BElumosudil for Bronchiolitis Obliterans Prevention/Therapy (BEBOP)
- Conditions
- Lung DiseasesBronchiolitis ObliteransChronic Graft Versus Host DiseaseBronchiolitis Obliterans Syndrome
- Interventions
- Registration Number
- NCT05922761
- Lead Sponsor
- Dana-Farber Cancer Institute
- Brief Summary
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)
- Detailed Description
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 45
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort A: Belumosudil + Standard of Care Medications Belumosudil 30 participants with bronchiolitis obliterans syndrome (BOS) will complete study procedures as follows: * Drug diary * CT scans at Cycles 3 and 7 and at End of Treatment. * Cycle 1 * Day 1 - 28 of 28-day cycle: Predetermined dose of Belumosudil 1x daily. * Predetermined doses of Fluticasone, Montelukast, and Prednisone 1x daily. * Predetermined dose of azithromycin 3 days per treatment week. * Cycle 2 - 3 * Day 1 - 28 of 28-day cycle: Predetermined dose of Belumosudil 1x daily. * Predetermined doses of Fluticasone Montelukast 1x daily. Predetermined doses of Prednisone 1x daily at treating physician's discretion. * Predetermined dose of azithromycin 3 days per treatment week. * Cycle 4 - 12 * Day 1 - 28 of 28-day cycle: Predetermined dose of Belumosudil 1x daily. * Predetermined doses of Fluticasone and Montelukast 1x daily. * Predetermined dose of azithromycin 3 days per treatment week. Cohort A: Belumosudil + Standard of Care Medications Fluticasone 30 participants with bronchiolitis obliterans syndrome (BOS) will complete study procedures as follows: * Drug diary * CT scans at Cycles 3 and 7 and at End of Treatment. * Cycle 1 * Day 1 - 28 of 28-day cycle: Predetermined dose of Belumosudil 1x daily. * Predetermined doses of Fluticasone, Montelukast, and Prednisone 1x daily. * Predetermined dose of azithromycin 3 days per treatment week. * Cycle 2 - 3 * Day 1 - 28 of 28-day cycle: Predetermined dose of Belumosudil 1x daily. * Predetermined doses of Fluticasone Montelukast 1x daily. Predetermined doses of Prednisone 1x daily at treating physician's discretion. * Predetermined dose of azithromycin 3 days per treatment week. * Cycle 4 - 12 * Day 1 - 28 of 28-day cycle: Predetermined dose of Belumosudil 1x daily. * Predetermined doses of Fluticasone and Montelukast 1x daily. * Predetermined dose of azithromycin 3 days per treatment week. Cohort A: Belumosudil + Standard of Care Medications Azithromycin 30 participants with bronchiolitis obliterans syndrome (BOS) will complete study procedures as follows: * Drug diary * CT scans at Cycles 3 and 7 and at End of Treatment. * Cycle 1 * Day 1 - 28 of 28-day cycle: Predetermined dose of Belumosudil 1x daily. * Predetermined doses of Fluticasone, Montelukast, and Prednisone 1x daily. * Predetermined dose of azithromycin 3 days per treatment week. * Cycle 2 - 3 * Day 1 - 28 of 28-day cycle: Predetermined dose of Belumosudil 1x daily. * Predetermined doses of Fluticasone Montelukast 1x daily. Predetermined doses of Prednisone 1x daily at treating physician's discretion. * Predetermined dose of azithromycin 3 days per treatment week. * Cycle 4 - 12 * Day 1 - 28 of 28-day cycle: Predetermined dose of Belumosudil 1x daily. * Predetermined doses of Fluticasone and Montelukast 1x daily. * Predetermined dose of azithromycin 3 days per treatment week. Cohort A: Belumosudil + Standard of Care Medications Prednisone 30 participants with bronchiolitis obliterans syndrome (BOS) will complete study procedures as follows: * Drug diary * CT scans at Cycles 3 and 7 and at End of Treatment. * Cycle 1 * Day 1 - 28 of 28-day cycle: Predetermined dose of Belumosudil 1x daily. * Predetermined doses of Fluticasone, Montelukast, and Prednisone 1x daily. * Predetermined dose of azithromycin 3 days per treatment week. * Cycle 2 - 3 * Day 1 - 28 of 28-day cycle: Predetermined dose of Belumosudil 1x daily. * Predetermined doses of Fluticasone Montelukast 1x daily. Predetermined doses of Prednisone 1x daily at treating physician's discretion. * Predetermined dose of azithromycin 3 days per treatment week. * Cycle 4 - 12 * Day 1 - 28 of 28-day cycle: Predetermined dose of Belumosudil 1x daily. * Predetermined doses of Fluticasone and Montelukast 1x daily. * Predetermined dose of azithromycin 3 days per treatment week. Cohort A: Belumosudil + Standard of Care Medications Montelukast 30 participants with bronchiolitis obliterans syndrome (BOS) will complete study procedures as follows: * Drug diary * CT scans at Cycles 3 and 7 and at End of Treatment. * Cycle 1 * Day 1 - 28 of 28-day cycle: Predetermined dose of Belumosudil 1x daily. * Predetermined doses of Fluticasone, Montelukast, and Prednisone 1x daily. * Predetermined dose of azithromycin 3 days per treatment week. * Cycle 2 - 3 * Day 1 - 28 of 28-day cycle: Predetermined dose of Belumosudil 1x daily. * Predetermined doses of Fluticasone Montelukast 1x daily. Predetermined doses of Prednisone 1x daily at treating physician's discretion. * Predetermined dose of azithromycin 3 days per treatment week. * Cycle 4 - 12 * Day 1 - 28 of 28-day cycle: Predetermined dose of Belumosudil 1x daily. * Predetermined doses of Fluticasone and Montelukast 1x daily. * Predetermined dose of azithromycin 3 days per treatment week. Cohort B: Belumosudil Belumosudil 15 participants with signs concerning developing BOS will complete study procedure as follows: * Drug diary * CT scans at Cycles 3 and 7 and at End of Treatment. * Cycle 1 - 12 - Day 1 - 28 of 28-day cycle: Predetermined dose of Belumosudil 1x daily.
- Primary Outcome Measures
Name Time Method 24-week Overall Response Rate (ORR) [Cohort B] up to 24 weeks. 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.
24-week Overall Response Rate (ORR) [Cohort A] up to 24 weeks. 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.
24-week Progression Rate [Cohort B] up to 24 weeks. 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.
- Secondary Outcome Measures
Name Time Method Grade 3-5 Treatment-Related Toxicity Rate 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). 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.
Chronic Graft Versus Host Disease (cGVHD) Response Evaluated every 8 weeks, up to 48 weeks. cGVHD response will be evaluated using non-pulmonary measurements per criteria of the 2014 NIH Consensus Conference.
Lee Symptom Scale (LSS) Quality of Life (QOL) Score 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). 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.
48-weeks Overall Response Rate (ORR) [Cohort A] Evaluated every 8 weeks, up to 48 weeks. 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.
48-week Progression Rate [Cohort B] Evaluated every 8 weeks, up to 48 weeks. 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.
Trial Locations
- Locations (5)
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Fred Hutchinson Cancer Center
🇺🇸Seattle, Washington, United States