The goal of this research study is to test the efficacy of a novel immunosuppressive agent, belumosudil, in allogeneic hematopoietic stem cell transplant (HSCT) recipients who have been newly diagnosed or have developing (early stage) bronchiolitis obliterans syndrome (BOS). The name of the study drugs involved in this study are: * Belumosudil (an immunotherapy) * Fluticasone (an intranasal corticosteroid) * Azithromycin (an antibiotic) * Montelukast (a leukotriene receptor antagonist) * Prednisone (a corticosteroid)
This is an open-label, single-arm, single-stage phase 2 study to evaluate the activity of Belumosudil in subjects with new onset of bronchiolitis obliterans syndrome (BOS) (Cohort A) and for subjects with incipient BOS (Cohort B) following allogeneic hematopoietic cell transplantation (HCT). Belumosudil is a novel immunosuppressive agent that has both immunosuppressive activity as well as antifibrotic (slowing down the rate of fibrosis or scarring in the lungs) properties. Participants will be placed into one of two treatment groups: Group A Belumosudil + standard of care medications for BOS versus Group B Belumosudil only. The U.S. Food and Drug Administration (FDA) has not approved belumosudil for the initial or preventative therapy of BOS, but it has been approved for the treatment of Chronic Graft Versus Host Disease (cGVHD). The other study drugs, Fluticasone, Azithromycin, Montelukast, and Prednisone are FDA approved as standard of care drugs for BOS. Study procedures include screening for eligibility, treatment visits, blood tests, pulmonary function tests, bronchoscopy wit bronchoalveolar lavage, and Computed Tomography (CT) Scans. Participants will receive study treatment for 11 months (48 weeks) and will be followed for an additional 12 months after completion of study treatment. It is expected that about 45 people (30 in Group A and 15 in Group B) will take part in this research study. The National Heart, Lung, and Blood Institute (NHLBI) is supporting this research study by providing funding. Sanofi is supporting this research study by providing study drug, Belumosudil.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
45
Kinase inhibitor, tablet taken orally
Via inhalation by metered-dose inhaler.
Semi-synthetic macrolide antibiotic, taken orally
Corticosteroid, taken orally
Leukotriene Receptor Antagonist, taken orally
Stanford University School of Medicine
Stanford, California, United States
RECRUITINGDana-Farber Cancer Institute
Boston, Massachusetts, United States
RECRUITINGBoston Children's Hospital
Boston, Massachusetts, United States
NOT_YET_RECRUITINGBrigham and Women's Hospital
Boston, Massachusetts, United States
NOT_YET_RECRUITINGUniversity of Michigan
Ann Arbor, Michigan, United States
RECRUITINGFred Hutchinson Cancer Center
Seattle, Washington, United States
RECRUITING24-week Overall Response Rate (ORR) [Cohort A]
24-week ORR defined as the proportion of participants achieving BOS complete response (CR) or partial response (PR) based on change in FEV1 measurement per criteria of the 2014 NIH Consensus Conference.
Time frame: up to 24 weeks.
24-week Overall Response Rate (ORR) [Cohort B]
24-week ORR defined as the proportion of participants achieving BOS complete response (CR) or partial response (PR) based on change in FEV1 measurement per criteria of the 2014 NIH Consensus Conference.
Time frame: up to 24 weeks.
24-week Progression Rate [Cohort B]
24-week progression rate is defined as the proportion of participants experiencing BOS progression based on change in FEV1 measurement per criteria of the 2014 NIH Consensus Conference.
Time frame: up to 24 weeks.
48-weeks Overall Response Rate (ORR) [Cohort A]
48-week ORR defined as the proportion of participants achieving BOS complete response (CR) or partial response (PR) based on change in FEV1 measurement per criteria of the 2014 NIH Consensus Conference.
Time frame: Evaluated every 8 weeks, up to 48 weeks.
48-week Progression Rate [Cohort B]
48-week progression rate is defined as the proportion of participants experiencing BOS progression based on change in FEV1 measurement per criteria of the 2014 NIH Consensus Conference.
Time frame: Evaluated every 8 weeks, up to 48 weeks.
Grade 3-5 Treatment-Related Toxicity Rate
All grade 3-5 AEs with attribution of probably, possibly or definitely-related to treatment based on CTCAEv5 as reported on case report forms were counted. Rate is the proportion of treated participants experiencing at least one treatment-related grade 3-5 AE of any type during the time of observation.
Time frame: Evaluated on cycle 1 day 15, cycle 2, 3, 5, 7, 9, 11 (cycle duration=4 weeks) and end of treatment. Observed on treatment up to 12 cycles (48 weeks).
Chronic Graft Versus Host Disease (cGVHD) Response
cGVHD response will be evaluated using non-pulmonary measurements per criteria of the 2014 NIH Consensus Conference.
Time frame: Evaluated every 8 weeks, up to 48 weeks.
Lee Symptom Scale (LSS) Quality of Life (QOL) Score
Mean and standard deviation Lee Symptom Scale Quality of Life score estimated at each assessment timepoint. The LSS QOL scale is a 30-item measure with answers ranging from 0 "Not at All" to 4 "Extremely." Higher scores indicate greater symptom burden.
Time frame: Evaluated on cycle 1 day 15, cycle 2, 3, 5, 7, 9, 11 (cycle duration=4 weeks) and end of treatment. Observed on treatment up to 12 cycles (48 weeks).
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