Itacitinib for Low Risk GVHD

NCT ID: NCT03846479

Last Updated: 2023-02-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-25
• Study Completion Date: 2022-05-11

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.

Conditions

Low Risk Acute Graft-versus-host Disease; Graft-versus-host-disease; GVHD

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Itacitinib

Itacitinib 200 mg administered orally daily

Group Type: EXPERIMENTAL

Itacitinib

Intervention Type: DRUG

for up to 56 days

Interventions

Itacitinib

for up to 56 days

Intervention Type: DRUG

Other Intervention Names

INCB389110

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

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

John Levine

OTHER

Sponsor Role: lead

Responsible Party

John Levine

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

John Levine, MD, MS

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Locations

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Children's Hospital of Los Angeles

Los Angeles, California, United States

Emory University

Atlanta, Georgia, United States

Children's Healthcare of Atlanta

Atlanta, Georgia, United States

University of Kansas Cancer Center

Fairway, Kansas, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Mayo Clinic

Rochester, Minnesota, United States

The Mount Sinai Hospital

New York, New York, United States

Ohio State University

Columbus, Ohio, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

University of Pennsylvania, Abramson Cancer Center

Philadelphia, Pennsylvania, United States

Vanderbilt University

Nashville, Tennessee, United States

MD Anderson Cancer Center

Houston, Texas, United States

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Countries

United States

References

Etra A, Capellini A, Alousi A, Al Malki MM, Choe H, DeFilipp Z, Hogan WJ, Kitko CL, Ayuk F, Baez J, Gandhi I, Kasikis S, Gleich S, Hexner E, Hoepting M, Kapoor U, Kowalyk S, Kwon D, Langston A, Mielcarek M, Morales G, Ozbek U, Qayed M, Reshef R, Rosler W, Spyrou N, Young R, Chen YB, Ferrara JLM, Levine JE. Effective treatment of low-risk acute GVHD with itacitinib monotherapy. Blood. 2023 Feb 2;141(5):481-489. doi: 10.1182/blood.2022017442.

Reference Type: DERIVED

PMID: 36095841 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

GCO 18-1684

Identifier Type: -

Identifier Source: org_study_id