40 Participants Needed

Ruxolitinib for Lung Dysfunction Post Stem Cell Transplant

(HSCT Trial)

Recruiting at 1 trial location
SL
EN
Overseen ByEvelyn Nguyen, MS
Age: < 65
Sex: Any
Trial Phase: Phase 2
Sponsor: Children's Hospital Medical Center, Cincinnati
Must be taking: Flovent, Montelukast, Steroids, Ruxolitinib
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 2 JurisdictionsThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are taking investigational agents for GVHD, you must stop them at least 30 days before starting the trial treatment.

What data supports the effectiveness of the drug Ruxolitinib for lung dysfunction after stem cell transplant?

Ruxolitinib has shown effectiveness in reducing symptoms and improving outcomes in patients with myelofibrosis undergoing stem cell transplants, and it has been used successfully to treat lung issues in transplant patients when reintroduced after discontinuation. This suggests it may help with lung dysfunction post-transplant by reducing inflammation and improving overall transplant outcomes.12345

Is Ruxolitinib generally safe for humans?

Ruxolitinib has been used in various conditions and is generally considered safe, but it can cause side effects like anemia (low red blood cell count) and thrombocytopenia (low platelet count), which are usually manageable. There have been reports of infections and breathing problems when stopping the drug, so careful monitoring is important.24678

How is the drug Ruxolitinib unique for treating lung dysfunction after stem cell transplant?

Ruxolitinib is unique because it is an oral medication that inhibits the Janus kinase (JAK) pathway, which is involved in immune function and inflammation. This mechanism may help manage lung dysfunction after stem cell transplant, although it is primarily used for conditions like myelofibrosis and can increase the risk of infections.29101112

Research Team

KM

Kasiani Myers, MD

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Eligibility Criteria

This trial is for people aged 5 to 60 who've had a bone marrow transplant and are showing early signs of lung problems. They need good blood, kidney, and liver function. It's not for those allergic to the study drug, pregnant or breastfeeding individuals without birth control, or anyone treated with other experimental drugs for graft-versus-host disease in the last month.

Inclusion Criteria

I am between 5 and 60 years old and have had a stem cell transplant with early lung issues.
My kidneys are working well enough (CrCl ≥ 30 mL/min).
My blood tests for immune cells, clotting, and platelets are within normal ranges.
See 1 more

Exclusion Criteria

I currently have a lung infection that is not under control.
I am not pregnant, breastfeeding, or at risk of becoming pregnant or fathering a child, or I can use effective birth control.
Known hypersensitivity to any constituent of the study medication
See 1 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive early treatment with Flovent/montelukast, steroids, and ruxolitinib to reverse lung injury

24 weeks
Regular visits for monitoring lung function

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

  • Ruxolitinib
Trial Overview The trial tests if adding Ruxolitinib to standard treatments like Flovent/montelukast and steroids can reverse early lung damage after a stem cell transplant. The goal is to prevent chronic lung issues or severe Bronchiolitis Obliterans by treating it sooner.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Ruxolitinib TreatmentExperimental Treatment1 Intervention

Ruxolitinib is already approved in United States, European Union for the following indications:

🇺🇸
Approved in United States as Jakafi for:
  • Intermediate or high-risk myelofibrosis
  • Polycythemia vera
  • Steroid-refractory acute graft-versus-host disease
  • Chronic graft-versus-host disease
  • Vitiligo
🇪🇺
Approved in European Union as Jakavi for:
  • Intermediate or high-risk myelofibrosis
  • Polycythemia vera
  • Steroid-refractory acute graft-versus-host disease
  • Chronic graft-versus-host disease
  • Non-segmental vitiligo

Find a Clinic Near You

Who Is Running the Clinical Trial?

Children's Hospital Medical Center, Cincinnati

Lead Sponsor

Trials
844
Recruited
6,566,000+

Findings from Research

In a study of 14 patients with myelofibrosis who received allogeneic hematopoietic cell transplantation after treatment with ruxolitinib, 71.4% experienced relief from myelofibrosis-related symptoms, and 64% had a significant reduction in spleen size.
Ruxolitinib treatment prior to transplantation was associated with a high engraftment rate of 93% and may improve outcomes by reducing inflammatory cytokines, potentially lowering the risk of graft failure and acute graft-versus-host disease.
Allogeneic hematopoietic cell transplantation for myelofibrosis in patients pretreated with the JAK1 and JAK2 inhibitor ruxolitinib.Jaekel, N., Behre, G., Behning, A., et al.[2021]
Ruxolitinib, an oral JAK1/2 inhibitor, is effective in reducing spleen size and symptom burden in patients with intermediate and high-risk myelofibrosis, making it a valuable treatment option before hematopoietic stem cell transplantation (HSCT).
The impact of ruxolitinib on HSCT outcomes is not well understood, and there is significant variability in how it is used in patients transitioning to HSCT, highlighting the need for more research to guide treatment protocols.
Peritransplantation Use of Ruxolitinib in Myelofibrosis.Ibrahim, U., Petrone, GEM., Mascarenhas, J., et al.[2021]
In a study of 551 myelofibrosis patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT), those who were pretreated with the JAK1/2 inhibitor ruxolitinib (RUX) showed a higher leukocyte engraftment rate (94%) compared to those who did not respond to RUX (85%).
Patients with ongoing spleen response at the time of transplantation after RUX treatment had a significantly lower risk of relapse (8.1% vs. 19.1%) and better 2-year event-free survival (68.9% vs. 53.7%), indicating that RUX pretreatment can be beneficial without negatively impacting transplantation outcomes.
Impact of prior JAK-inhibitor therapy with ruxolitinib on outcome after allogeneic hematopoietic stem cell transplantation for myelofibrosis: a study of the CMWP of EBMT.Kröger, N., Sbianchi, G., Sirait, T., et al.[2022]

References

Allogeneic hematopoietic cell transplantation for myelofibrosis in patients pretreated with the JAK1 and JAK2 inhibitor ruxolitinib. [2021]
Peritransplantation Use of Ruxolitinib in Myelofibrosis. [2021]
Impact of prior JAK-inhibitor therapy with ruxolitinib on outcome after allogeneic hematopoietic stem cell transplantation for myelofibrosis: a study of the CMWP of EBMT. [2022]
Hypoxemic Respiratory Failure Following Ruxolitinib Discontinuation in Allogeneic Hematopoietic Cell Transplantation Recipients. [2021]
Compassionate use of ruxolitinib in acute and chronic graft versus host disease refractory both to corticosteroids and extracorporeal photopheresis. [2022]
Case-report: EBV driven lymphoproliferative disorder associated with Ruxolitinib. [2022]
Ruxolitinib versus standard therapy for the treatment of polycythemia vera. [2022]
Interim analysis of safety and efficacy of ruxolitinib in patients with myelofibrosis and low platelet counts. [2021]
Pneumocystis jiroveci pneumonitis complicating ruxolitinib therapy. [2022]
10.United Statespubmed.ncbi.nlm.nih.gov
Mycobacterial Infections With Ruxolitinib: A Retrospective Pharmacovigilance Review. [2021]
Ruxolitinib for the treatment of myelofibrosis: its clinical potential. [2021]
Fedratinib: a pharmacotherapeutic option for JAK-inhibitor naïve and exposed patients with myelofibrosis. [2022]