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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
37
Pharmaceutical form:Oral suspension -Route of administration:Oral or nasogastric tube
Pharmaceutical form:Tablet formulation-Route of administration:Oral
Memorial Sloan Kettering Cancer Center- Site Number : 8400001
New York, New York, United States
RECRUITINGTexas Children's Hospital - Baylor - PIN- Site Number : 8400008
Houston, Texas, United States
RECRUITINGInvestigational Site Number : 0560003
Ghent, Belgium
RECRUITINGInvestigational Site Number : 0560001
Leuven, Belgium
RECRUITINGInvestigational Site Number : 1560001
Shanghai, China
RECRUITINGInvestigational Site Number : 1560004
Shenzhen, China
RECRUITINGInvestigational Site Number : 1560002
Suzhou, China
RECRUITINGInvestigational Site Number : 2500002
Marseille, France
RECRUITINGInvestigational Site Number : 2500001
Paris, France
RECRUITINGInvestigational Site Number : 2760001
Berlin, Germany
RECRUITING...and 10 more locations
Phase 1: AUC
PK parameter (AUC at steady state)
Time frame: Cycle 1 Day 15 after the last participant dosed in the phase 1 part.
Proportion of participants who achieve an overall response (partial response [PR] or complete response [CR]) by Week 25 or Cycle 7 Day 1 whichever is first
Proportion of participants who achieve an overall response (partial response \[PR\] or complete response \[CR\]) by Week 25 or Cycle 7 Day 1 whichever is first, as defined by the National Institute of Health (NIH) Consensus response criteria
Time frame: Up to 3 years after the last participant enrolled
Phase 1: Number of participants with treatment-emergent adverse events [TEAEs], serious TEAEs, and adverse events of special interest (AESIs)
Safety
Time frame: Up to 3 years after the last participant enrolled
Phase 1: Cmax
Steady-state belumosudil PK parameters
Time frame: Cycle 1 Day 15 after the last participant dosed in the phase 1 part
Phase 1: AUC0-6h
Steady-state belumosudil PK parameters
Time frame: Cycle 1 Day 15 after the last participant dosed in the phase 1 part
Phase 1: ORR
Proportion of participants who achieve an overall response (complete response \[CR\] or partial response \[PR\]) by 24 weeks, as defined by the 2014 National Institute of Health (NIH) Consensus response criteria
Time frame: Up to 3 years after the last participant enrolled
Phase 1: DOR
Time from the date of first response to the date of progression of cGVHD, initiation of a new systemic treatment for cGVHD, or death, whichever comes first. DOR is determined only for participants who achieved overall response (PR or CR) as per 2014 NIH Consensus response criteria
Time frame: Up to 3 years after the last participant enrolled
Phase 1: response by organ
As defined by the 2014 NIH Consensus response criteria
Time frame: Up to 3 years after the last participant enrolled
Phase 1: failure-free survival (FFS)
Time from the date of the first investigational medicinal product (IMP) administration to the date of initiation of a new systemic treatment for cGVHD, relapse or recurrence of the underlying disease, or death, whichever occurs first
Time frame: Up to 3 years after the last participant enrolled
Phase 1: overall survival (OS)
Time from the date of first IMP administration to the date of death due to any cause
Time frame: Up to 3 years after the last participant enrolled
Phase 1: time to response (TTR)
Time from the date of the first IMP administration to the first documented response (either CR or PR) according to the 2014 NIH Consensus Criteria for cGVHD
Time frame: Up to 3 years after the last participant enrolled
Phase 2: Number of participants with treatment-emergent adverse events [TEAEs], serious TEAEs, and adverse events of special interest (AESIs)
Safety
Time frame: Up to 3 years after the last participant enrolled
Phase 2: Ctrough of belumosudil
Time frame: Cycle 2 Day 1 and Cycle 4 Day 1 after the last participant enrolled
Phase 2: DOR
Time from first response to the date of progression of cGVHD, initiation of a new systemic treatment for cGVHD, or death, whichever comes first. DOR is determined only for participants who achieved overall response (PR or CR) as per NIH Consensus response criteria
Time frame: Up to 3 years after the last participant enrolled
Phase 2: response by organ
response by organ as defined by the 2014 NIH Consensus response criteria
Time frame: Up to 3 years after the last participant enrolled
Phase 2: FFS
Time from the date of the first IMP administration to the date of initiation of a new systemic treatment for cGVHD, relapse or recurrence of the underlying disease, or death, whichever occurs first
Time frame: Up to 3 years after the last participant enrolled
Phase 2: OS
Time from the date of first IMP administration to the date of death due to any cause
Time frame: Up to 3 years after the last participant enrolled
Phase 2: time to response (TTR)
Time from the date of the first IMP administration to the first documented response (either CR or PR) according to the 2014 NIH Consensus Criteria for cGVHD
Time frame: Up to 3 years after the last participant enrolled
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