Clinical trial NCT04239989: Itacitinib for the Treatment of Bronchiolitis Obliterans Syndrome After Donor Hematopoietic Cell Transplant
Official title: A Phase I Study to Assess Safety of Selective JAK 1 Inhibitor, Itacitinib, in Patients With Bronchiolitis Obliterans Syndrome (BOS) After Allogeneic Hematopoietic Cell Transplant (HCT)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Bronchiolitis Obliterans
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
First posted: 2020-01-27
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion criteria:

1. BOS diagnosed within the past 6 months of enrollment, defined by 2015 National Institutes of Health (NIH) Consensus Criteria 126
2. Age 18-75 years
3. Undergone allogeneic SCT
4. ANC \>1,000/µL, hemoglobin \> 8 gm/dL (untransfused) and platelet count \>25,000/ µL (untransfused)
5. Karnofsky performance score \>60
6. The ability to understand and sign a written informed consent form
7. Contraception for women and men of child bearing potential. Permitted methods should be at least 99% effective in preventing pregnancy.
8. Male patients must be willing to refrain from donating sperm during their participation in the study and for at least 3 months after completing the study.

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.

Primary outcomes:
measure: Monitoring the Dose Limiting Toxicities (DLT) of administering Itacitinib
timeFrame: Up to 6 months
Secondary outcomes:
measure: Treatment failure
timeFrame: At 3 and 6 months
measure: Changes in National Institutes of Health (NIH) symptom-based lung score
timeFrame: At 3 and 6 months
measure: Change in well-established patient reported outcomes used in chronic graft versus host disease (GVHD) studies
timeFrame: Baseline and at 3 and 6 months
measure: Change in well-established patient reported outcomes used in chronic graft versus host disease (GVHD) studies
timeFrame: Baseline up to 6 months
measure: Change in well-established patient reported outcomes used in chronic graft versus host disease (GVHD) studies
timeFrame: Baseline and at 3 and 6 months
measure: Change in 6-minute walk test
timeFrame: Baseline and at 3 and 6 months
measure: Failure-free survival
timeFrame: At 6 months
measure: Non-relapse mortality
timeFrame: At 6 months
measure: Overall survival
timeFrame: At 6 months
Other outcomes:
Locations:
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Amin Alousi, MD
role: PRINCIPAL_INVESTIGATOR
References: