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)
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).
i - Evidence of air trapping by expiratory CT or small airway thickening or bronchiectasis by high-resolution chest CT OR
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.
Parallel
Belumosudil
DrugKinase inhibitor, tablet taken orally
Fluticasone
DrugVia inhalation by metered-dose inhaler.
Azithromycin
DrugSemi-synthetic macrolide antibiotic, taken orally
Prednisone
DrugCorticosteroid, taken orally
Montelukast
DrugLeukotriene Receptor Antagonist, taken orally
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.
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.
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.
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.
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.
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.
Chronic Graft Versus Host Disease (cGVHD) Response
cGVHD response will be evaluated using non-pulmonary measurements per criteria of the 2014 NIH Consensus Conference.
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Dana-Farber Cancer Institute
Lead sponsor
Sanofi
Collaborator
National Heart, Lung, and Blood Institute (NHLBI)
Collaborator
