Chronic Graft-versus-host-diseasePhase 2NCT03640481
Efficacy and Safety of KD025 in Subjects With cGVHD After At Least 2 Prior Lines of Systemic Therapy
A Phase 2 study testing Belumosudil (KD025) in people with Chronic Graft-versus-host-disease, run by Kadmon, a Sanofi Company at 35 sites in United States.
Trial summary
This is a Phase 2, randomized, multicenter study to evaluate the efficacy and safety of KD025 in subjects with Chronic Graft Versus Host Disease (cGVHD) after at least 2 prior lines of systemic therapy Read more about this study
- Who is it for?
- Ages 12 years and olderHealthy volunteers can take part
- Conditions the study is for
- Chronic Graft-versus-host-disease
- What is being tested?
- Belumosudil (KD025)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 159 participants
- Where
- 35 sitesUnited States
- Study dates
- 11 Oct 2018to 11 Dec 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Male and female subjects at least 12 years of age who have had allogenic hematopoietic cell transplant (HCT).
- 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 Performance Score of ≥ 60 (if aged 16 years or older); Lansky Performance Score of ≥ 60 (if aged < 16 years)
- Weight ≥ 40kg
Who cannot join
- Subjects has not been on a stable dose / regimen of systemic cGVHD treatments for at least 2 weeks prior to screening. (Note: Concomitant corticosteroids, calcineurin inhibitors, sirolimus, MMF, methotrexate, rituximab, and extracorporeal photophoresis (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. Prior treatment with ibrutinib is allowed with a washout of at least 28 days prior to randomization.
Trial locations and contacts
35 sites in 1 country.
35 sites in 1 country
United States35 sites
CS Mott Children's Hospital Site Number : 157
Ann Arbor, Michigan, 48109-5718
Emory University School of Medicine Site Number : 100
Atlanta, Georgia, 30322
Augusta University Medical Center Site Number : 093
Augusta, Georgia, 30912
South Austin Medical Center Site Number : 091
Austin, Texas, 78704
Center for Cancer Research National Cancer Institute Site Number : 107
Bethesda, Maryland, 20892-1203
Massachusetts General Hospital Site Number : 002
Boston, Massachusetts, 02114
Dana-Farber Cancer Institute Site Number : 004
Boston, Massachusetts, 02215
University of Illinois at Chicago Site Number : 139
Chicago, Illinois, 60612
The Cleveland Clinic Foundation Site Number : 041
Cleveland, Ohio, 44195
James Cancer Hospital & Wexner Medical Center at the Ohio State University Comprehensive Cancer Center Site Number : 103
Columbus, Ohio, 43210
Colorado Blood Cancer Institute Site Number : 098
Denver, Colorado, 80218
Barbara Ann Karmanos Cancer Institute-4100 John R St Site Number : 094
Detroit, Michigan, 48201
City of Hope Medical Center Site Number : 050
Duarte, California, 91010
University of Kansas Cancer Center Site Number : 105
Fairway, Kansas, 66205
MD Anderson Cancer Center Site Number : 057
Houston, Texas, 77030-4009
University of Iowa Site Number : 126
Iowa City, Iowa, 52242
University of California, Los Angeles (UCLA) - Medical Center Site Number : 104
Los Angeles, California, 90059
University of Wisconsin - Carbone Cancer Center Site Number : 135
Madison, Wisconsin, 53792
University of Miami - Sylvester Cancer Center Site Number : 097
Miami, Florida, 33136
Froedtert Hospital and the Medical College of Wisconsin Site Number : 101
Milwaukee, Wisconsin, 53226
University of Minnesota Site Number : 051
Minneapolis, Minnesota, 55455
Sarah Cannon and HCA Research Institute Site Number : 007
Nashville, Tennessee, 37203
Vanderbilt University Medical Center Site Number : 063
Nashville, Tennessee, 37232-6868
Phoenix Childrens Hospital Site Number : 154
Phoenix, Arizona, 85016
University of Pittsburgh Medical Center (UPMC) - Hillman Cancer Center Site Number : 132
Pittsburgh, Pennsylvania, 15232
Oregon Health & Science University (OHSU) Site Number : 095
Portland, Oregon, 97239-3098
University of Rochester Site Number : 106
Rochester, New York, 14642
Texas Transplant Institute Site Number : 079
San Antonio, Texas, 78229
University of California, San Francisco (UCSF) - Helen Diller Family Comprehensive Cancer Center Site Number : 058
