- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05660421
Itacitinib for the Treatment Steroid Refractory Immune Related Adverse Events Arising From Immune Checkpoint Inhibitors
A Phase II Study of Itacitinib in Patients With Steroid Refractory Immune Related Adverse Events Arising From Immune Checkpoint Inhibitors
Study Overview
Status
Detailed Description
PRIMARY OBJECTIVE:
I. To define the rate of improvement of steroid-refractory immune related adverse events (irAEs) in patients treated with ICI at 28 days.
SECONDARY OBJECTIVES:
I. To define whether anti-tumor activity is preserved (response rate, progression free survival [PFS], T cell populations and function in the tumor).
II. To assess freedom from hospitalization and any grade improvement at 14 and 28 days.
III. To assess rate of therapy escalation (increased dose of steroids, other immunosuppressant) by day 60 follow up.
IV. To define cancer-specific and toxicity-specific survival at 6 months. V. To define the rate of improvement of steroid-refractory irAEs in patients treated with ICI at any time, and at 60 days (defined as improvement to Common Terminology Criteria for Adverse Events [CTCAE] Grade 0-1).
VI. To define the proportion of patients able to be tapered off steroids at Day 29 and at Day 30 follow up.
VII. To define the safety of itacitinib in patients with steroid-refractory irAEs.
OUTLINE:
Patients receive itacitinib orally (PO) and corticosteroids PO or intravenously (IV) on study. Patients may undergo endoscopy and skin biopsy throughout the study. Patients also undergo blood collection throughout the study.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Vanderbilt-Ingram Services for Timely Access
- Phone Number: 800-811-8480
- Email: cip@vumc.org
Study Locations
-
-
Tennessee
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Nashville, Tennessee, United States, 37232
- Recruiting
- Vanderbilt University/Ingram Cancer Center
-
Contact:
- Vanderbilt-Ingram Service for Timely Access
- Phone Number: 800-811-8480
- Email: cip@vumc.org
-
Principal Investigator:
- Douglas Johnson, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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
Encephalitis
- Neurologic symptoms consistent with encephalitis
- Lumbar puncture and infectious disease consult to rule out infectious etiologies if clinical suspicion for infectious causes
Guillain Barre
- MRI performed to rule out spinal cord compression
- Neurology consult to confirm diagnosis (or extremely high suspicion)
Myasthenia Gravis
- MRI performed to rule out spinal cord compression and brain metastases
- Neurology consult to confirm diagnosis (or extremely high suspicion)
- Pericarditis
- Vasculitis
- Gastritis
Other toxicities
- Other steroid refractory toxicities not listed in the above list
- NOTE: Endocrine toxicities (including hypophysitis, hypopituitarism, hypothyroidism, thyrotoxicosis, immune checkpoint inhibitor-induced diabetes, and primary adrenal insufficiency) will NOT qualify for inclusion.
- Must have received oral or intravenous corticosteroids of at least 50mg per day prednisone equivalent dosing (approximately 1mg/kg daily) for ≥ 48 hours of therapy with worsening or lack of improvement to Grade 2.
- May have been treated with additional immunomodulators (one or more) prior to study entry (e.g. infliximab, mycophenolate mofetil, intravenous immunoglobulin), provided such immunomodulators are discontinued prior to first dose of study therapy.
Adequate organ and marrow function as defined below:
- White blood cell (WBC) ≥ 2.0 ×109/L.
- Neutrophil (ANC) ≥ 1.5 ×109/L.
- Platelet (PLT) ≥ 75 ×109/L.
- Hemoglobin (Hgb) ≥ 8.0 g/dL.
- AST and ALT ≤ 3 x ULN in subjects without hepatic metastases; AST and ALT ≤ 5 x ULN in subjects with hepatic metastases, if AST/ALTelevation is NOT due to ICI-induced hepatitis; (Exception (without or with hepatic metastases): no limit for patients with ICI-induced hepatitis).
- Total bilirubin ≤ 2 x ULN not due to ICI-hepatitis (except subjects with Gilbert syndrome, where total bilirubin must be < 3.0 mg/dL), (Exception: no limit for patients with ICI-induced hepatitis).
Reproductive status:
- Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to the start of study treatment.
- Women must not be breastfeeding.
- Women of childbearing potential must agree to follow instructions for method(s) of contraception for the duration of study drug treatment and 60 days after the last dose of study treatment or longer if required based on prior immunotherapy received (for example, at least 4-5 months for nivolumab and pembrolizumab).
- Males who are sexually active with Women of childbearing potential must agree to follow instructions for method(s) of contraception for the duration of study treatment and 60 days after the last dose of study drug or longer if required based on prior immunotherapy received.
- Azoospermic males are exempt from contraceptive requirements. WOCBP who are continuously not heterosexually active are also exempt from contraceptive requirements but still must undergo pregnancy testing as described in this section.
- Investigators shall counsel Women of childbearing potential, and male participants who are sexually active with Women of childbearing potential on the importance of pregnancy prevention and the implications of an unexpected pregnancy. Investigators shall advise on the use of highly effective methods of contraception which have a failure rate of < 1% when used consistently and correctly. Women of childbearing potential and men must agree to use adequate contraception (for example, hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of protocol treatment.
Exclusion Criteria:
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (itacitinib)
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.
|
Given by mouth
Given by mouth or by vein
Undergo endoscopic procedure
Undergo skin biopsy
Undergo collection of blood and stool
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Incidence of immune related adverse events (irAE)
Time Frame: Baseline up to 60 days post last dose of itacitinib
|
Baseline up to 60 days post last dose of itacitinib
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective response rate
Time Frame: Baseline up to 60 days post last dose of itacitinib
|
Will be measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as best response reported by the investigator at scans subsequent to itacitinib therapy and will be obtained descriptively by chart review.
|
Baseline up to 60 days post last dose of itacitinib
|
Progression-free survival
Time Frame: Baseline up to 60 days post last dose of itacitinib
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Will be obtained using RECIST 1.1 and obtained descriptively by chart review.
|
Baseline up to 60 days post last dose of itacitinib
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Hospitalization presence
Time Frame: Days 14 and 28
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Need for hospitalization will be recorded.
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Days 14 and 28
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Need for therapy escalation and presence of steroids
Time Frame: From start of itacitinib to 60 days after stopping itacitinib
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The presence of additional immunosuppression added after starting itacitinib or escalation of steroid dose will be recorded.
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From start of itacitinib to 60 days after stopping itacitinib
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Need for therapy escalation and absence of steroids
Time Frame: From start of itacitinib to 60 days after stopping itacitinib
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The absence of additional immunosuppression added after starting itacitinib or escalation of steroid dose will be recorded.
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From start of itacitinib to 60 days after stopping itacitinib
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The rate of delayed relapses will be followed.
Time Frame: Baseline up to 60 days post last dose of itacitinib
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Rate of irAEs
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Baseline up to 60 days post last dose of itacitinib
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The rate of improvement at earlier timepoints will be followed.
Time Frame: Baseline up to 60 days post last dose of itacitinib
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Rate of irAEs
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Baseline up to 60 days post last dose of itacitinib
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Rate of irAEs
Time Frame: Baseline up to 60 days post last dose of itacitinib
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The rate of ability to resume ICI (in select patients, per study investigator decision) will be followed.
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Baseline up to 60 days post last dose of itacitinib
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Douglas Johnson, MD, Vanderbilt University/Ingram Cancer Center
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- VICCCTT2193
- NCI-2022-09649 (Registry Identifier: NCI, Clinical Trials Reporting Program)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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