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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

About this trial

This is an interventional treatment trial for Hematopoietic Stem Cell Transplant (HSCT)

Eligibility Criteria

5 Years - 60 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

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

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

Sara.Loveless@cchmc.org

First Name & Middle Initial & Last Name or Official Title & Degree

Evelyn Nguyen, MS

Phone

(513) 636-4379

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

griffint@umn.edu

First Name & Middle Initial & Last Name & Degree

Amanda Simmons

Phone

612-626-4610

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

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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