San Francisco, California, 94143
Fred Hutchinson Cancer Research Center Site Number : 052
Seattle, Washington, 98109
Washington University School of Medicine Site Number : 125
St Louis, Missouri, 63110
Stanford Cancer Center Site Number : 108
Stanford, California, 94305
Moffitt Site Number : 102
Tampa, Florida, 33612
University of Arizona - Cancer Center Site Number : 122
Tucson, Arizona, 85724
Wake Forest Site Number : 123
Winston-Salem, North Carolina, 27157
About this study
Official title: A Phase 2, Randomized, Multicenter Study to Evaluate the Efficacy and Safety of KD025 in Subjects With Chronic Graft Versus Host Disease (cGVHD) After At Least 2 Prior Lines of Systemic Therapy (The ROCKstar Study)
This is a Phase 2, randomized, multicenter study to evaluate the efficacy and safety of KD025 in subjects with Chronic Graft Versus Host Disease (cGVHD) after at least 2 prior lines of systemic therapy
Read the detailed description
Phase 2, open label, randomized, multicenter study in subjects with cGVHD who have previously been treated with at least 2 prior lines of systemic therapy. Approximately 166 subjects with active cGVHD will be randomized (1:1) to receive treatment with one of two belumosudil (formerly known as KD025) regimens:
- Arm A: belumosudil 200 mg QD
- Arm B: belumosudil 200 mg BID
With Amendment 2, the sample size was increased from approximately 126 subjects, with additional subjects to be enrolled as follows:
- 20 adolescents
- 20 adults into a site-specific Companion Study to collect biospecimens
These additional subjects will also be randomized (1:1) to Arm A or Arm B.
Any adolescent taking a proton pump inhibitor (PPI) or a strong CYP3A4 inducer will begin Cycle 1 Day 1 at the escalated dose of belumosudil 200 mg BID.
Randomization will be stratified according to prior cGVHD treatment with ibrutinib (Yes / No) and severe cGVHD at baseline (Yes / No). Subjects may receive treatment in 28-day treatment cycles until clinically significant progression of cGVHD. Subjects who have not achieved a response after 12 cycles of belumosudil should be withdrawn if in the Investigator's judgment there is no evidence of clinical benefit. Subjects will undergo evaluations as outlined in the Study Assessments table (Appendix A). The primary endpoint is the overall response rate (ORR) with responses as defined by the 2014 National Institute of Health (NIH) Consensus Development Project on clinical trials in cGVHD.
- Conditions
- Chronic Graft-versus-host-disease
- Being tested
- Belumosudil (KD025)
- Medical subject headings
- Bronchiolitis Obliterans Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Belumosudil (KD025)Drug
Also called REZUROCK
Belumosudil is an orally available Rho-associated protein kinase-2 (ROCK2) selective inhibitor.
| Study group | Role | What they receive |
|---|---|---|
| Arm A: belumosudil 200 mg, QD, adult arm | Experimental | Eligible subjects randomized to arm A will take belumosudil 200 mg once daily Receives: Drug: Belumosudil (KD025) |
| Arm B: belumosudil 200 mg, BID, adult arm | Experimental | Eligible subjects randomized to arm B will take belumosudil 200 mg twice daily Receives: Drug: Belumosudil (KD025) |
| Adolescent arm A: belumosudil 200 mg QD | Experimental | Eligible subjects randomized to arm A will take belumosudil 200 mg once daily Receives: Drug: Belumosudil (KD025) |
| Adolescent arm B: belumosudil 200 mg BID | Experimental | Eligible subjects randomized to arm B will take belumosudil 200 mg twice daily Receives: Drug: Belumosudil (KD025) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (ORR)
The ORR was defined as the percentage of participants with a best response meeting the overall response criteria assessment of complete response (CR) or partial response (PR) at any post-baseline response assessment. CR was defined as resolution of all manifestations of cGVHD in each organ or site. PR was defined as the improvement in at least one organ or site without progression in any other organ or site. Responses were assessed by the 2014 National Institutes of Health (NIH) Consensus Development Project on Clinical Trials in cGVHD.
