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

NCT03674047 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 18-265
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 7

Brief Summary

This research study is studying a drug as a possible treatment for Bronchiolitis Obliterans Syndrome (BOS) after having an Allogeneic Hematopoietic Cell Transplantation (HCT).

Conditions

Other Cancer

Keywords

Hematopoietic Cell Transplantation

Outcome Measures

Primary Outcomes (2)

• absolute FEV1 increase

  The proportion of participants with a sustained, absolute FEV1 increase by ≥ 10% after 3 months of treatment with ruxolitinib (compared to baseline measure prior to study enrollment) among participants with newly diagnosed Bronchiolitis Obliterans Syndrome BOS.

  3 Months

• treatment failure, comparing 3-month FEV1 to baseline FEV1

  The proportion of participants who do not experience a sustained, absolute decrease in FEV1 by ≥ 10% after 3 months of treatment with ruxolitinib (compared to baseline measure prior to study enrollment) among participants with established Bronchiolitis Obliterans Syndrome BOS.

  3 Months

Secondary Outcomes (6)

• Change scores for PFT measurements

  1 Year

• Improvements in chronic GVHD organ manifestations

  3 and 6 Months

• Overall survival

  2 Years

• cGVHD progression-free survival

  2 Years

• The incidence and types of serious adverse events

  From the start of treatment until 30 days after the end of treatment, up to 13 months total

Study Arms (2)

newly-diagnosed BOS

EXPERIMENTAL

-Participants will take ruxolitinib twice every day

Drug: ruxolitinib

Established BOS

EXPERIMENTAL

-Participants will take ruxolitinib twice every day

Drug: ruxolitinib

Interventions

ruxolitinib DRUG

Ruxolitinib blocks certain proteins called tyrosine kinases. Specifically, it blocks tyrosine kinases called JAK2. it's believe that ruxolitinib may lower the rate of GVHD through its ability to block the JAK2 pathway since this pathway can lead to inflammation in the body

Also known as: Jakafi

Established BOS; newly-diagnosed BOS

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Incyte Corporation: collaborator

Study Sites (7)

City of Hope Cancer Center

Duarte, California, 91010, United States

Location

H. Lee Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• DeFilipp Z, Kim HT, Cheng GS, Hamilton BK, Chhabra S, Hamadani M, Sandhu KS, Perez L, Lee CJ, Brennan TL, Garrelts C, Brown BM, Gallagher K, Newcomb RA, El-Jawahri A, Chen YB. A phase 2 multicenter trial of ruxolitinib to treat bronchiolitis obliterans syndrome after allogeneic HCT. Blood Adv. 2025 Jan 28;9(2):244-253. doi: 10.1182/bloodadvances.2024014000.

  PMID: 39365992 DERIVED

MeSH Terms

Interventions

ruxolitinib

Study Officials

• Zachariah DeFilipp, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

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: September 14, 2018
• First Posted: September 17, 2018
• Study Start: April 19, 2019
• Primary Completion: December 2, 2022
• Study Completion: December 1, 2025
• Last Updated: November 10, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)