Phase 1/2 Multicenter Study of Belumosudil Mesilate in Pediatric Patients with Moderate-to-Severe Chronic Graft Versus Host Disease
- Trial ID
- 2024-511508-18-00
- Protocol
- DFI17893
Trial statistics
Diseases & Conditions
Objectives
The primary objectives of this study are to establish the Recommended Pediatric Equivalent Dose (RPED) during Phase 1 and to evaluate the overall response rate (ORR) by Week 25 or Cycle 7 Day 1, whichever occurs first, during Phase 2 in pediatric patients with chronic graft versus host disease. 5, 9. The secondary objectives include:
- Evaluation of safety (4).
- Assessment of pharmacokinetics (6).
- Determination of duration of response (DOR).
- Analysis of response by organ.
- Evaluation of failure-free survival (FFS).
- Measurement of overall survival (OS).
- Assessment of time to response (TTR).
- Evaluation of overall response rate (ORR) at 24 weeks during Phase 1.
Participants
This clinical trial involves 27 participants diagnosed with chronic graft versus host disease. The study population consists of male and female pediatric patients. For Phase 1, the age range is 1 to <12 years, while Phase 2 includes participants aged 1 to <18 years. Eligible individuals must have undergone an allogeneic hematopoietic cell transplantation and possess a life expectancy exceeding 6 months. The study population must exhibit active moderate to severe disease that is refractory to or has recurred after 2 to 5 prior lines of systemic therapy. Additional requirements include a body weight of at least 8 kg and a Lansky-Play or Karnofsky performance scale score of ≥60. If corticosteroid therapy is utilized, dosage must remain stable for at least 2 weeks prior to the administration of the investigational medicinal product. The primary objectives are:
- Establish the Recommended Pediatric Equivalent Dose
- Evaluate the overall response rate by Week 25 or Cycle 7 Day 1
Plans and Procedures
This open-label, Phase 1/2, multicenter study evaluates the efficacy and safety of belumosudil in pediatric patients aged 1 to <18 years with active moderate-to-severe chronic graft versus host disease. The first phase aims to establish the Recommended Pediatric Equivalent Dose (RPED) by measuring the area under the curve (AUC). The second phase evaluates the overall response rate (ORR) at Week 25 or Cycle 7 Day 1, whichever occurs first. Participants must have undergone an allogeneic hematopoietic cell transplant and demonstrated disease that is refractory to or has recurred after two to five lines of systemic therapy. Administration of the investigational medicinal product occurs via oral route or through a nasogastric tube. Secondary endpoints include the assessment of treatment-emergent adverse events (TEAEs), duration of response (DOR), failure-free survival (FFS), and overall survival (OS).
Treatment
The experimental treatment consists of belumosudil mesilate, an orphan drug. This substance is administered in two pharmaceutical forms: film-coated tablets and oral suspension. The administration route for the tablets is oral, while the suspension may be administered via the oral route, nasogastric tube, or percutaneous endoscopic gastrostomy tube.
Efficacy
Efficacy assessment in this study of chronic graft versus host disease is divided into two phases. In Phase 1, efficacy and pharmacokinetic parameters include area under the curve (AUC), Cmax, AUC0-6h, overall response rate (ORR), duration of response (DOR), response by organ, failure-free survival (FFS), overall survival (OS), and time to response (TTR).
In Phase 2, the primary efficacy endpoint is the proportion of participants achieving an overall response, defined as partial response (PR) or complete response (CR), by Week 25 or Cycle 7 Day 1, whichever occurs first. Secondary efficacy parameters for Phase 2 include Ctrough of belumosudil, DOR, response by organ, FFS, OS, and TTR.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Participant must be 1 to <18 years of age, at the time the consent/assent is signed. For Phase 1: participant must be 1 to <12 years of age, at the time the consent/assent is signed. For Phase 2: participant must be 1 to <18 years of age, at the time the consent/assent is signed.
- Life expectancy of >6 months
- Participants can take the IMP orally or via a nasogastric tube
- Participant has undergone an allogeneic HCT
- Has active moderate to severe cGVHD, defined using the NIH Consensus diagnosis and staging criteria for which systemic therapy is required
- cGVHD is refractory to or has recurred after at least 2 prior lines of systemic treatment
- Has received at least two lines of prior systemic therapy for cGVHD, but no more than 5 lines.
