A Study to Test an Oral Medicine, Belumosudil, in Combination With Corticosteroids in Participants at Least 12 Years of Age With Newly Diagnosed Chronic Graft Versus Host Disease.
Belumosudil: Pharmaceutical form:Tablet-Route of administration:oral
Placebo: Pharmaceutical form:Table-Route of administration:oral
Prednisone: Pharmaceutical form:Tablet-Route of administration:oral
Prednisolone: Pharmaceutical form:Tablet-Route of administration:oral
Study summary
This is a parallel, Phase 3, two-arm study for the treatment of newly diagnosed moderate or severe chronic GVHD.
The study duration for a participant includes up to 4 weeks for screening; a treatment period until clinically meaningful cGVHD progression (defined as progression requiring addition of new systemic treatment for cGVHD), relapse/recurrence of the underlying disease, participant starts new systemic treatment for cGVHD or experiences an unacceptable toxicity, at the request of the participants or the investigators, or until the end of study is reached, whichever comes first; at least 30 days follow-up of adverse events (AEs) after the last dose until resolution or stabilization, if applicable; and long-term follow-up until death or study close-out, whichever comes first.
Eligibility
Sex
ALL
Min age
12 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
* Patients must be at least 12 years of age inclusive, at the time of signing the informed consent
* Participants who have undergone allogenic HCT with newly diagnosed moderate to severe cGVHD according to NIH consensus diagnosis and staging criteria (2014)
* Participants who require systemic treatment with corticosteroids for cGVHD
* Participants who have not received any prior systemic treatment for cGVHD (including ECP)
* If participants are receiving other immunosuppressive agents for the prophylaxis or treatment of acute GVHD, the dose should be under the threshold pre-defined in protocol
* For adult participants, the body weight should be ≥40 kg. For adolescent participants, the body weight should be ≥30 kg
* Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
* Participants or their legally authorized representative must be capable of giving signed informed consent
Exclusion Criteria:
Participants are excluded from the study if any of the following criteria apply:
Medical conditions
* Any evidence (histologic, cytogenetic, molecular, hematologic, or mixed) of progressive or relapsed underlying disease after the most recent allogeneic HCT
* Post-transplant lymphoproliferative disease within 4 weeks prior to randomization
* Female participants who are pregnant or breastfeeding
* Unable to tolerate a prednisone equivalent dose of corticosteroids ≥ 1 mg/kg/day Prior/concomitant therapy
* Participant has had previous exposure to belumosudil.
* Received any previous systemic treatment for cGVHD with the following exception: Corticosteroids for cGVHD received within 7 days prior to the planned administration of IMP only if in the interest of participant.
Prior/concurrent clinical study experience
* Received any investigational agents, or any investigational device or procedure, or prohibited therapy for this study within 28 days or 5 elimination half-lives prior to randomization, whichever is longer Diagnostic assessments
* Karnofsky (if aged ≥16 years)/Lansky (if aged \<16 years) Performance Score of \< 60
* Platelets \<25 x 109/L. Platelet transfusion is not allowed within 3 days before the screening hematological test
* Absolute neutrophil count (ANC) \<0.5 x 109/L. The use of granulocyte-colony stimulating factor (G-CSF) is not allowed to reach this level during screening
* Estimated Glomerular Filtration Rate (eGFR) \<30 mL/min/1.73 m2 using the MDRD-4 variable formula (if aged ≥18 years) or using the Bedside Schwartz formula (if aged \<18 years)
* Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \>3 x ULN without liver cGVHD or\>5 × ULN with liver) cGVHD
* Total bilirubin \>1.5 × (ULN) (\>3 × ULN if Gilbert syndrome)
* Participant has forced expiratory volume in 1 second (FEV1) of predicted ≤39% or has lung score of 3 according to NIH consensus diagnostic and staging criteria (2014)
* 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)
