up to approximately 12 months
Change from baseline in systolic and diastolic blood pressure
Time Frame: Baseline; up to approximately 12 months
Change from baseline in heart rate
Time Frame: Baseline; up to approximately 12 months
Overall Response Rate (ORR)
Time Frame: Up to approximately 12 months
The ORR is defined as the proportion of participants meeting the overall response criteria assessment of Complete Response (CR) or Partial Response (PR) as defined by the 2014 NIH Consensus Development Project on Clinical Trials in cGVHD at any post-baseline response assessment.
Secondary Outcomes
- Duration of Response (DOR)(Up to approximately 12 months)
- Change from baseline in the Lee Symptom Scale Score: Number of participants with a ≥ 7-point reduction on 2 consecutive assessments(Baseline; up to approximately 12 months)
- Time to Response (TTR)(Up to approximately 12 months)
- Time to Next Treatment (TTNT)(Up to approximately 12 months)
- Change from baseline in corticosteroid dose(Baseline; up to approximately 12 months)
- Change from baseline in the Lee Symptom Scale Score: Number of participants with a ≥ 7-point reduction(Baseline; up to approximately 12 months)
- Response rate by organ system(Up to approximately 12 months)
- Change from baseline in calcineurin inhibitor dose(Baseline; up to approximately 12 months)
- Overall survival (OS)(Up to approximately 12 months)
- Plasma belumosudil concentrations(Day 1 of Cycles 2, 3, 5, and 7 (1 Cycle = 28 days))
- Change from baseline in the Lee Symptom Scale Score: Duration of a ≥ 7 point reduction(Baseline; up to approximately 12 months)
- Number of participants who have a best response of PR and CR(Up to approximately 12 months)
- Change from baseline in cGVHD global severity rating using the Clinician-Reported Global cGVHD Activity Assessment(Baseline; up to approximately 12 months)
- Failure-free survival (FFS)(Up to approximately 12 months)
- Change from baseline in symptom activity as based on cGVHD Activity Assessment Patient Self-Report(Baseline; up to approximately 12 months)