Ruxolitinib for Newly Diagnosed Bronchiolitis Obliterans Syndrome

Hematologic Malignancy Clinical Trial

Official title:

Ruxolitinib for Newly Diagnosed Bronchiolitis Obliterans Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05413356
• Other study ID #: ZJU-HSCT-BOS
• Status: Recruiting
• Phase: Phase 2
• Start date: June 1, 2022
• Est. completion date: January 1, 2025

Study information

• Verified date: May 2022
• Source: First Affiliated Hospital of Zhejiang University
• Contact: Yi Luo, M.D.
• Phone: +86057187233801
• Email: luoyijr[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Lung is one of the target organs in chronic graft versus host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Bronchiolitis obliterans syndrome (BOS) after allo-HSCT was a clinical syndrome characterized by persistent airflow restriction which is the result of lung cGVHD. BOS is one of the main causes of late mortality after allo-HSCT, severely restricting the daily activities and respiratory function of patients. It limits the quality of life and increased the non-relapse mortality (NRM) after allo-HSCT. Currently, the first-line treatment for BOS is FAM ( oral fluticasone, azithromycin and montelukast). However, more than 50% of patients develop as steroids resistant (SR)-BOS, and SR-BOS has a poor prognosis and irreversible impaired lung function. Ruxolitinib is an effective drug in the treatment of SR-cGVHD. This is a phase Ⅱ prospective clinical study to explore the efficacy and safety of ruxolitinib as a first-line treatment for newly diagnosed BOS after allo-HSCT.

Description:

The incidence of chronic graft versus host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) was 30%-70%, Which extremely limited the quality of life and the survival of patients after allo-HSCT. Lung is one of the target organs in cGVHD after allo-HSCT. Bronchiolitis obliterans syndrome (BOS) after allo-HSCT was a clinical syndrome characterized by persistent airflow restriction which is the result of lung cGVHD. BOS is one of the main causes of late mortality after allo-HSCT, severely restricting the daily activities and respiratory function of patients. It limits the quality of life and increased the non-relapse mortality (NRM) after allo-HSCT. Currently, the first-line treatment for BOS is FAM ( oral fluticasone, azithromycin and montelukast). However, more than 50% of patients develop as steroids resistant (SR)-BOS, and SR-BOS has a poor prognosis and irreversible impaired lung function. Ruxolitinib is an effective drug in the treatment of SR-cGVHD. This is a phase Ⅱ prospective clinical study to explore the efficacy and safety of ruxolitinib as a first-line treatment for newly diagnosed BOS after allo-HSCT.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: January 1, 2025
• Est. primary completion date: June 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Male or female; 18-65 years old

2. Diagnosis of BOS after allo-HCT defined as the 2014 NIH criteria

3. Life expectancy > 6 months at the time of enrollment

4. At least 4 weeks since initiation of the most recent systemic therapy for cGVHD or BOS

5. The ability to understand and willingness to sign a written consent document

Exclusion Criteria:

1. Recurrent malignancy or disease progression requiring anticancer therapy

2. Currently receiving or have previously received ruxolitinib for chronic GVHD therapy

3. Known history of allergy to ruxolitinib or its excipients

4. Hepatic dysfunction: transaminases (ALT, AST) > 5X ULN and/or total bilirubin > 3X ULN

5. Hematologic dysfunction: absolute neutrophil count <1000/µL, platelet cout <30*10E9/L, and/or Hgb < 8 g/dL

6. Renal dysfunction: calculated creatinine clearance < 30 mL/min (Cockcroft-Gault formula)

7. previously received second-line treatment or any drugs in clinical trials for cGVHD

Related Conditions & MeSH terms

• Bronchiolitis
• Bronchiolitis Obliterans
• Bronchiolitis Obliterans Syndrome
• Hematologic Malignancy
• Hematologic Neoplasms
• Syndrome

Intervention

Drug:
• Ruxolitinib
Oral ruxolitinib twice daily

Locations

Country	Name	City	State
China	The first Affiliated Hospital of Zhejiang University	Hangzhou	Zhejiang

Sponsors (12)

Lead Sponsor

Collaborator

First Affiliated Hospital of Zhejiang University

First Affiliated Hospital of Wenzhou Medical University, Jinhua Central Hospital, Ningbo No. 1 Hospital, Second Affiliated Hospital, School of Medicine, Zhejiang University, Sir Run Run Shaw Hospital, Taizhou Hospital, The Affiliated People's Hospital of Ningbo University, The First Affiliated Hospital of Zhejiang Chinese Medical University, Union hospital of Fujian Medical University, Xiangya Hospital of Central South University, Zhejiang Provincial People's Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	3 Months
Secondary	treatment failure rate	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)	3 Months
Secondary	absolute FEV1 increase	The proportion of participants with a sustained, absolute FEV1 increase by = 10% after treatment with ruxolitinib (compared to baseline measure prior to study enrollment)	6 Months, 9 Months, 12 Months and 24 Months
Secondary	Improvements in chronic GVHD organ specific manifestations	mprovements in chronic GVHD organ specific manifestations will be categorized according to the NIH chronic GVHD consensus criteria.	6 Months, 9 Months, 12 Months and 24 Months
Secondary	Overall Survival	The proportion of patients survival at two years after enrollment of ruxolitinib treatment	2 years
Secondary	cGVHD progression-free survival	Participants alive without cGVHD progression are censored at the date of last disease evaluation	2 years
Secondary	The incidence and types of serious adverse events	Adverse events are graded according to Common Terminology Criteria for Adverse Events (CTCAE v4)	From the start of treatment until 30 days after the end of treatment, up to 2 years
Secondary	The change of systemic corticosteroid dose over time	The change of systemic corticosteroid dose over time during the treatment of BOS	From the start of treatment until the end of treatment, up to 2 years