Ruxolitinib for Newly Diagnosed Bronchiolitis Obliterans Syndrome

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

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.

Study Overview

• Status: Recruiting
• Conditions: Hematologic Malignancy; Bronchiolitis Obliterans Syndrome
• Intervention / Treatment: Drug: Ruxolitinib

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • The First Affiliated Hospital of Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: treatment group; Ruxolitinib twice daily treatment, combined with steroids 1mg/kg/day for two weeks, and tampering 0.25 mg/kg/day every week	Drug: Ruxolitinib; Oral ruxolitinib twice daily; Other Names: Ruxolitinib twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
Overall Survival	The proportion of patients survival at two years after enrollment of ruxolitinib treatment	2 years
cGVHD progression-free survival	Participants alive without cGVHD progression are censored at the date of last disease evaluation	2 years
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
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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 1, 2022
• Primary Completion (ANTICIPATED): June 1, 2024
• Study Completion (ANTICIPATED): January 1, 2025

Study Registration Dates

• First Submitted: June 7, 2022
• First Submitted That Met QC Criteria: June 7, 2022
• First Posted (ACTUAL): June 10, 2022

Study Record Updates

• Last Update Posted (ACTUAL): October 19, 2022
• Last Update Submitted That Met QC Criteria: October 18, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: bronchiolitis obliterans syndrome; chronic graft versus host disease; Allogeneic Hematopoietic stem cell transplantation
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Disease; Hematologic Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Bronchitis; Syndrome; Hematologic Neoplasms; Bronchiolitis; Bronchiolitis Obliterans
• Other Study ID Numbers: ZJU-HSCT-BOS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No