Itacitinib for Low Risk GVHD

Study Overview
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Brief Summary
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Graft-versus-host disease (GVHD) is treated with high doses of systemic steroids which can lead to serious complications. A new blood test can identify patients whose GVHD is most likely to respond to well to treatment (low risk GVHD). This study will test whether patients with low risk GVHD can be successfully treated without steroids. Patients who participate with this study will be treated with itacitinib instead of steroids. Itacitinib is an experimental drug with an excellent safety record and appears to have activity as a GVHD treatment.

Detailed Description
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Patients with newly diagnosed low risk acute GVHD defined as Minnesota standard risk based on symptoms and Ann Arbor 1 GVHD based on biomarkers were eligible if they met all other eligible criteria (see eligibility criteria below). Enrolled patients were required to start treatment within 4 days of confirmation of Ann Arbor 1 status. Treatment consisted of itacitinib 200 mg daily for 28 days. Patients with a clinical response on day 28 were eligible for a second 28 day cycle of itacitinib 200 mg daily. Missed doses could be made up by extending the treatment duration for up to 2 additional weeks. Medications given for GVHD prophylaxis and topical treatments for GVHD were allowed. Supportive care was provided according to institutional standards. Itacitinib was permanently discontinued after any of the following: administration of 56 doses of itacitinib or initiation of systemic corticosteroids or any other systemic treatment for GVHD or patient withdrawal from the study or general or specific changes in the patient's condition render the patient unacceptable for further treatment in the judgment of the investigator OR ten weeks elapsed since the first dose of itacitinib.

Official Title
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Itacitinib Monotherapy for Low Risk Graft-vs-Host Disease

Conditions
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GVHD, Low Risk Acute Graft-versus-host Disease, Graft-versus-host-disease

Intervention / Treatment
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* Drug: Itacitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly diagnosed GVHD that meets criteria for Minnesota standard risk Ann Arbor 1 GVHD by biomarkers GVHD not previously treated systemically (topical therapies and non-absorbed steroids are allowed) Any donor type, HLA-match, conditioning regimen is acceptable Age 12 - 75 years (children <18 years must also weigh 50 kg or more) Patients must be engrafted post-transplant (ANC >500/μL and platelet count >20,000). Use of growth factor supplementation to maintain neutrophil count is allowed. Direct bilirubin must be <2 mg/dL unless the elevation is known to be due to Gilbert syndrome within 3 days prior to enrollment. ALT/SGPT and AST/SGOT must be <5x the upper limit of the normal range within 3 days prior to enrollment. Signed and dated written informed consent obtained from patient or legal representative. Exclusion Criteria: Patients currently being treated with any JAK inhibitor including ruxolitinib Relapsed, progressing, or persistent malignancy requiring withdrawal of systemic immune suppression Patients with uncontrolled infection (i.e., progressive symptoms related to infection despite treatment or persistently positive microbiological cultures despite treatment or any other evidence of severe sepsis) Severe organ dysfunction including requirement for dialysis, mechanical ventilation or oxygen supplementation exceeding 40% FiO2 within 7 days of enrollment. Creatinine clearance or estimated glomerular filtration rate <30 ml/min as calculated by institutional practice (e.g., Cockcroft-Gault equation, CKD-EPI equation, etc) A clinical presentation resembling de novo chronic GVHD or overlap syndrome developing before or present at the time of enrollment Patients receiving corticosteroids >10 mg/day prednisone (or other steroid equivalent) for any indication within 7 days before the onset of acute GVHD except for adrenal insufficiency or premedication for transfusions/IV meds Patients who are pregnant Patients receiving investigational agents within 30 days of enrollment. However, the Principal Investigator (PI) may approve prior use of an investigational agent if the agent is not expected to interfere with the safety or the efficacy of itacitinib History of allergic reaction to itacitinib or any JAK inhibitor

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open label, single arm, non-inferiority study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Itacitinib<br>Itacitinib 200 mg administered orally daily | Drug: Itacitinib<br>* for up to 56 days<br>* Other names: INCB389110;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Who Achieve CR or PR by Day 28 of Treatment | Number of patients who achieve CR or PR by day 28 of treatment with itacitinib without the addition of any other systemic GVHD treatment including steroids. Complete Response (CR): All evaluable organs (skin, liver, GI tract) stage 0. For a response to be scored as CR on day 28, the patient must be in CR on that day and have had no intervening additional GVHD therapy. Partial Response (PR): An improvement in one or more organ involved with GVHD symptoms without worsening in others. For a response to be scored as PR on day 28, the patient must be in PR on that day and have had no intervening additional GVHD therapy. | Day 28 | 
| Number of Participants Who Developed Steroid Refractory GVHD | Number of participants who developed steroid refractory GVHD within 28 days of starting steroids. Steroid-refractory GVHD (defined as GVHD that worsens (increase by one or more grade) after 3 days, or fails to respond to treatment within 7 days (for GVHD grade III) or 14 days (for GVHD grade II) or 2nd line therapy beyond systemic steroid treatment is begun within 28 days of starting steroids. | Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Serious Infectious | Number of participants who developed serious infections by day 90. Serious infectious complications is defined as any viral and bacterial infections requiring treatment and proven fungal infections. | Day 90 | 
| Number of Participants Alive at 6 Months and 1 Year | Number of overall survival (OS), defined as the duration from the date of diagnosis to death or last follow-up, with no restriction on the cause of death. | 6 months and 1 year | 
| Number of Participants With Non-relapse Mortality (NRM) | Number of participants with non-relapse mortality (NRM) at 6 months and 1 year | 6 months and 1 year | 
| Number of Participants Who Relapsed | Number of participants who relapsed by 6 months and by 1 year | 6 months and 1 year | 
| Number of Participants Who Developed Chronic GVHD | Number of participants who developed chronic GVHD requiring systemic treatment at 1 year | 1 year | 
| Cumulative Steroid Dose | Cumulative steroid dose (over 4 weeks) in patients who receive steroids as second line therapy | Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Graft-versus-host disease, Itacitinib