A Study of Belumosudil in Children With Chronic Graft Versus Host Disease (schoolROCK)

Purpose

This is an open-label, single group, Phase 1/2, 1-arm study for treatment of children aged 1 to <18 years with active moderate-to-severe cGVHD that is refractory to or recurred after at least 2 prior lines of systemic therapy for cGVHD. The purpose of Phase 1 is to determine the PK profiles and to establish the Recommended Pediatric Equivalent Dose (RPED) of belumosudil in participants aged 1 to <12 years with active moderate to severe cGVHD. Upon completion and evaluation of Phase 1, Phase 2 will commence with the purpose of determining safety and efficacy (ORR by 24 weeks) of belumosudil in participants aged 1 to <18 years. Study details include: The end of study is defined as 3 years after the last participant is recruited or all participants have discontinued treatment, or have died, whichever comes first. Minimum of 6 participants ages 1 to 6 years will be enrolled for each phase of study Individual participant duration on study will consist of: Up to 4 weeks for screening. Treatment until clinically significant progression of cGVHD, relapse/recurrence of the underlying disease, start of a new systemic treatment for cGVHD, experience of an unacceptable adverse event, request from participant or Investigator, or until the end of the study is reached, whichever comes first. 4 weeks of post treatment safety follow-up. Long-term follow-up until death or end of study, whichever occurs first.

Condition

  • Chronic Graft Versus Host Disease

Eligibility

Eligible Ages
Between 1 Year and 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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. - 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) or Karnofsky (if aged >16) 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 - Life expectancy of >6 months - Participants can take the IMP orally or via a nasogastric tube

Exclusion Criteria

  • Progressive underlying disease or post-transplant lymphoproliferative disease within 4 weeks prior to the first dose of the IMP. - Diagnosed with another malignancy (other than malignancy for which transplant was performed) within 3 years prior to the first dose of the IMP - 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 - Current treatment with systemic agents for cGVHD (apart from corticosteroids and calcineurin inhibitors), such as ibrutinib, ruxolitinib, sirolimus, mycophenolate (MMF), methotrexate, rituximab, imatinib, extracorporeal photopheresis (ECP) and any investigational cGVHD treatment. Prior treatment with these agents and/or therapy is allowed with a washout of at least 28 days or 5 half-lives, whichever is shorter, prior to the first dose of the IMP - 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 - 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 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) - 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 - 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

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
N/A
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
belumosudil 		Participant will take IMP with a meal approximately the same time each morning. IMP dose will be according to weight and will be increased to daily dose of twice a day (BID) in participants who concomitantly receive proton pump inhibitors (PPIs) or strong CYP3A4 inducers. No concomitant PPIs are allowed during Phase 1 up to and including Cycle 1 Day 15. From Day 16 onwards, PPIs will be permitted, resulting in an increased dose of Belumosudil to BID. No concomitant strong CYP3A4 inducers are allowed during Phase 1.
  • Drug: Belumosudil
    Pharmaceutical form:Oral suspension -Route of administration:Oral or nasogastric tube
    Other names:
    • SAR445761
    • REZUROCK
  • Drug: Belumosudil
    Pharmaceutical form:Tablet formulation-Route of administration:Oral
    Other names:
    • SAR445761
    • REZUROCK

Recruiting Locations

Memorial Sloan Kettering Cancer Center - New York - York Avenue- Site Number : 8400001
New York 5128581, New York 5128638 10065

More Details

Status
Recruiting
Sponsor
Sanofi

Study Contact

Trial Transparency email recommended (Toll free for US & Canada)
800-633-1610
contact-us@sanofi.com