Back to resultsItacitinib for Low Risk GVHD
Primary Purpose
Low Risk Acute Graft-versus-host Disease, Graft-versus-host-disease, GVHD
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Itacitinib
Sponsored by
About this trial
This is an interventional treatment trial for Low Risk Acute Graft-versus-host Disease focused on measuring Graft-versus-host disease, Itacitinib
Eligibility Criteria
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
Sites / Locations
- City of Hope Comprehensive Cancer Center
- Children's Hospital of Los Angeles
- Emory University
- Children's Healthcare of Atlanta
- University of Kansas Cancer Center
- Massachusetts General Hospital
- Mayo Clinic
- The Mount Sinai Hospital
- Ohio State University
- Children's Hospital of Philadelphia
- University of Pennsylvania, Abramson Cancer Center
- Vanderbilt University
- MD Anderson Cancer Center
- Fred Hutchinson Cancer Research Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Itacitinib
Arm Description
Itacitinib 200 mg administered orally daily
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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.
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.
Number of Participants With Non-relapse Mortality (NRM)
Number of participants with non-relapse mortality (NRM) at 6 months and 1 year
Number of Participants Who Relapsed
Number of participants who relapsed by 6 months and by 1 year
Number of Participants Who Developed Chronic GVHD
Number of participants who developed chronic GVHD requiring systemic treatment at 1 year
Cumulative Steroid Dose
Cumulative steroid dose (over 4 weeks) in patients who receive steroids as second line therapy
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03846479
Brief Title
Itacitinib for Low Risk GVHD
Official Title
Itacitinib Monotherapy for Low Risk Graft-vs-Host Disease
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Completed
Study Start Date
March 25, 2019 (Actual)
Primary Completion Date
May 7, 2021 (Actual)
Study Completion Date
May 11, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
John Levine
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Low Risk Acute Graft-versus-host Disease, Graft-versus-host-disease, GVHD
Keywords
Graft-versus-host disease, Itacitinib
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Open label, single arm, non-inferiority study
Masking
None (Open Label)
Allocation
N/A
Enrollment
70 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Itacitinib
Arm Type
Experimental
Arm Description
Itacitinib 200 mg administered orally daily
Intervention Type
Drug
Intervention Name(s)
Itacitinib
Other Intervention Name(s)
INCB389110
Intervention Description
for up to 56 days
Primary Outcome Measure Information:
Title
Number of Patients Who Achieve CR or PR by Day 28 of Treatment
Description
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.
Time Frame
Day 28
Title
Number of Participants Who Developed Steroid Refractory GVHD
Description
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.
Time Frame
Day 28
Secondary Outcome Measure Information:
Title
Number of Participants With Serious Infectious
Description
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.
Time Frame
Day 90
Title
Number of Participants Alive at 6 Months and 1 Year
Description
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.
Time Frame
6 months and 1 year
Title
Number of Participants With Non-relapse Mortality (NRM)
Description
Number of participants with non-relapse mortality (NRM) at 6 months and 1 year
Time Frame
6 months and 1 year
Title
Number of Participants Who Relapsed
Description
Number of participants who relapsed by 6 months and by 1 year
Time Frame
6 months and 1 year
Title
Number of Participants Who Developed Chronic GVHD
Description
Number of participants who developed chronic GVHD requiring systemic treatment at 1 year
Time Frame
1 year
Title
Cumulative Steroid Dose
Description
Cumulative steroid dose (over 4 weeks) in patients who receive steroids as second line therapy
Time Frame
Day 28
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John Levine, MD, MS
Organizational Affiliation
Icahn School of Medicine at Mount Sinai
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope Comprehensive Cancer Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
Children's Hospital of Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30003
Country
United States
Facility Name
Children's Healthcare of Atlanta
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
University of Kansas Cancer Center
City
Fairway
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
The Mount Sinai Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
University of Pennsylvania, Abramson Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Vanderbilt University
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Fred Hutchinson Cancer Research Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Itacitinib for Low Risk GVHD
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