BElumosudil for Bronchiolitis Obliterans Prevention/Therapy (BEBOP)
An Open-Label, Phase 2 Study to Evaluate the Activity of Belumosudil in Subjects With New Onset and Incipient Bronchiolitis Obliterans Syndrome Following Allogeneic Hematopoietic Cell Transplantation
1 other identifier
interventional
45
1 country
5
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)
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started May 2024
Typical duration for phase_2
5 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 3, 2023
CompletedFirst Posted
Study publicly available on registry
June 28, 2023
CompletedStudy Start
First participant enrolled
May 31, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2027
February 11, 2026
February 1, 2026
3.1 years
June 3, 2023
February 9, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
24-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.
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.
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.
up to 24 weeks.
Secondary Outcomes (5)
48-weeks Overall Response Rate (ORR) [Cohort A]
Evaluated every 8 weeks, up to 48 weeks.
48-week Progression Rate [Cohort B]
Evaluated every 8 weeks, up to 48 weeks.
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).
Chronic Graft Versus Host Disease (cGVHD) Response
Evaluated every 8 weeks, up to 48 weeks.
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).
Study Arms (2)
Cohort A: Belumosudil + Standard of Care Medications
EXPERIMENTAL30 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
EXPERIMENTAL15 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.
Interventions
Kinase inhibitor, tablet taken orally
Via inhalation by metered-dose inhaler.
Semi-synthetic macrolide antibiotic, taken orally
Leukotriene Receptor Antagonist, taken orally
Eligibility Criteria
You may qualify if:
- Diagnosis of BOS after HCT using pulmonary function testing, per the NIH diagnostic criteria17 OR the Atypical BOS criteria33 3.1.2.1 NIH Diagnostic Criteria for BOS. All of the following must be met:
- FEV1/VC \< 0.7 or \<5th percentile of predicted (FEV1 = Forced Expiratory Volume in 1 second; VC = Vital Capacity (either FVC, Forced Vital Capacity, or SVC, Slow Vital Capacity, whichever is greater)
- FEV1 \<75% of predicted with ≥ 10% absolute decline over less than 2 years. FEV1 should not correct to \>75% of predicted with albuterol, and the absolute decline for the corrected values should still remain ≥ 10% over 2 years.
- Absence of active infection in the respiratory tract, documented with investigations directed by clinical symptoms, such as chest radiographs or computed tomographic scans or microbiologic cultures (sinus aspiration, upper respiratory tract viral screen, sputum culture, bronchoalveolar lavage).
- One of the two supporting features of BOS:
- i - Evidence of air trapping by expiratory CT or small airway thickening or bronchiectasis by high-resolution chest CT OR
- ii - Evidence of air trapping by PFTs: RV (Residual Volume) \> 120% of predicted or RV/TLC elevated outside the 90% confidence interval (RV/Total Lung Capacity).
- Atypical Criteria for BOS:
- FEV1 \<80% of predicted with ≥ 10% absolute decline over the last 2 years or since transplant. The remote comparator can be an evaluation of PFTs done within 2 years of the PFTs assessment being evaluated to determine eligibility or the PFT assessment done prior to transplant.
- VC \< 80% of predicted.
- FEV1/VC \> 0.7.
- Absence of active infection in the respiratory tract, documented with investigations directed by clinical symptoms, such as chest radiographs or computed tomographic scans or microbiologic cultures (sinus aspiration, upper respiratory tract viral screen, sputum culture, bronchoalveolar lavage) or active non-infectious lung disease (such as interstitial lung disease) that explain spirometric changes or chest CT findings.
- Diagnosis of BOS-0p
- Decline in FEV1 of 10% - 19% of predicted compared with pretransplant testing OR
- Decline in predicted FEF25-75% (Forced Expiratory Flow between 25% and 75% of vital capacity) \> 25%
- +10 more criteria
You may not qualify if:
- Participants who have received prior therapy specifically for BOS. Therapy for cGVHD in the absence of BOS is permissible.
- Prior exposure to belumosudil.
- Participants who are receiving any other investigational immunosuppressive agents for cGVHD.
- Presence of an active uncontrolled infection. An active uncontrolled infection is defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs, or radiographic findings attributable to infection. Persistent fever without signs or symptoms will not be interpreted as an active uncontrolled infection.
- Known human immunodeficiency virus infection. Interactions between belumosudil and anti-retroviral agents have not been established.
- Active hepatitis B virus (HBV) or hepatitis C virus infection that requires treatment or at risk for HBV reactivation. At risk for HBV reactivation is defined as hepatitis B surface antigen positive or anti-hepatitis B core antibody positive. Subjects with previous positive serology results must have negative polymerase chain reaction results. Subjects whose immune status is unknown or uncertain must have results confirming immune status before enrollment.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)collaborator
- Sanoficollaborator
- Dana-Farber Cancer Institutelead
Study Sites (5)
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115, United States
Boston Children's Hospital
Boston, Massachusetts, 02215, United States
Brigham and Women's Hospital
Boston, Massachusetts, 02215, United States
University of Michigan
Ann Arbor, Michigan, 48109, United States
Fred Hutchinson Cancer Center
Seattle, Washington, 98109, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Corey Cutler, MD, MPH
Dana-Farber Cancer Institute
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
June 3, 2023
First Posted
June 28, 2023
Study Start
May 31, 2024
Primary Completion (Estimated)
June 30, 2027
Study Completion (Estimated)
December 31, 2027
Last Updated
February 11, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- Data can be shared no earlier than 1 year following the date of publication
- Access Criteria
- Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu
The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.