Itacitinib for Low Risk GVHD

NCT03846479 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: GCO 18-1684
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 14

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.

Conditions

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

Keywords

Graft-versus-host disease; Itacitinib

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (6)

• Number of Participants With Serious Infectious

  Day 90

• Number of Participants Alive at 6 Months and 1 Year

  6 months and 1 year

• Number of Participants With Non-relapse Mortality (NRM)

  6 months and 1 year

• Number of Participants Who Relapsed

  6 months and 1 year

• Number of Participants Who Developed Chronic GVHD

  1 year

Study Arms (1)

Itacitinib

EXPERIMENTAL

Itacitinib 200 mg administered orally daily

Drug: Itacitinib

Interventions

Itacitinib DRUG

for up to 56 days

Also known as: INCB389110

Itacitinib

Eligibility Criteria

• Age: 12 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• John Levine: lead

Study Sites (14)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

Children's Hospital of Los Angeles

Los Angeles, California, 90027, United States

Location

Emory University

Atlanta, Georgia, 30003, United States

Location

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

University of Kansas Cancer Center

Fairway, Kansas, 66205, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

The Mount Sinai Hospital

New York, New York, 10029, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pennsylvania, Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• 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.

  PMID: 36095841 DERIVED

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

itacitinib

Condition Hierarchy (Ancestors)

Immune System Diseases

Results Point of Contact

• Title: Dr. John Levine
• Organization: Icahn School of Medicine at Mount Sinai

john.levine@mssm.edu

212-241-6021

Study Officials

• John Levine, MD, MS

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: Open label, single arm, non-inferiority study

Study Record Dates

• First Submitted: February 17, 2019
• First Posted: February 19, 2019
• Study Start: March 25, 2019
• Primary Completion: May 7, 2021
• Study Completion: May 11, 2022
• Last Updated: February 6, 2023
• Results First Posted: February 6, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (14)