Moderate to severe steroid-refractory or steroid-dependent chronic GVHD. cGVHD
Conditions
Interventions
Single-arm, open-label study in which all patients are administered belumosudil at the protocol-specified dose.
cGVHD
belumosudil
Sponsors
Yoshihiro Inamoto
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Patients who have received sufficient explanation regarding participation in this study, have adequately understood the study, and have provided written informed consent of their own free will prior to any study specific procedures. 2.Patients who are 18 years of age or older at the time of obtaining informed consent. 3.Patients diagnosed with chronic graft versus host disease after allogeneic hematopoietic cell transplantation, fulfilling the 2014 National Institutes of Health diagnostic criteria. 4.Patients with moderate to severe chronic graft versus host disease according to the 2014 National Institutes of Health global severity scoring system. 5.Patients with an inadequate response to first line systemic corticosteroid therapy for chronic graft versus host disease who are planned to receive second line systemic treatment. Patients who develop chronic graft versus host disease fulfilling the National Institutes of Health criteria during tapering of corticosteroids administered for acute graft versus host disease may be considered as having received first line corticosteroid therapy for chronic graft versus host disease. Eligible patients must meet at least one of the following conditions at the time of enrollment. A. Steroid refractory chronic graft versus host disease Disease progression despite treatment with prednisolone or equivalent at a dose of 0.5 to 1.0 mg per kg per day for at least 7 consecutive days. No clinical improvement after treatment with prednisolone or equivalent at a dose of 0.5 mg per kg per day or 1.0 mg per kg every other day for at least 4 consecutive weeks. Inability to taper prednisolone or equivalent below 0.5 mg per kg per day or 1.0 mg per kg every other day due to disease flare or recurrence of symptoms. B. Steroid dependent chronic graft versus host disease Inability to taper prednisolone or equivalent below 0.25 mg per kg per day or 0.5 mg per kg every other day.
Exclusion criteria
Exclusion criteria: 1.Patients with relapse or progression of the underlying disease at the time of enrollment. 2.Patients with post-transplant lymphoproliferative disorder (PTLD) or other lymphoproliferative disorders (LPD). 3.Patients with a life expectancy of less than 24 weeks, as assessed by the investigator. 4.Patients who are intolerant to systemic corticosteroid therapy. 5.Patients who have received third-line or later systemic therapy for chronic GVHD. 6.Patients who received systemic therapy other than corticosteroids and calcineurin inhibitors as initial systemic treatment for chronic GVHD. 7.Patients who are currently receiving investigational drugs or participating in another interventional clinical trial at the time of enrollment. 8.Patients with a history of malignancy other than the underlying disease diagnosed within the past 3 years, except for malignancies considered cured with no evidence of recurrence, as judged by the investigator. 9.Patients with a history of hypersensitivity to any component of this drug, pregnant women, or women who may be pregnant 10. Patients who are deemed inappropriate for study participation by the principal investigator or sub-investigators for any other reason.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall response rate (ORR) at Week 24 of study drug administration. | — |
Secondary
| Measure | Time frame |
|---|---|
| ORR at weeks 12, 24, 48, 72, 96, 120, 144, 168, and 192 after the start of study drug administration Organ-specific response at weeks 12, 24, 48, 72, 96, 120, 144, 168, and 192 after the start of study drug administration Best ORR at weeks 12, 24, 48, 72, 96, 120, 144, 168, and 192 after the start of study drug administration Best organ-specific response at weeks 12, 24, 48, 72, 96, 120, 144, 168, and 192 after the start of study drug administration Duration of response (DOR) Time to response (TTR) Change from baseline to week 24 after the start of study drug administration in the Lee Chronic GVHD Symptom Scale score ORR based on the Lee Chronic GVHD Symptom Scale at week 24 after the start of study drug administration Organ-specific response based on the Lee Chronic GVHD Symptom Scale at week 24 after the start of study drug administration Changes in corticosteroid dose over time and discontinuation of corticosteroids Reduction in corticosteroid dose Status of non-corticosteroid immunosuppressant use over time and discontinuation of these agents Time to next treatment (TTNT) (between all treatment lines) Failure-free survival (FFS) Overall survival (OS) Cumulative incidence of relapse or recurrence of the primary disease Non-relapse mortality (NRM) Proportion of subjects with a response duration of 20 weeks or longer Change in Performance Status (PS) Percent predicted forced expiratory volume in 1 second (%predicted FEV1) and FEV1/FVC ratio Frequency, timing, and outcome of serious adverse events (SAEs) | — |
Contacts
Public ContactMorishita Takanobu
Fujita Helath University Hospital
Outcome results
None listed