* Known history of human immunodeficiency virus (HIV)
* Active viral disease including hepatitis B virus (HBV) or hepatitis C virus (HCV)
* Active uncontrolled cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infection. Infections are considered controlled if appropriate therapy has been instituted and, at the time of screening, no signs of infection worsening are present according to Investigator's judgement
* Diagnosed or treated for another malignancy other than the underlying disease allogeneic HCT was indicated for, within 3 years prior to randomization with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in-situ malignancy, or low risk prostate cancer after curative therapy
* Unable to swallow tablets
* Participant 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
* Any active, uncontrolled infections assessed to be clinically significant by the Investigator
Primary outcome measure(s)
Event-Free Survival (EFS) — Until the end of the study (up to 2.5 years since first patient in). From the date of randomization to the date of any predefined event, whichever occurs first
Trial sites (151)
Facility
City
Region
Status
University of Arkansas for Medical Sciences-Site Number : 8400019
Little Rock
Arkansas
City of Hope National Medical Center- Site Number : 8400001
Duarte
California
University of California San Francisco - Parnassus Heights- Site Number : 8400035
San Francisco
California
AdventHealth Orlando- Site Number : 8400023
Orlando
Florida
The Hope Clinic of Emory University- Site Number : 8400020
Decatur
Georgia
Northwestern University- Site Number : 8400017
Chicago
Illinois
Indiana University Health University Hospital- Site Number : 8400006
Indianapolis
Indiana
University of Kentucky Chandler Medical Center- Site Number : 8400024
Lexington
Kentucky
Johns Hopkins Hospital- Site Number : 8400033
Baltimore
Maryland
Dana Farber Cancer Institute Site Number : 8400005
Boston
Massachusetts
Karmanos Cancer Institute - Detroit- Site Number : 8400013
Detroit
Michigan
UNC Children's Hospital- Site Number : 8400025
Chapel Hill
North Carolina
Atrium Health Wake Forest Baptist Medical Center - Winston-Salem - Medical Center Boulevard- Site Number : 8400007
Winston-Salem
North Carolina
Oncology Hematology Care - Kenwood- Site Number : 8400030
Cincinnati
Ohio
The Ohio State University Comprehensive Cancer Center (OSUCCC) - The James Cancer Hospital and Solove Research Institute- Site Number : 8400026
Columbus
Ohio
Oregon Health and Science University- Site Number : 8400027
Portland
Oregon
UPMC Hillman Cancer Center- Site Number : 8400008
Pittsburgh
Pennsylvania
Sarah Cannon Research Institute Site Number : 8400003
Nashville
Tennessee
St. David's South Austin Medical Center- Site Number : 8400002
Austin
Texas
Texas Oncology - Dallas - Worth Street- Site Number : 8400010
Dallas
Texas
Texas Transplant Institute - Methodist Hospital- Site Number : 8400037
San Antonio
Texas
University of Virginia Comprehensive Cancer Center-Site Number : 8400031
Charlottesville
Virginia
Fred Hutchinson Cancer Research Center- Site Number : 8400004
Seattle
Washington
University of Wisconsin Carbone Cancer Center-Site Number : 8400029
Madison
Wisconsin
Investigational Site Number : 0320006
Pilar
Buenos Aires
Investigational Site Number : 0320005
Buenos Aires
Argentina
Investigational Site Number : 0320003
Buenos Aires
Argentina
Investigational Site Number : 0320001
Buenos Aires
Argentina
Investigational Site Number : 0320002
Buenos Aires
Argentina
Investigational Site Number : 0320004
Córdoba
Argentina
Investigational Site Number : 0360005
Westmead
New South Wales
Investigational Site Number : 0360003
Brisbane
Queensland
Investigational Site Number : 0360001
Melbourne
Victoria
Investigational Site Number : 0360004
Murdoch
Western Australia
Investigational Site Number : 0400003
Graz
Austria
Investigational Site Number : 0400001
Linz
Austria
Investigational Site Number : 0400004
Vienna
Austria
Cliniques Universitaires St. Luc-Investigational Site Number : 0560005
Woluwe
Brussels Capital
UZ Leuven-Investigational Site Number : 0560001
Leuven
Vlaams-Brabant
Investigational Site Number : 0560006
Bruges
Belgium
+ 111 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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