Ruxolitinib for Bronchiolitis Obliterans Syndrome (BOS) After Allogeneic Hematopoietic Cell Transplantation (HCT)

Inclusion Criteria:

* Diagnosis of BOS after HCT defined when all of the following criteria are met (as defined by the 2014 NIH criteria):

  * FEV1/VC \< 0.7 or the 5th percentile of predicted.
  * FEV1 = Forced Expiratory Volume in 1 second.
  * VC = Vital Capacity (Forced Vital Capacity "FVC" or Slow Vital Capacity "SVC", whichever is greater)
  * The 5th percentile of predicted is the lower limit of the 90% confidence interval.
  * For elderly patients, use the lower limits of normal defined according to NHANESIII calculations.
  * 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. The remote comparator would be an evaluation of PFTs done within 2 years of the PFTs assessment being evaluated to determine eligibility.
  * 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:
  * Evidence of air trapping by expiratory CT or small airway thickening or bronchiectasis by high-resolution chest CT OR
  * 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).
* Life expectancy \> 6 months at the time of enrollment as judged by the enrolling investigator.
* Male or female; 18-75 years old.
* ECOG Performance Status 0-2.
* At least 4 weeks since initiation of the most recent systemic therapy for cGVHD or BOS
* All females of childbearing potential must have a negative serum or urine pregnancy test \< 7 days before study drug administration.
* The ability to understand and willingness to sign a written consent document

Exclusion Criteria:

* Recurrent malignancy or disease progression requiring anticancer therapy.
* Currently receiving or have previously received ruxolitinib for chronic GVHD therapy.
* Known history of allergy to ruxolitinib or its excipients.
* Pregnant females or nursing mothers.
* Hepatic dysfunction: transaminases (ALT, AST) \> 5X ULN and/or total bilirubin \> 3X ULN.
* Hematologic dysfunction: absolute neutrophil count \<1000/μL, platelet cout \<50K, and/or Hgb \< 8 g/dL.
* Renal dysfunction: calculated creatinine clearance \< 40 mL/min (Cockcroft-Gault formula)
* Receipt of any non-FDA approved study medication within the last 4 weeks (This does not apply to use of FDA-approved drugs for an off-label indication).
* 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. Persisting fever without signs or symptoms will not be interpreted as an active uncontrolled infection.
* Known human immunodeficiency virus infection.
* 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.
* Severe organ dysfunction unrelated to underlying GVHD, including: Cholestatic disorders or unresolved veno-occlusive disease of the liver (defined as persistent bilirubin abnormalities not attributable to GVHD and ongoing organ dysfunction).
* Clinically significant or uncontrolled cardiac disease, including unstable angina, acute myocardial infarction within 6 months from Day 1 of study drug administration, New York Heart Association Class III or IV congestive heart failure, circulatory collapse requiring vasopressor or inotropic support, or arrhythmia that requires therapy.
* Clinically active asthma (variable and recurring symptoms of airflow obstruction and bronchial hyper-responsiveness), chronic obstructive pulmonary disease, interstitial lung disease, or cryptogenic organizing pneumonia or other causes of restrictive lung disease such as neuromuscular weakness or diaphragmatic paralysis.
* Any condition that, in the opinion of the investigator, would interfere with the subject's ability to comply with the study requirements.
* Uncontrolled substance abuse or psychiatric disorder.
* Deemed (by the local PI or the PFT lab) unable to reliably perform pulmonary function tests.
* Active smoker of cigarettes or marijuana.