- If participant receives corticosteroid therapy for cGVHD, the dose must be stable for at least 2 weeks prior to the first dose of the IMP
- Has a Lansky-Play (if aged <16 years) or Karnofsky (if aged ≥16 years) performance scale of ≥60
- Body weight of 8 kg and above
- Contraceptive use by sexually active male and female should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
- The participant or their legally authorized representative (LAR) must be capable of giving signed informed consent
Exclusion Criteria
- Progressive underlying disease or post-transplant lymphoproliferative disease within 4 weeks prior to the first dose of the IMP.
- Treatment with any non-GVHD investigational agent, or any investigational device or procedure, within 28 days (or 5 half-lives, whichever is longer) of enrollment, prior to the first dose of the IMP
- For Phase 1 only: Administration with strong CYP3A4 inducers is not allowed within 14 days or 5 half-lives (whichever is longer) of the first dose of IMP until the study intervention discontinuation.
- For Phase 1 only: PPIs are not allowed within 1 day or 5 half-lives (whichever is longer) of the first dose of IMP and Day 15 of Cycle 1. They can be restarted on Cycle 1 Day 16.
- Absolute neutrophil count <1.0 × 109/L. The use of granulocyte-colony stimulating factor (G-CSF) is not allowed within 7 days prior to the ANC test to reach this level during screening
- Platelet count <25× 109/L. Platelet transfusions are not allowed within 72 hours before hematology screening test. Participants with platelet transfusion refractoriness will be excluded. (Participants who have suboptimal responses to at least 2 transfusions will be considered as platelet transfusion refractory)
- Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >3× upper limit of normal (ULN) (> 5x ULN if abnormalities are due to cGVHD)
- Total bilirubin >1.5 × ULN (>3 x ULN if Gilbert’s syndrome or if abnormalities are due to cGVHD)
- Glomerular filtration rate (GFR) <30 mL/min/1.73 m2 using the revised Bedside Schwartz calculator
- Participants with an active viral disease including hepatitis B virus (HBV) and hepatitis C virus (HCV)
- Active uncontrolled Cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection
- Diagnosed with another malignancy (other than malignancy for which transplant was performed) within 3 years prior to the first dose of the IMP
- Known history of human immunodeficiency virus (HIV)
- Not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures
- 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, active, uncontrolled infections, or poorly controlled psychiatric disease)
- Has a forced expiratory volume (in the first second; FEV1) ≤39% or has lung score of 3
- Female participants who are pregnant or breastfeeding
- The use of herbal and recreational drugs within 7 days before the start of study intervention
- Participant has had previous exposure to belumosudil
- Administration of live or live-attenuated vaccines is prohibited within 28 days or 5 elimination half-lives of the respective vaccine, whichever is longer, prior to IMP administration and until study intervention discontinuation
- Participants who meet any of the following criteria regarding systemic GVHD treatments: - Participants who newly initiated any systemic GVHD treatment within 14 days prior to the first dose of belumosudil.
- Participants who meet any of the following criteria regarding systemic GVHD treatments: - Participants receiving systemic GVHD treatments ibrutinib, ruxolitinib, mycophenolate (MMF), methotrexate, rituximab, axatilimab, or imatinib who are unable to meet the following requirements: - No dose increases from 14 days prior to belumosudil initiation and continuing for the first 14 days of belumosudil treatment (dose reductions and discontinuations are permitted during this period) - Ability to discontinue these therapies within 14 days after initiating belumosudil (allowing for a maximum overlap period of up to 14 days with belumosudil treatment)
- Participants who meet any of the following criteria regarding systemic GVHD treatments:- Participants receiving other systemic GVHD treatments (apart from corticosteroids and calcineurin inhibitors) including investigational treatments who have not completed a washout period of at least 28 days or 5 half-lives (whichever is shorter) prior to the first dose of belumosudil. No washout period is required for extracorporeal photopheresis (ECP) or sirolimus therapy, but these must be discontinued before study treatment initiation. Note: Corticosteroids and calcineurin inhibitors may continue throughout the study.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Yet Recruiting | 30 Oct 2025 | 3 |
 France | Recruiting | 30 Oct 2025 | 3 |
 Germany | Not Yet Recruiting | 30 Oct 2025 | 3 |
 Italy | Recruiting | 30 Oct 2025 | 5 |
 The Netherlands | Not Yet Recruiting | 30 Oct 2025 | — |
 Spain | Not Yet Recruiting | 30 Oct 2025 | 5 |
| Netherlands | — | — | 4 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
belumosudil | Test | ORAL SUSPENSION | ORAL, NASOGASTRIC TUBE OR PERCUTANEOUS ENDOSCOPIC GASTROSTOMY TUBE USE | — | — | PRD12275526 |
SAR445761 - belumosudil | Test | FILM-COATED TABLET | ORAL | — | — | PRD10413339 |