Clinical trial NCT03846479: Itacitinib for Low Risk GVHD
Official title: Itacitinib Monotherapy for Low Risk Graft-vs-Host Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Low Risk Acute Graft-versus-host Disease
Graft-versus-host-disease
GVHD
Keywords: Graft-versus-host disease
Itacitinib
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
First posted: 2019-02-19
Enrollment: 70
Sex: ALL
Minimum age (years): 12
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open label, single arm, non-inferiority study
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Patients Who Achieve CR or PR by Day 28 of Treatment
timeFrame: Day 28
measure: Number of Participants Who Developed Steroid Refractory GVHD
timeFrame: Day 28
Secondary outcomes:
measure: Number of Participants With Serious Infectious
timeFrame: Day 90
measure: Number of Participants Alive at 6 Months and 1 Year
timeFrame: 6 months and 1 year
measure: Number of Participants With Non-relapse Mortality (NRM)
timeFrame: 6 months and 1 year
measure: Number of Participants Who Relapsed
timeFrame: 6 months and 1 year
measure: Number of Participants Who Developed Chronic GVHD
timeFrame: 1 year
measure: Cumulative Steroid Dose
timeFrame: Day 28
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles
state: California
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta
state: Georgia
city: Fairway
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: The Mount Sinai Hospital
state: New York
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania, Abramson Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: John Levine, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: