Itacitinib for the Treatment Steroid Refractory Immune Related Adverse Events Arising From Immune Checkpoint Inhibitors

NCT05660421 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: VICCCTT2193NCI-2022-09649
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase II trial tests how well itacitinib works in in patients with immune related adverse events (irAEs) arising from immune checkpoint inhibitors (ICI) that do not respond to steroids (steroid refractory). Steroids are the usual treatment for these side effects. However, sometimes steroids do not improve or fix the side effects. Giving itacitinib may be effective in treating patients with known or suspected problems coming from ICIs, that do not resolve or improve with steroids, by reducing the patients immune system response that can cause the irAEs.

Conditions

Hematopoietic and Lymphoid Cell Neoplasm; Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (1)

• Incidence of immune related adverse events (irAE)

  Baseline up to 60 days post last dose of itacitinib

Secondary Outcomes (8)

• Objective response rate

  Baseline up to 60 days post last dose of itacitinib

• Progression-free survival

  Baseline up to 60 days post last dose of itacitinib

• Hospitalization presence

  Days 14 and 28

• Need for therapy escalation and presence of steroids

  From start of itacitinib to 60 days after stopping itacitinib

• Need for therapy escalation and absence of steroids

  From start of itacitinib to 60 days after stopping itacitinib

Study Arms (1)

Treatment (itacitinib)

EXPERIMENTAL

Patients receive itacitinib PO and corticosteroids PO or IV. Patients may undergo endoscopy and skin biopsy throughout the study. Patients also undergo blood collection throughout the study.

Drug: Itacitinib; Drug: Corticosteroid; Procedure: Endoscopic Procedure; Procedure: Skin biopsy; Procedure: Biospecimen Collection

Interventions

Itacitinib DRUG

Given by mouth

Treatment (itacitinib)

Corticosteroid DRUG

Given by mouth or by vein

Treatment (itacitinib)

Endoscopic Procedure PROCEDURE

Undergo endoscopic procedure

Treatment (itacitinib)

Skin biopsy PROCEDURE

Undergo skin biopsy

Treatment (itacitinib)

Biospecimen Collection PROCEDURE

Undergo collection of blood and stool

Treatment (itacitinib)

Eligibility Criteria

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

You may qualify if:

• Must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal participant care.
• Must be willing and able to comply with scheduled visits, treatment schedule,laboratory tests, biopsies, and other requirements of the study.
• Must have received at least one immune checkpoint inhibitor (ICI) therapy either as single agent(s) or in combination(s), including but not limited to nivolumab, ipilimumab, pembrolizumab, cemiplimab, atezolizumab, durvalumab, or avelumab.
• Must experience at least one Grade 2, 3 or 4 (CTCAE Version 5.0) toxicity/immune-related adverse event (irAE) attributed to immune checkpoint inhibitor (ICI) therapy as diagnosed by the patient's study physician. This may be established by clinical, histological, or imaging criteria as defined below:
• Symptoms must be attributed to an immune-related adverse event (irAE), with no infectious or alternative cause suspected by the patient's study physician.
• Must be actively experiencing Grade 2+ irAE (at the time of screening) as broadly defined below:
• Cutaneous toxicity (including skin rash)
• Colitis/enteritis (As defined by Grade 2+ diarrhea or Grade 2+ colitis (either or both conditions)
• Pneumonitis
• Arthritis
• Hepatitis (As defined by Grade 2+ elevation in AST or ALT (either or both values elevated)
• Nephritis (As defined by either Grade 2+ elevation in creatinine and/or proteinuria of at least 2+ on urinalysis attributed to ICI)
• Myocarditis (Given the vague nature of symptomatic myocarditis grading, troponin levels will be primarily used to grade myocarditis,( Troponin \>2ng/ml), (Presumed diagnosis of myocarditis (myocardial infarction ruled out clinically)
• Myositis (Defined as grade 2 myositis symptoms per CTCAE OR grade 2 elevations in creatinine kinase levels)
• Neurologic toxicity

You may not qualify if:

• Toxicity deemed by patient's study physician to be primarily caused by another etiology (bacterial infection, other anticancer agents, etc.).
• Ongoing serious infection requiring IV antibiotics.
• Prior treatment with a JAK inhibitor within the past 8 weeks before first dose of protocol indicated treatment.
• Known HIV infection with CD4 count \< 200. (Testing not required by this study.)
• History or current diagnosis of cardiac disease indicating significant risk of safety for participation in the study, such as uncontrolled or significant cardiac disease, including any of the following:
• Recent myocardial infarction (within 6 months before first dose of protocol indicated treatment).
• New York Heart Association Class III or IV congestive heart failure.
• Unstable angina (within last 6 months before first dose of protocol-indicated treatment).
• Clinically significant (symptomatic) cardiac arrhythmias per judgment of patient's study physician (e.g., sustained ventricular tachycardia, and clinically significant second or third degree AV block without a pacemaker).
• Uncontrolled hypertension defined as blood pressure persistently above 160 systolic or 100 diastolic despite antihypertensive therapy.
• Known allergies, hypersensitivity, or intolerance to any study medications or excipients.
• History of solid organ transplant or allogeneic stem cell transplant with active graft versus host disease.
• Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug/treatment and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data

Sponsors & Collaborators

• Douglas Johnson: lead
• Incyte Corporation: collaborator

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

itacitinib; Adrenal Cortex Hormones; Endoscopy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Diagnostic Techniques, Surgical; Diagnostic Techniques and Procedures; Diagnosis; Minimally Invasive Surgical Procedures; Surgical Procedures, Operative

Study Officials

• Douglas Johnson, MD

  Vanderbilt University/Ingram Cancer Center

  PRINCIPAL INVESTIGATOR

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: Associate Professor of Medicine

Study Record Dates

• First Submitted: November 30, 2022
• First Posted: December 21, 2022
• Study Start: March 3, 2023
• Primary Completion: April 3, 2025
• Study Completion: April 3, 2025
• Last Updated: April 27, 2026

Record last verified: 2026-04