Itacitinib for the Treatment of Bronchiolitis Obliterans Syndrome After Donor Hematopoietic Cell Transplant

Phase 1

Active, not recruiting

• Conditions: Bronchiolitis Obliterans
• Interventions: Drug: Itacitinib; Drug: Itacitinib Adipate

• Registration Number: NCT04239989
• Lead Sponsor: M.D. Anderson Cancer Center

Brief Summary

This phase I trial studies how well itacitinib works for the treatment of bronchiolitis obliterans syndrome after donor hematopoietic cell transplant. Itacitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Description

PRIMARY OBJECTIVE:

I. To assess the safety of itacitinib in patients with bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic cell transplantation (HCT).

SECONDARY OBJECTIVES:

I. To assess treatment failure at 3 months and 6 months.

II. To assess change in symptom-based lung score at 3 months and 6 months.

III. To assess change in the St. George Respiratory Questionnaire and Study Short Form 36 at 3 months and 6 months.

IV. To assess change in the Lee chronic graft versus host disease (GVHD) symptom scale at 3 months and 6 months post-treatment.

V. To assess change in 6-minute walk test at 3 months and 6 months.

VI. To assess failure-free survival at 6 months.

VII. To assess non-relapse mortality at 6 months.

VIII. To assess overall survival at 6 months.

OUTLINE:

Patents receive itacitinib orally (PO) once daily (QD) for up to 1 year in the absence of disease progression or unacceptable toxicity.

Study Timeline

• Study First Submitted: 2019-12-30
• Study First Submitted QC: 2020-01-21
• Study First Posted: 2020-01-27
• Study Start: 2021-10-08
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-24
• Last Update Posted: 2025-04-27
• Primary Completion: 2025-05-31
• Study Completion: 2025-05-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 8

Inclusion Criteria

Not provided

Exclusion Criteria

1. Prior treatment with any other JAK inhibitor (including Ruxolitinib) for BOS or any other indication within the past 6 months of enrolment.
2. Patients on mechanical ventilation or resting by pulse oximetry O2 saturation <88%
3. FEV1 <40% predicted
4. Relapsed primary malignancy for which SCT was performed
5. History of progressive multifocal leuko-encephalopathy (PML)
6. Active uncontrolled bacterial, fungal, parasitic, or viral infection
7. Known human immunodeficiency virus (HIV) infection or active hepatitis B or C infections.
8. History of tuberculosis anytime after SCT
9. Severe renal dysfunction defined by serum creatinine > 2 mg/dL, creatinine clearance <60 mL/minute or dialysis dependence
10. Serum transaminases > 5 × upper limit of normal
11. inability to perform PFT reliably
12. Positive Beta HCG test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization.
13. Lactating/nursing women
14. Life expectancy < 6 months
15. Other severe organ dysfunction unrelated to underlying GVHD. For example, uncontrolled or significant cardiac disease, including any of the following: recent myocardial infarction (within last 6 months from randomization); New York Heart Association Class III or IV congestive heart failure; unstable angina (within last 6 months prior to randomization); clinically significant (symptomatic) cardiac arrhythmias (e.g., sustained ventricular; tachycardia, and clinically significant second or third degree AV block without a pacemaker); uncontrolled hypertension. Or any other concurrent severe and/or uncontrolled medical conditions which, in the opinion of the investigator, could compromise participation in the study, pose a significant risk to the subject, or interfere with study results.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (itacitinib)	Itacitinib	Patents receive itacitinib PO QD for up to 1 year in the absence of disease progression or unacceptable toxicity.
Treatment (itacitinib)	Itacitinib Adipate	Patents receive itacitinib PO QD for up to 1 year in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Monitoring the Dose Limiting Toxicities (DLT) of administering Itacitinib	Up to 6 months	Number of participants who develop DLT's after the administration of the study drug

Secondary Outcome Measures

Name	Time	Method
Treatment failure	At 3 and 6 months	Defined as a decrease in the absolute value of % forced expiratory volume in 1 second (FEV1) by 10% or more.
Changes in National Institutes of Health (NIH) symptom-based lung score	At 3 and 6 months	Improvement in NIH symptom-based lung score; Score 0 (no symptoms), Score 1 (shortness of breath with stairs), Score 2 (shortness of breath on flat ground), and Score 3 (shortness of breath at rest or requiring oxygen
Change in well-established patient reported outcomes used in chronic graft versus host disease (GVHD) studies	Baseline and at 3 and 6 months	Will include the study Short Form 36 (SF-36), NIH lung symptom score and SF-36 due to the longitudinal nature of the observations. Regression models will include time, and different covariance structures will be included, including unstructured and autoregressive integrated moving average (ARIMA). The analysis will be adjusted for potential confounding variables.
Change in 6-minute walk test	Baseline and at 3 and 6 months
Failure-free survival	At 6 months	Will be assessed and monitored
Non-relapse mortality	At 6 months	Defined as the absence of need for additional line treatment, non-relapse mortality and recurrent malignancy.
Overall survival	At 6 months	Will be assessed and monitored

Trial Locations

Locations (1)

M D Anderson Cancer Center; 🇺🇸 Houston, Texas, United States