Measured: From the date of randomization to the date of first documentation of progression or death due to any cause or data cut-off, whichever occurred first (maximum duration: up to 40.5 months for adult arms and 27.6 months for adolescent arms)
Secondary outcomes (15)
Duration of Response (DOR)
DOR is defined as the time from first documentation of response to the time of first documentation of deterioration from best response (e.g., CR to PR, or PR to Lack of response [LR]). CR was defined as resolution of all manifestations of cGVHD in each organ or site. PR was defined as the improvement in at least one organ or site without progression in any other organ or site. LR included the response status of mixed, unchanged, or progression. Mixed LR was defined as complete or partial response in at least one organ accompanied by progression in another organ. Unchanged LR was defined as outcomes that did not meet the criteria for complete response, partial response, progression or mixed response. Progression LR-P was defined as progression in at least one organ or site without a response in any other organ or site. Confidence interval (CI) is calculated using Kaplan-Meier method.
Measured: From the date of randomization to the date of first documentation of progression or death due to any cause or data cut-off, whichever occurred first (maximum duration: up to 40.5 months for adult arms and 27.6 months for adolescent arms)
Number of Participants With Improvement (>=7-Point Reduction [7-PtR] From Baseline) as Assessed by Lee Symptom Scale (LSS) Score
The questionnaire asked participants to indicate the degree of bother that they experienced due to symptoms in 7 domains potentially affected by chronic GVHD. It consists of 30 items of 7 domains: skin, eyes and mouth, breathing, eating and digestion, muscles and joints, energy, and mental and emotional. Each question is scored 0, 1, 2, 3 or 4. A domain score was calculated for each domain by taking the mean of all items completed if more than 50% were answered and normalizing to a 0 to 100 scale. A summary score was calculated as average of all non-missing domain scores if more than 50% of them were non-missing. A higher score indicated more bothersome symptoms. A 7-point difference on the summary score of cGVHD symptom scale was found to be clinically meaningful.
Measured: Baseline (Day 1) up to 40.5 months for adult arms; Baseline (Day 1) up to 27.6 months for adolescent arms
Number of Participants With Best Response by Organ System
The best response (CR, PR) for individual organs (skin, eyes, mouth, esophagus, upper gastrointestinal [GI], lower GI, liver, lungs, joints and fascia) were summarized. CR was defined as resolution of all manifestations of cGVHD in each organ or site. PR was defined as the improvement in at least one organ or site without progression in any other organ or site.
Measured: From date of randomization until disease progression or data cut-off, whichever occurred first (maximum duration: up to 40.5 months for adult arms and 27.6 months for adolescent arms)
Percentage of Participants With Best Response of PR and CR
PR was defined as the improvement in at least one organ or site without progression in any other organ or site. CR was defined as resolution of all manifestations of cGVHD in each organ or site. Responses were assessed by the 2014 NIH Consensus Development Project on Clinical Trials in cGVHD.
Measured: From the date of randomization to the date of first documentation of progression or death due to any cause or data cut-off, whichever occurred first (maximum duration: up to 40.5 months for adult arms and 27.6 months for adolescent arms)
Percent Change From Baseline in Corticosteroid Dose to Greatest Reduction
Change in corticosteroid doses was analyzed by using prednisone dose equivalents. If participants were not using prednisone as the systemic corticosteroid, then the prednisone dose equivalent would be determined according to following conversion ratios: 1 mg prednisone is equivalent to: 4.0 mg Hydrocortisone; 0.8 mg Methylprednisolone; 0.15 mg Dexamethasone; 1.0 mg Prednisolone and 0.8 mg Triamcinolone.
Measured: Baseline (Day 1) and 40.5 months for adult arms; Baseline (Day 1) and 27.6 months for adolescent arms
Percentage of Participants With Reduction and Discontinuation of Calcineurin Inhibitor Dose
Calcineurin inhibitors include systemic tacrolimus and cyclosporine. Percentage of participants with reduction and discontinuation of calcineurin inhibitor dose is presented.
Measured: Baseline (Day 1) up to 40.5 months for adult arms; Baseline (Day 1) up to 27.6 months for adolescent arms
Failure-Free Survival (FFS)
FFS was defined as the absence of new cGVHD systemic therapy, non-relapse mortality and recurrent malignancy (i.e. underlying disease) and was censored by last response assessment or long term follow up assessment, whichever was the latest and available.
Measured: From first dose of study drug to the time of first documentation of response or data cut-off, whichever occurred first (maximum duration: up to 40.5 months for adult arms and 27.6 months for adolescent arms)
Overall Survival (OS)
OS was defined as time from first dose of belumosudil to the date of death due to any cause.
Measured: From first dose of study drug to date of death from any cause or data cut-off, whichever occurred first (maximum duration: up to 40.5 months for adult arms and 27.6 months for adolescent arms)
Number of Participants With Best Response of Global Severity Rating Score as Based on the Clinician-Reported Global cGVHD Activity Assessment
The Clinician-reported global cGVHD Activity Assessment is a 0-10 point numeric rating scale with a score of 0 indicating "cGVHD symptoms not at all severe" and a score of 10 being "most severe cGVHD symptoms possible". Higher scores indicated worse symptoms. Best response was defined as PR+CR. PR was defined as the improvement in at least one organ or site without progression in any other organ or site. CR was defined as resolution of all manifestations of cGVHD in each organ or site. Participants were categorized in 3 categories at baseline based on the global severity scores of <6, =6-7 and >7 and number of participants with best response for them is reported.
Measured: Baseline (Day 1) up to 40.5 months for adult arms; Baseline (Day 1) up to 27.6 months for adolescent arms
Change From Baseline in Patient Self-Reported Symptom Activity Based on cGVHD Activity Assessment
The symptom activity item is a 0-10-point numeric rating scale with a score of 0 indicating "cGVHD symptoms not at all severe" and a score of 10 being "most severe cGVHD symptoms possible". The status reported by participants were categorized as none, mild, moderate, and severe. Higher scores indicated worse symptoms. Baseline was defined as the valid and last non-missing value obtained within 14 days prior to participants receiving the first study drug.
Measured: Baseline (Day 1) and 40.5 months for adult arms; Baseline (Day 1) and 27.6 months for adolescent arms
Maximum Concentration Observed (Cmax) of Belumosudil
Blood samples were collected at the specified timepoints to evaluate Cmax of belumosudil. As pre-specified in protocol, pharmacokinetic (PK) parameters were only calculated for participants with full PK samples. Thus, PK parameters were not calculated for adolescent participants who only had sparse PK samples.
Measured: Cycles 1 and 2: Pre-dose and 1, 2, 3, 4, 5, 6, 7, 8, and 12 hours post dose on Day 1 for adult arms; Cycles 2 and 4: Pre-dose and 3 and 5 hours post dose on Day 1 for adolescent arms
Observed Time to Reach Peak Plasma Concentration (Tmax) of Belumosudil
Blood samples were collected at the specified timepoints to evaluate Tmax of belumosudil. As pre-specified in protocol, PK parameters were only calculated for participants with full PK samples. Thus, PK parameters were not calculated for adolescent participants who only had sparse PK samples.
Measured: Cycles 1 and 2: Pre-dose and 1, 2, 3, 4, 5, 6, 7, 8, and 12 hours post dose on Day 1 for adult arms; Cycles 2 and 4: Pre-dose and 3 and 5 hours post dose on Day 1 for adolescent arms
Area Under the Curve Over Time Interval From 0 to 6 Hours (AUC0-6) of Belumosudil
Blood samples were collected at the specified timepoints to evaluate AUC0-6 of belumosudil. As pre-specified in protocol, PK parameters were only calculated for participants with full PK samples. Thus, PK parameters were not calculated for adolescent participants who only had sparse PK samples.
Measured: Cycles 1 and 2: Pre-dose and 1, 2, 3, 4, 5, 6, 7, 8, and 12 hours post dose on Day 1 for adult arms; Cycles 2 and 4: Pre-dose and 3 and 5 hours post dose on Day 1 for adolescent arms
Time to Response (TTR)
TTR was measured as the time from first treatment to the time of first documentation of response.
Measured: From first dose of study drug to the time of first documentation of response or data cut-off, whichever occurred first(maximum duration: up to 40.5 months for adult arms and 27.6 months for adolescent arms)
Time to Next Treatment (TTNT)
The TTNT was measured as the time from first treatment to the time of new systemic cGVHD treatment, censored by last response assessment or long term follow up assessment, whichever was the latest and available.
Measured: From first dose of study drug to the time of new treatment or censoring date, whichever occurred first (maximum duration: up to 40.5 months for adult arms and 27.6 months for adolescent arms)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2018
- Study start11 Oct 2018
- Primary completion11 Dec 2023
- Study completion11 Dec 2023
Why it stopped: The sponsor has decided to prematurely terminate the study due to the challenges encountered in recruiting adolescent participants. This decision was made without any safety concerns.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Chronic Graft-versus-host-diseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Phase 2, open label, randomized, multicenter study in subjects with cGVHD who have previously been treated with at least 2 prior lines of systemic therapy
- Masking
- None (open label)
- Enrolment
- 159 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kadmon, a Sanofi Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03640481
- Sponsor's protocol ID
- DRI17633
- Other IDs
- KD025-213, U1111-1279-2518, DRI17633
- Status last verified
- Nov 2024
- First submitted
- 13 Aug 2018
- Last updated
- 12 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org.
Publications
Przepiorka D, Le RQ, Ionan A, Li RJ, Wang YH, Gudi R, Mitra S, Vallejo J, Okusanya OO, Ma L, Yang Y, Patel P, Mezaache D, Shah R, Banerjee A, McLamore S, Maung AN, Goldberg KB, Pazdur R, Theoret MR, De Claro RA. FDA Approval Summary: Belumosudil for Adult and Pediatric Patients 12 Years and Older with Chronic GvHD after Two or More Prior Lines of Systemic Therapy. Clin Cancer Res. 2022 Jun 13;28(12):2488-2492. doi: 10.1158/1078-0432.CCR-21-4176.
PubMed 35135839Sharma R, Holtzman NG, Pusic I, Cutler C, Treister N, Mehta RS, Alousi AS, Vigneswaran N, Javaid A, Boksa F, Mody DP, Costa-da-Silva AC, Schueller O, Mace S, Yao Y, Ji R, Hu B, Marshall K, Blazar BR, Lee SJ, Pavletic SZ, Mays JW. Belumosudil reduces oral chronic graft-versus-host disease tissue inflammation and fibrosis: a ROCKstar companion study. Blood Adv. 2025 Jul 22;9(14):3479-3494. doi: 10.1182/bloodadvances.2025016170.
PubMed 40311075Lee SJ, Cutler C, Blazar BR, Tu A, Yang Z, Pavletic SZ. Correlation of Patient-Reported Outcomes with Clinical Organ Responses: Data from the Belumosudil Chronic Graft-versus-Host Disease Studies. Transplant Cell Ther. 2022 Oct;28(10):700.e1-700.e6. doi: 10.1016/j.jtct.2022.06.020. Epub 2022 Jul 1.
PubMed 35781099Cutler C, Lee SJ, Arai S, Rotta M, Zoghi B, Lazaryan A, Ramakrishnan A, DeFilipp Z, Salhotra A, Chai-Ho W, Mehta R, Wang T, Arora M, Pusic I, Saad A, Shah NN, Abhyankar S, Bachier C, Galvin J, Im A, Langston A, Liesveld J, Juckett M, Logan A, Schachter L, Alavi A, Howard D, Waksal HW, Ryan J, Eiznhamer D, Aggarwal SK, Ieyoub J, Schueller O, Green L, Yang Z, Krenz H, Jagasia M, Blazar BR, Pavletic S. Belumosudil for chronic graft-versus-host disease after 2 or more prior lines of therapy: the ROCKstar Study. Blood. 2021 Dec 2;138(22):2278-2289. doi: 10.1182/blood.2021012021.
PubMed 34265047
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Randomized, Multicenter Study to Evaluate the Efficacy and Safety of KD025 in Subjects With Chronic Graft Versus Host Disease (cGVHD) After At Least 2 Prior Lines of Systemic Therapy (The ROCKstar Study)
- ClinicalTrials.gov ID
- NCT03640481
- Acronym / sponsor ID
- DRI17633
- Conditions
- Chronic Graft-versus-host-disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The sponsor has decided to prematurely terminate the study due to the challenges encountered in recruiting adolescent participants. This decision was made without any safety concerns.
- Enrolment
- 159 participants (actual)
- Lead sponsor
- Kadmon, a Sanofi CompanyIndustry (pharma, biotech, devices)
- Study start
- 11 Oct 2018 (actual)
- Primary completion
- 11 Dec 2023 (actual)
- Study completion
- 11 Dec 2023 (actual)
- First posted
- 21 Aug 2018 (actual)
- Results
- Posted 12 Dec 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 2, randomized, multicenter study to evaluate the efficacy and safety of KD025 in subjects with Chronic Graft Versus Host Disease (cGVHD) after at least 2 prior lines of systemic therapy
Detailed description
Phase 2, open label, randomized, multicenter study in subjects with cGVHD who have previously been treated with at least 2 prior lines of systemic therapy. Approximately 166 subjects with active cGVHD will be randomized (1:1) to receive treatment with one of two belumosudil (formerly known as KD025) regimens:
- Arm A: belumosudil 200 mg QD
- Arm B: belumosudil 200 mg BID
With Amendment 2, the sample size was increased from approximately 126 subjects, with additional subjects to be enrolled as follows:
- 20 adolescents
- 20 adults into a site-specific Companion Study to collect biospecimens
These additional subjects will also be randomized (1:1) to Arm A or Arm B.
Any adolescent taking a proton pump inhibitor (PPI) or a strong CYP3A4 inducer will begin Cycle 1 Day 1 at the escalated dose of belumosudil 200 mg BID.
Randomization will be stratified according to prior cGVHD treatment with ibrutinib (Yes / No) and severe cGVHD at baseline (Yes / No). Subjects may receive treatment in 28-day treatment cycles until clinically significant progression of cGVHD. Subjects who have not achieved a response after 12 cycles of belumosudil should be withdrawn if in the Investigator's judgment there is no evidence of clinical benefit. Subjects will undergo evaluations as outlined in the Study Assessments table (Appendix A). The primary endpoint is the overall response rate (ORR) with responses as defined by the 2014 National Institute of Health (NIH) Consensus Development Project on clinical trials in cGVHD.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- Phase 2, open label, randomized, multicenter study in subjects with cGVHD who have previously been treated with at least 2 prior lines of systemic therapy
| Arm | Type | Receives |
|---|---|---|
| Arm A: belumosudil 200 mg, QD, adult arm | Experimental | Drug: Belumosudil (KD025)Eligible subjects randomized to arm A will take belumosudil 200 mg once daily |
| Arm B: belumosudil 200 mg, BID, adult arm | Experimental | Drug: Belumosudil (KD025)Eligible subjects randomized to arm B will take belumosudil 200 mg twice daily |
| Adolescent arm A: belumosudil 200 mg QD | Experimental | Drug: Belumosudil (KD025)Eligible subjects randomized to arm A will take belumosudil 200 mg once daily |
| Adolescent arm B: belumosudil 200 mg BID | Experimental | Drug: Belumosudil (KD025)Eligible subjects randomized to arm B will take belumosudil 200 mg twice daily |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Male and female subjects at least 12 years of age who have had allogenic hematopoietic cell transplant (HCT).
