Itacitinib for the Treatment of Bronchiolitis Obliterans Syndrome After Donor Hematopoietic Cell Transplant
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
PRIMARY OBJECTIVE:
- To assess the safety of itacitinib in patients with bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic cell transplantation (HCT).
SECONDARY OBJECTIVES:
-
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.
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To assess change in the Lee chronic graft versus host disease (GVHD) symptom scale at 3 months and 6 months post-treatment.
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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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment (itacitinib) Patents receive itacitinib PO QD for up to 1 year in the absence of disease progression or unacceptable toxicity. |
Drug: Itacitinib
Given PO
Other Names:
Drug: Itacitinib Adipate
Given PO
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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 St. George's Respiratory Questionnaire (SGRQ 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. Participants will answer a St. George's Respiratory Questionnaire. (Very Poor, Poor, Fair, Good, Very Good)?
- Change in well-established patient reported outcomes used in chronic graft versus host disease (GVHD) studies [Baseline up to 6 months]
Will include the Lee chronic GVHD symptom scale Lee symptom scale. 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. The Lee Chronic GVHD Symptom Scale is a 30 item instrument with 7 subscales (skin, eyes, mouth, lung, nutrition, energy and psych) containing 2-7 items. Response options range from 0-4 (0-Not at all, 1-Slightly, 2-Moderately, 3-Quite a bit, 4-Extremely).
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
-
BOS diagnosed within the past 6 months of enrollment, defined by 2015 National Institutes of Health (NIH) Consensus Criteria
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Undergone allogeneic stem cell transplant (SCT)
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Absolute neutrophil count (ANC) > 1,000/microL
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Hemoglobin > 8 gm/dL (untransfused)
-
Platelet count > 25,000/microL (untransfused)
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Karnofsky performance score >= 60
-
The ability to understand and sign a written informed consent form
Exclusion Criteria:
-
Prior treatment with any other JAK inhibitor (including ruxolitinib) for BOS or any other indication within the past 6 months of enrollment
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Patients on mechanical ventilation or resting by pulse oximetry oxygen (O2) saturation < 88%
-
Forced expiratory volume in 1 second (FEV1) < 40% predicted
-
Relapsed primary malignancy for which SCT was performed
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History of progressive multifocal leuko-encephalopathy (PML)
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Active uncontrolled bacterial, fungal, parasitic, or viral infection
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Known human immunodeficiency virus (HIV) infection or active hepatitis B or C infections
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History of tuberculosis anytime after SCT
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Severe renal dysfunction defined by serum creatinine > 2 mg/dL, creatinine clearance < 60 mL/minute or dialysis dependence
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Serum transaminases > 5 x upper limit of normal
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Inability to perform pulmonary function test (PFT) reliably
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Positive beta human chorionic gonadotropin (HCG) test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization
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Life expectancy < 6 months
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Concurrent treatment with antiplatelet agents (aspirin, non-steroidal anti-inflammatory drug [NSAIDs] and related drugs) or anticoagulants (warfarin, heparin, oral anticoagulants - direct thrombin or anti Xa agents and related drugs)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | M D Anderson Cancer Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- M.D. Anderson Cancer Center
Investigators
- Principal Investigator: Rohtesh S Mehta, M.D. Anderson Cancer Center
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 2018-0489
- NCI-2019-08252
- 2018-0489