Ruxolitinib for Early Lung Dysfunction After Hematopoietic Stem Cell Transplant (HSCT)
Primary Purpose
Hematopoietic Stem Cell Transplant (HSCT), Bronchiolitis Obliterans (BO)
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ruxolitinib
Sponsored by
About this trial
This is an interventional treatment trial for Hematopoietic Stem Cell Transplant (HSCT)
Eligibility Criteria
Inclusion Criteria:
Subjects ≥ 5 years and ≤ 25 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 IOS
- 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.
Sites / Locations
- University of MinnesotaRecruiting
- Cincinnati Children's Hospital Medical CenterRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Ruxolitinib Treatment
Arm Description
Outcomes
Primary Outcome Measures
Number of participants with ruxolitinib treatment response
Treatment response is defined by stable and/or improved lung function as defined by the National Institutes of Health Chronic GVHD Response Criteria Working Group.
Secondary Outcome Measures
Percentage of participants with JAK inhibition
The presence of JAK inhibition will be measured by phospho stat5
Number of participants with lung function response measured by a Xenon MRI scan
The presence of a lung function response will be measured by a Xenon MRI scan
Number of participants with lung function response measured by oscillometry
The presence of a lung function response will be measured by oscillometry
Number of participants with lung function response measured by home spirometry
The presence of a lung function response will be measured by home spirometry
Full Information
NCT ID
NCT04908735
First Posted
May 26, 2021
Last Updated
July 10, 2023
Sponsor
Children's Hospital Medical Center, Cincinnati
1. Study Identification
Unique Protocol Identification Number
NCT04908735
Brief Title
Ruxolitinib for Early Lung Dysfunction After Hematopoietic Stem Cell Transplant
Acronym
HSCT
Official Title
Ruxolitinib for Early Lung Dysfunction After HSCT: a Phase II Study
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 12, 2021 (Actual)
Primary Completion Date
November 2025 (Anticipated)
Study Completion Date
November 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Hospital Medical Center, Cincinnati
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematopoietic Stem Cell Transplant (HSCT), Bronchiolitis Obliterans (BO)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Ruxolitinib Treatment
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Ruxolitinib
Intervention Description
Participants will receive ruxolitinib orally twice daily for 24 weeks.
Primary Outcome Measure Information:
Title
Number of participants with ruxolitinib treatment response
Description
Treatment response is defined by stable and/or improved lung function as defined by the National Institutes of Health Chronic GVHD Response Criteria Working Group.
Time Frame
6 months from early lung dysfunction diagnosis
Secondary Outcome Measure Information:
Title
Percentage of participants with JAK inhibition
Description
The presence of JAK inhibition will be measured by phospho stat5
Time Frame
24 weeks after ruxolitinib initiation
Title
Number of participants with lung function response measured by a Xenon MRI scan
Description
The presence of a lung function response will be measured by a Xenon MRI scan
Time Frame
24 weeks after ruxolitinib initiation
Title
Number of participants with lung function response measured by oscillometry
Description
The presence of a lung function response will be measured by oscillometry
Time Frame
24 weeks after ruxolitinib initiation
Title
Number of participants with lung function response measured by home spirometry
Description
The presence of a lung function response will be measured by home spirometry
Time Frame
24 weeks after ruxolitinib initiation
10. Eligibility
Sex
All
Minimum Age & Unit of Time
5 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sara Loveless, BSN, RN
Phone
(513) 803-7656
Email
Sara.Loveless@cchmc.org
First Name & Middle Initial & Last Name or Official Title & Degree
Evelyn Nguyen, MS
Phone
(513) 636-4379
Email
Evelyn.Nguyen@cchmc.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kasiani Myers, MD
Organizational Affiliation
Children's Hospital Medical Center, Cincinnati
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tamara Griffin
Phone
612-301-0164
Email
griffint@umn.edu
First Name & Middle Initial & Last Name & Degree
Amanda Simmons
Phone
612-626-4610
Email
simmo743@umn.edu
First Name & Middle Initial & Last Name & Degree
Samuel Goldfarb, MD
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sara Loveless, BSN, RN
Phone
513-803-7656
Email
Sara.Loveless@cchmc.org
First Name & Middle Initial & Last Name & Degree
Kasiani Myers, MD
12. IPD Sharing Statement
Learn more about this trial
Ruxolitinib for Early Lung Dysfunction After Hematopoietic Stem Cell Transplant
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