- 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 Performance Score of ≥ 60 (if aged 16 years or older); Lansky Performance Score of ≥ 60 (if aged < 16 years)
Key exclusion criteria (3 listed)
- Subjects has not been on a stable dose / regimen of systemic cGVHD treatments for at least 2 weeks prior to screening. (Note: Concomitant corticosteroids, calcineurin inhibitors, sirolimus, MMF, methotrexate, rituximab, and extracorporeal photophoresis (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. Prior treatment with ibrutinib is allowed with a washout of at least 28 days prior to randomization.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Belumosudil (KD025)Also: REZUROCKBelumosudil is an orally available Rho-associated protein kinase-2 (ROCK2) selective inhibitor. | Drug | Adolescent arm A: belumosudil 200 mg QD, Adolescent arm B: belumosudil 200 mg BID, Arm A: belumosudil 200 mg, QD, adult arm, Arm B: belumosudil 200 mg, BID, adult arm |
Primary outcome
Overall Response Rate (ORR)
Time frame: From the date of randomization to the date of first documentation of progression or death due to any cause or data cut-off, whichever occurred first (maximum duration: up to 40.5 months for adult arms and 27.6 months for adolescent arms)
The ORR was defined as the percentage of participants with a best response meeting the overall response criteria assessment of complete response (CR) or partial response (PR) at any post-baseline response assessment. CR was defined as resolution of all manifestations of cGVHD in each organ or site. PR was defined as the improvement in at least one organ or site without progression in any other organ or site. Responses were assessed by the 2014 National Institutes of Health (NIH) Consensus Development Project on Clinical Trials in cGVHD.
15 secondary outcomes
Duration of Response (DOR)
Time frame: From the date of randomization to the date of first documentation of progression or death due to any cause or data cut-off, whichever occurred first (maximum duration: up to 40.5 months for adult arms and 27.6 months for adolescent arms)
Number of Participants With Improvement (>=7-Point Reduction [7-PtR] From Baseline) as Assessed by Lee Symptom Scale (LSS) Score
Time frame: Baseline (Day 1) up to 40.5 months for adult arms; Baseline (Day 1) up to 27.6 months for adolescent arms
Number of Participants With Best Response by Organ System
Time frame: From date of randomization until disease progression or data cut-off, whichever occurred first (maximum duration: up to 40.5 months for adult arms and 27.6 months for adolescent arms)
Percentage of Participants With Best Response of PR and CR
Time frame: From the date of randomization to the date of first documentation of progression or death due to any cause or data cut-off, whichever occurred first (maximum duration: up to 40.5 months for adult arms and 27.6 months for adolescent arms)
Percent Change From Baseline in Corticosteroid Dose to Greatest Reduction
Time frame: Baseline (Day 1) and 40.5 months for adult arms; Baseline (Day 1) and 27.6 months for adolescent arms
Percentage of Participants With Reduction and Discontinuation of Calcineurin Inhibitor Dose
Time frame: Baseline (Day 1) up to 40.5 months for adult arms; Baseline (Day 1) up to 27.6 months for adolescent arms
Failure-Free Survival (FFS)
Time frame: From first dose of study drug to the time of first documentation of response or data cut-off, whichever occurred first (maximum duration: up to 40.5 months for adult arms and 27.6 months for adolescent arms)
Overall Survival (OS)
Time frame: From first dose of study drug to date of death from any cause or data cut-off, whichever occurred first (maximum duration: up to 40.5 months for adult arms and 27.6 months for adolescent arms)
Number of Participants With Best Response of Global Severity Rating Score as Based on the Clinician-Reported Global cGVHD Activity Assessment
Time frame: Baseline (Day 1) up to 40.5 months for adult arms; Baseline (Day 1) up to 27.6 months for adolescent arms
Change From Baseline in Patient Self-Reported Symptom Activity Based on cGVHD Activity Assessment
