Ruxolitinib for Early Lung Dysfunction After Hematopoietic Stem Cell Transplant

NCT ID: NCT04908735

Last Updated: 2025-12-16

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-12
• Study Completion Date: 2028-11-30

Brief Summary

Hematopoietic stem cell transplant (HSCT) is an effective but toxic therapy, and lung injury affects as many as 25% of children receiving HSCT. Improved transplant techniques and major improvements in survival mean that HSCT is being more widely used, and more mismatched grafts are being used. Bronchiolitis obliterans (BO) is a major limitation of pediatric HSCT success as BO is commonly diagnosed late in children, when lung injury is irreversible, leading to long term morbidity or even death. Currently, there are major gaps in our knowledge regarding incidence, etiology and optimal treatment of BO following HSCT, and important diagnostic limitations specific to children. Diagnosis of BO is usually based on performance of pulmonary function tests, which is usually impossible in ill children under 10. Even older children who feel unwell or un-cooperative may be unable to produce interpretable data. These deficiencies in diagnosis mean that BO is commonly diagnosed late, meaning fibrosis has occurred and lesions are irreversible.

The hypothesis for this interventional trial is that early treatment with standard Flovent/montelukast and steroids plus ruxolitinib will reverse lung injury and reduce the frequency of chronic pulmonary impairment or florid BO.

Conditions

Hematopoietic Stem Cell Transplant (HSCT); Bronchiolitis Obliterans (BO)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ruxolitinib Treatment

Group Type: EXPERIMENTAL

Ruxolitinib

Intervention Type: DRUG

Participants will receive ruxolitinib orally twice daily for 24 weeks.

Interventions

Ruxolitinib

Participants will receive ruxolitinib orally twice daily for 24 weeks.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Subjects ≥ 5 years and ≤ 60 years of age who have undergone allogeneic HCT AND exhibit early lung dysfunction as defined by any one of the following:

• >10% decrease in FEV1 from baseline or decrease of 25% of FEF 25-75 from baseline
• active GVHD in another organ system + pulmonary symptoms (Tachypnea without wheezing, new oxygen requirement, cough)
• Increased R5 by 50% by clinical oscillometry
• Air trapping on CT, small airway thickening, or bronchiectasis

AND - All age groups, including adults:

Adequate renal function defined as estimated Creatinine Clearance (CrCl) ≥ 30 mL/min as calculated by the cystatin c GFR or nuclear GFR

Adequate hepatic function as defined by:

• ALT and AST ≤ 5 x ULN, unless the ALT / AST increase is due to cGVHD
• Total bilirubin of ≤ 5 x ULN (unless of non-hepatic origin or due to Gilbert's Syndrome) or Total bilirubin of < 10 x ULN if due to GVHD

Adequate hematological function defined as:

• Absolute neutrophil count ≥1.0 x 10^9/L
• Platelets ≥30 x 10^9/L

PT/INR <2 x ULN and PTT (aPTT) < 2 x ULN (unless abnormalities are unrelated to coagulopathy or bleeding disorder)

Exclusion Criteria

• Known hypersensitivity to any constituent of the study medication.
• Active uncontrolled pulmonary infection (preceding infectious evaluation including bronchoscopy as clinically indicated)
• Subjects who are pregnant or breastfeeding or are at risk of pregnancy or fathering a baby and are unable to use acceptable highly effective method of birth control (e.g., implants, injectables, combined oral contraceptives, some intrauterine devices [IUDs], complete abstinence or sterilized partner) and a barrier method (e.g., condoms, cervical ring, sponge, etc.) during the period of therapy and for 90 days for both females and males after the last dose of study drug.
• Subjects previously treated with investigational agent for GVHD within the 30 days prior to first dose of study treatment. Other non-GVHD additional investigational agents may be allowed on a case by case basis with review/approval by the study Lead PI.

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Children's Hospital Medical Center, Cincinnati

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kasiani Myers, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital Medical Center, Cincinnati

Locations

University of Minnesota

Minneapolis, Minnesota, United States

Site Status: RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status: RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Sara Loveless, BSN, RN

Role: CONTACT

Sara.Loveless@cchmc.org

(513) 803-7656

Facility Contacts

Jen Braun

Role: primary

danie659@umn.edu

612-625-0084

Sara Loveless, BSN, RN

Role: primary

Sara.Loveless@cchmc.org

513-803-7656

Alex Caraballo, MS

Role: primary

CTTSSupportiveCare@chop.edu

585-472-1738

Other Identifiers

2020-0719

Identifier Type: -

Identifier Source: org_study_id