A Phase II Study of Itacitinib in Patients With Steroid Refractory Immune Related Adverse Events Arising From Immune Checkpoint Inhibitors
概览
- 阶段
- 2 期
- 干预措施
- Corticosteroid
- 疾病 / 适应症
- Hematopoietic and Lymphoid Cell Neoplasm
- 发起方
- Douglas Johnson
- 入组人数
- 25
- 主要终点
- Incidence of immune related adverse events (irAE)
- 状态
- 撤回
- 最后更新
- 5天前
概览
简要总结
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.
详细描述
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.
研究者
Douglas Johnson
Associate Professor of Medicine
Vanderbilt-Ingram Cancer Center
入排标准
入选标准
- •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
排除标准
- •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 \<
- •(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).
研究组 & 干预措施
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.
干预措施: Corticosteroid
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.
干预措施: Endoscopic Procedure
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.
干预措施: Skin biopsy
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.
干预措施: Biospecimen Collection
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.
干预措施: Itacitinib
结局指标
主要结局
Incidence of immune related adverse events (irAE)
时间窗: Baseline up to 60 days post last dose of itacitinib
次要结局
- Progression-free survival(Baseline up to 60 days post last dose of itacitinib)
- Hospitalization presence(Days 14 and 28)
- Need for therapy escalation and absence of steroids(From start of itacitinib to 60 days after stopping itacitinib)
- The rate of improvement at earlier timepoints will be followed.(Baseline up to 60 days post last dose of itacitinib)
- Rate of irAEs(Baseline up to 60 days post last dose of itacitinib)
- Need for therapy escalation and presence of steroids(From start of itacitinib to 60 days after stopping itacitinib)
- The rate of delayed relapses will be followed.(Baseline up to 60 days post last dose of itacitinib)
- Objective response rate(Baseline up to 60 days post last dose of itacitinib)