Tocilizumab for Patients With Cancer and COVID-19 Disease
Condition: Hematopoietic and Lymphoid Cell Neoplasm; Malignant Solid Neoplasm; Pneumonia; Pneumonitis; Severe Acute Respiratory Distress Syndrome; Symptomatic COVID-19 Infection Laboratory-Confirmed
MeSH terms: COVID-19; Pneumonia; Laboratory Infection; Neoplasms; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
Intervention: Tocilizumab
Intervention description: Given IV
Intervention MeSH terms: Immunoglobulins; Immunoglobulin G
Phase: Phase 2
Study type: Interventional
Primary purpose: Other
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 2 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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

        Exclusion Criteria:

          -  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