Optimizing Immunosuppression for Steroid-Refractory Anti-PD-1/PD-L1 Pneumonitis
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 1
- 试验地点
- 18
- 主要终点
- Pneumonitis Response Rate
研究概览
简要总结
This phase II trial studies how well infliximab and intravenous immunoglobulin therapy work in treating patients with pneumonitis that does not respond to steroid treatment. Immunotherapy with monoclonal antibodies such as, infliximab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Intravenous immunoglobulin therapy may improve pneumonitis. It is not yet known whether giving infliximab and intravenous immunoglobulin therapy will work better in treating patients with pneumonitis.
详细描述
PRIMARY OBJECTIVE:
I. To assess pneumonitis response to additional immunosuppression (infliximab or intravenous immunoglobulin therapy [IVIG]) in patients with steroid-refractory pneumonitis at 28-days.
SECONDARY OBJECTIVES:
I. To assess functional parameters of steroid-refractory pneumonitis at day 1, 14-days and 28-days after day 1 of receipt of additional immunosuppression (infliximab or IVIG).
II. To assess radiologic parameters of steroid-refractory pneumonitis at day 1, 14-days and 28-days after day 1 of receipt of additional immunosuppression (infliximab or IVIG).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must be English-speaking and be able to provide informed consent
- •Patient must be willing and able to undergo arterial blood gas assessment as per the treating investigator. Patient must not have contraindication for arterial blood gas assessment
- •Women must not be pregnant or breast-feeding due to the potential risk to the fetus of infliximab or IVIG. All females of childbearing potential must have a blood test or urine test within 14 days prior to randomization to rule out pregnancy. A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
- •Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method(s) of contraception or to abstain from sexual intercourse for a minimum of 56 days (the duration of their participation in the study)
- •Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-3
- •Patient may have received any number of lines of prior systemic therapy
- •Patient may have any solid tumor or hematologic malignancy is eligible
- •Patient must have received treatment with an anti-PD-1/PD-L1 agent either alone or in combination with another anti-cancer agent, as their most recent therapy prior to development of pneumonitis
- •Patient must have steroid-refractory pneumonitis defined as:
- •Grade 2 pneumonitis that has not clinically improved by a Common Terminology Criteria for Adverse Events (CTCAE) grade in greater than 72 hours or maximum of 14 days or
- •Grade 3 or higher pneumonitis that has not clinically improved by a CTCAE grade in greater than 48 hours or maximum of 14 days with high dose corticosteroids (methylprednisolone or prednisone 1-4 mg/kg/equivalent) as their most recent treatment for pneumonitis, as determined by the treating investigator
- •Patient may have received anti-PD-1/PD-L1 therapy as standard-of-care or part of a clinical trial
- •Patient must have had pathogen-negative infectious diagnostic evaluation within 14 days prior to randomization, and at a minimum these should include: blood culture, urine culture, sputum culture, and viral panel: rapid flu, respiratory syncytial virus (RSV), herpes simplex virus (HSV). Empiric antibiotics for culture negative infections are not an exclusion for study entry
- •Patient must have had a pathogen-negative bronchoscopic assessment of BAL fluid within 14 days prior to randomization. A minimum assessment for pathogens on BAL must include: gram stain, fungal panel, viral panel
- •Patient must have a negative tuberculosis assessment (TB spot test, quantiferon gold or tuberculin skin test) within 14 days prior to randomization
- •Patient must have chest computed tomography (CT) scan without contrast performed =< 14 days before randomization. Patient must not have a contraindication for CT
排除标准
- •Patient must not have clinical evidence of cardiac dysfunction (as determined by the treating investigator) as an alternative diagnosis to steroid-refractory pneumonitis
- •Patient must not be receiving anti-PD-1/-PD-L1 agent in combination with any of the following anti-cancer agents: docetaxel, cyclophosphamide, gefitinib, erlotinib, osimertinib, crizotinib, bleomycin, afatinib
- •Patient must not be receiving concurrent radiation therapy to the chest
- •Patient must not be deemed to have radiation pneumonitis. Patients with a history of stable radiation pneumonitis not requiring corticosteroid therapy within the last 3 months prior to randomization will be allowed on study
- •Patient must not have pre-existing interstitial lung disease or pneumonitis requiring corticosteroid therapy from any other cause, as determined by the treating investigator
- •Patient must not have an absolute contraindication to IVIG or infliximab, including: clinical history of severe hypersensitivity reaction, selective IgA deficiency, active hepatitis B, active tuberculosis, active human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) where a study subject has a CD4 count of =< 200 at screening, or drug interaction
研究组 & 干预措施
Arm A (infliximab)
Patients receive infliximab IV on day 1 followed by prednisone taper IV or PO for 4-6 weeks in the absence of disease progression or unacceptable toxicity. Patients may receive an additional dose of infliximab IV on day 14 at the discretion of the treating physician.
干预措施: Infliximab (Biological)
Arm B (intravenous immunoglobulin therapy)
Patients receive intravenous immunoglobulin therapy IV over 2-5 days per institutional guidelines followed by prednisone taper IV or PO for 4-6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Intravenous Immunoglobulin Therapy (Biological)
Arm A (infliximab)
Patients receive infliximab IV on day 1 followed by prednisone taper IV or PO for 4-6 weeks in the absence of disease progression or unacceptable toxicity. Patients may receive an additional dose of infliximab IV on day 14 at the discretion of the treating physician.
干预措施: Prednisone (Drug)
Arm B (intravenous immunoglobulin therapy)
Patients receive intravenous immunoglobulin therapy IV over 2-5 days per institutional guidelines followed by prednisone taper IV or PO for 4-6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Prednisone (Drug)
Arm A (infliximab)
Patients receive infliximab IV on day 1 followed by prednisone taper IV or PO for 4-6 weeks in the absence of disease progression or unacceptable toxicity. Patients may receive an additional dose of infliximab IV on day 14 at the discretion of the treating physician.
干预措施: Methylprednisolone (Drug)
Arm B (intravenous immunoglobulin therapy)
Patients receive intravenous immunoglobulin therapy IV over 2-5 days per institutional guidelines followed by prednisone taper IV or PO for 4-6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Methylprednisolone (Drug)
结局指标
主要结局
Pneumonitis Response Rate
时间窗: At day 28
Pneumonitis response will be defined as an improvement in partial pressure of arterial oxygen (PaO2)/fraction of inspired oxygen (FiO2) of \>= 20% measured by PaO2 and recording of the FiO2 received by the patient at the time of the arterial blood gas assessment, on day 28 compared with day 1.
次要结局
- Number of Deaths Within 28 Days(Up to 28 days)
- Proportion of Patients With Radiologic Response for Steroid-refractory Pneumonitis(At days 1, 14, and 28)
- Functional Parameters of Steroid-refractory Pneumonitis by Diffusion Capacity(At days 1, 14, and 28)
- Incidence of Adverse Events(Up to 28 days)
- Functional Parameters of Steroid-refractory Pneumonitis by Spirometry(At days 1, 14, and 28)
- Functional Parameters of Steroid-refractory Pneumonitis by Oxygen Saturation(At days 1, 14, and 28)
- Total Score of Functional Assessment of Cancer Therapy - Lung Version 4(At days 1, 14, and 28)