Tocilizumab in Hospitalized Cancer Patients With Coronavirus 2019 (SARS-CoV-2) and Severe Complications of Coronavirus Disease 19 (COVID-19)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 5
- 主要终点
- Number of Participants With at Least 1 Point Reduction in Score on 7-category Clinical Status Ordinal Scale
研究概览
简要总结
This phase II expanded access trial will study how well tocilizumab works in reducing the serious symptoms including pneumonitis (severe acute respiratory distress) in patients with cancer and COVID-19. COVID-19 is caused by the SARS-CoV-2 virus. COVID-19 can be associated with an inflammatory response by the immune system which may also cause symptoms of COVID-19 to worsen. This inflammation may be called "cytokine storm," which can cause widespread problems in the body. Tocilizumab is a medicine designed to block the action of a protein called interleukin-6 (IL-6) that is involved with the immune system and is known to be a key factor for problems with excessive inflammation. Tocilizumab is effective in treating "cytokine storm" from a type of cancer immunotherapy and may be effective in reducing the inflammatory response and "cytokine storm" seen in severe COVID-19 disease. Treating the inflammation may help to reduce symptoms, improve the ability to breathe without a breathing machine (ventilator), and prevent patients from having more complications.
详细描述
PRIMARY OBJECTIVES:
I. To enhance access to tocilizumab for patients who cannot participate in the randomized COVACTA trial with specific emphasis on patients with cancer, especially those who belong to high-risk and minority populations and children.
II. To provide observations on clinical outcomes associated with tocilizumab administration in cancer patients with severe acute respiratory syndrome (SARS) coronavirus 2 (COVID-19) disease.
SECONDARY OBJECTIVE:
I. To estimate the proportion of patients whose level of institutional care does not further escalate following administration of tocilizumab.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must have an active cancer diagnosis or have completed therapy within 12 months of initiation of protocol specified therapy. This includes:
- •Subjects with a new cancer diagnosis who have not yet initiated cancer therapy
- •Subjects on active or have recently completed cancer-directed therapy including chemotherapy, radiation therapy, immunotherapy or hormonal therapy amongst others
- •Myelosuppressive chemotherapy for patients in remission (e.g., adjuvant chemotherapy for breast cancer, acute myeloid leukemia [AML] consolidation) is prohibited until clinical recovery (1 or 2 on the 7-category ordinal scale)
- •Subjects on any investigational therapy for their underlying cancer, investigational COVID-19 anti-viral agents, or convalescent serum aimed at treating COVID-19 disease are eligible. Investigators are reminded to check whether the other investigational study(s) the patient is participating on specifically exclude tocilizumab and to adjudicate best clinical management decision for the specific patient
- •Subjects who have undergone hematopoietic stem cell transplant within the past 12 months, or are continued on graft versus host disease (GVHD) therapy, are also eligible
- •COVID-19 Diagnosis: Patients hospitalized with COVID-19 pneumonia confirmed by:
- •Radiographic findings concerning for COVID-19 pneumonia AND
- •Confirmatory SARS-CoV-2 positive result using any testing assay, or (with or without a confirmatory test) with suspicion of COVID-19 disease owing to belonging to a high-risk demographic group or living and/or working in high-risk settings or with known exposure AND
- •Oxygen saturation (SpO2) on room air =< 93% or PaO2/FiO2 < 300 mmHg
- •Age >= 2 years
- •Patients must have adequate organ function as assessed by the treating investigator to administer tocilizumab
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 10 x institutional upper limit of normal
- •Patients with low blood counts attributable to cancer therapy or underlying malignancy are eligible
- •Patients may be on other therapies for COVID-19 including investigational and not limited to corticosteroids, azithromycin, chloroquine, hydroxychloroquine
- •For patients already enrolled on other investigational studies for COVID-19, study investigators should verify that co-enrollment on this study is permissible as per the eligibility of the other study
- •Human immunodeficiency virus (HIV)-infected patients are eligible for this trial unless they have opportunistic complications of acquired immunodeficiency syndrome (AIDS) other than the cancer they have
- •For patients with evidence of chronic hepatitis B virus (HBV) infection, should be on suppressive therapy, if indicated
- •Patients with a history of hepatitis C virus (HCV) infection should be on treatment if indicated
- •The effects of tocilizumab on the developing human fetus are unknown
- •Pregnancy: Based on animal data, may cause fetal harm. Tocilizumab may be given if in the physician's judgment the patient's life is threatened without potential effective therapy
- •Women of childbearing potential must agree to use birth control or remain abstinent for the duration of the study and for at least 28 days following the last dose of tocilizumab. Pregnancy tests should be done based on the discretion of the patient and physician.
- •Nursing mothers: Discontinue drug or nursing taking into consideration importance of drug to mother
- •Men must agree to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agree to refrain from donating sperm, for the duration of the study and for at least 28 days following the last dose of tocilizumab
- •Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity (IDMC) who have a legally-authorized representative (LAR) and/or family member available will also be eligible
排除标准
- •Prior or concurrent utilization of IL-6 specific targeting strategies for treatment of COVID-19 that showed no benefit after maximum dosing; (patients who have only received 1 prior dose and there was evidence of potential benefit may be eligible)
- •This includes siltuximab, tocilizumab, and sarilumab
- •Known hypersensitivity or history of severe allergic reaction to tocilizumab or other monoclonal antibodies
- •Any serious medical condition or active uncontrolled infections (besides COVID-19) that, in the investigator's judgement, preclude the subject's safe participation in the study
- •Examples: Active tuberculosis (TB) infection
- •Active diverticulitis because of severe flairs in disease leading risk of bowel perforation
- •Patients in whom, in the opinion of the treating physician, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments, will be excluded from the study
- •Patients receiving or planning to receive any investigational agents other than tocilizumab are ineligible for this study, with the following exceptions:
- •Investigational agents directed at a patient's underlying cancer are allowed.
- •Investigational SARS-CoV-2 anti-viral agents
- •Convalescent serum directed at COVID-19 disease
研究组 & 干预措施
Other (tocilizumab)
Patients receive tocilizumab IV over 60 minutes. A second dose may be given if there is sustained or recurrent fever, no decrease or not more than a 1-category improvement on the 7-category ordinal scale (only stabilization or partial improvement following first dose), or a >= 1-category worsening on the 7-category ordinal scale from nadir.
干预措施: Tocilizumab (Biological)
结局指标
主要结局
Number of Participants With at Least 1 Point Reduction in Score on 7-category Clinical Status Ordinal Scale
时间窗: Day 14 after tocilizumab administration
7-category Clinical Status Ordinal Scale: 1. Discharge 2. Non-ICU, hospital ward, No O2 3. Non-ICU, hospital ward, on O2 4. ICU or non-ICU, requires non-invasive ventilatory support or high flow O2 5. ICU requires mechanical or imminent ventilation/intubation 6. ICU requires ECMO and additional O2 support and organ support, e.g. vasopressors, renal replacement therapy 7. Death
次要结局
未报告次要终点