Time frame: Baseline (Day 1) and 40.5 months for adult arms; Baseline (Day 1) and 27.6 months for adolescent arms
Maximum Concentration Observed (Cmax) of Belumosudil
Time frame: Cycles 1 and 2: Pre-dose and 1, 2, 3, 4, 5, 6, 7, 8, and 12 hours post dose on Day 1 for adult arms; Cycles 2 and 4: Pre-dose and 3 and 5 hours post dose on Day 1 for adolescent arms
Observed Time to Reach Peak Plasma Concentration (Tmax) of Belumosudil
Time frame: Cycles 1 and 2: Pre-dose and 1, 2, 3, 4, 5, 6, 7, 8, and 12 hours post dose on Day 1 for adult arms; Cycles 2 and 4: Pre-dose and 3 and 5 hours post dose on Day 1 for adolescent arms
Area Under the Curve Over Time Interval From 0 to 6 Hours (AUC0-6) of Belumosudil
Time frame: Cycles 1 and 2: Pre-dose and 1, 2, 3, 4, 5, 6, 7, 8, and 12 hours post dose on Day 1 for adult arms; Cycles 2 and 4: Pre-dose and 3 and 5 hours post dose on Day 1 for adolescent arms
Time to Response (TTR)
Time frame: From first dose of study drug to the time of first documentation of response or data cut-off, whichever occurred first(maximum duration: up to 40.5 months for adult arms and 27.6 months for adolescent arms)
Time to Next Treatment (TTNT)
Time frame: From first dose of study drug to the time of new treatment or censoring date, whichever occurred first (maximum duration: up to 40.5 months for adult arms and 27.6 months for adolescent arms)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 35135839Przepiorka D, Le RQ, Ionan A, Li RJ, Wang YH, Gudi R, Mitra S, Vallejo J, Okusanya OO, Ma L, Yang Y, Patel P, Mezaache D, Shah R, Banerjee A, McLamore S, Maung AN, Goldberg KB, Pazdur R, Theoret MR, De Claro RA. FDA Approval Summary: Belumosudil for Adult and Pediatric Patients 12 Years and Older with Chronic GvHD after Two or More Prior Lines of Systemic Therapy. Clin Cancer Res. 2022 Jun 13;28(12):2488-2492. doi: 10.1158/1078-0432.CCR-21-4176.
- Derived from this study: PubMed 40311075Sharma R, Holtzman NG, Pusic I, Cutler C, Treister N, Mehta RS, Alousi AS, Vigneswaran N, Javaid A, Boksa F, Mody DP, Costa-da-Silva AC, Schueller O, Mace S, Yao Y, Ji R, Hu B, Marshall K, Blazar BR, Lee SJ, Pavletic SZ, Mays JW. Belumosudil reduces oral chronic graft-versus-host disease tissue inflammation and fibrosis: a ROCKstar companion study. Blood Adv. 2025 Jul 22;9(14):3479-3494. doi: 10.1182/bloodadvances.2025016170.
- Derived from this study: PubMed 35781099Lee SJ, Cutler C, Blazar BR, Tu A, Yang Z, Pavletic SZ. Correlation of Patient-Reported Outcomes with Clinical Organ Responses: Data from the Belumosudil Chronic Graft-versus-Host Disease Studies. Transplant Cell Ther. 2022 Oct;28(10):700.e1-700.e6. doi: 10.1016/j.jtct.2022.06.020. Epub 2022 Jul 1.
- Derived from this study: PubMed 34265047Cutler C, Lee SJ, Arai S, Rotta M, Zoghi B, Lazaryan A, Ramakrishnan A, DeFilipp Z, Salhotra A, Chai-Ho W, Mehta R, Wang T, Arora M, Pusic I, Saad A, Shah NN, Abhyankar S, Bachier C, Galvin J, Im A, Langston A, Liesveld J, Juckett M, Logan A, Schachter L, Alavi A, Howard D, Waksal HW, Ryan J, Eiznhamer D, Aggarwal SK, Ieyoub J, Schueller O, Green L, Yang Z, Krenz H, Jagasia M, Blazar BR, Pavletic S. Belumosudil for chronic graft-versus-host disease after 2 or more prior lines of therapy: the ROCKstar Study. Blood. 2021 Dec 2;138(22):2278-2289. doi: 10.1182/blood.2021012021.
- Individual participant dataSharing planned: Yes. Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
35 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Belumosudil (KD025) in people with Chronic Graft-versus-host-disease, run by Kadmon, a Sanofi Company at 35 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 12 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 35 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response Rate (ORR) (time frame: From the date of randomization to the date of first documentation of progression or death due to any cause or data cut-off, whichever occurred first (maximum duration: up to 40.5 months for adult arms and 27.6 months for adolescent arms)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03640481, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Dec 2024.