TerminatedPhase 2

Ruxolitinib for Early Lung Dysfunction After Hematopoietic Stem Cell Transplant

Stopped: Study closed due to slow enrollment.

United States7 participantsStarted 2021-11-12

Plain-language 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.

Who can participate

Age range5 Years – 60 Years

SexALL

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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

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 …

What they're measuring

Number of participants with ruxolitinib treatment response

Timeframe: 6 months from early lung dysfunction diagnosis

Trial details

NCT IDNCT04908735

SponsorChildren's Hospital Medical Center, Cincinnati

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2025-09-17