Etoposide in Patients With COVID-19 Infection
Etoposide in Patients With COVID-19 Infection
This is a randomized, open-label phase II study designed to evaluate the safety and efficacy
 of etoposide in patients with the 2019 novel coronavirus (COVID-19) infection. Randomization
 will be performed with a 3:1 allocation ratio. Treatment will be comprised of etoposide
 administered intravenously at a dose of 150 mg/m2 on Days 1 and 4 in patients with COVID-19
 infection meeting eligibility criteria. Subsequent doses of etoposide will be allowed if the
 investigator and treating physician believe the patient had clinical benefit from etoposide
 therapy but subsequently has evidence of recurrent clinical deterioration. Subjects
 randomized to control will receive standard of care treatment. No placebo will be used.
This is a randomized, open-label phase II study designed to evaluate the safety and efficacy
 of etoposide in patients with the 2019 novel coronavirus (COVID-19) infection. Randomization
 will be performed with a 3:1 allocation ratio. Treatment will be comprised of etoposide
 administered intravenously at a dose of 150 mg/m2 on Days 1 and 4 in patients with COVID-19
 infection meeting eligibility criteria. Subsequent doses of etoposide will be allowed if the
 investigator and treating physician believe the patient had clinical benefit from etoposide
 therapy but subsequently has evidence of recurrent clinical deterioration. Subjects
 randomized to control will receive standard of care treatment. No placebo will be used.

 The rationale for the use of etoposide to treat the cytokine storm in COVID-19 is the high
 mortality associated with the hyperinflammatory response to the virus, which is similar to
 that seen in other secondary types of Hemophagocytic lymphohistiocytosis. Autopsy studies of
 Acute respiratory distress syndrome (ARDS) in COVID patients show a high number of cytolytic
 T cells in the lungs of such patients. Early autopsy results of COVID patients at Boston
 Medical Center demonstrate significant hemophagocytosis in lymph nodes and spleen. Comparable
 studies in the related coronavirus infection severe acute respiratory syndrome (SARS) have
 demonstrated hemophagocytosis, a hallmark of HLH.15 By targeting the T cells and monocytes
 driving the cytokine storm in patients with the more severe forms of COVID infection, we hope
 to alleviate the progression of lung and multi-organ dysfunction characteristic of patients
 who die from this illness.
Inclusion Criteria:

 -  Confirmed COVID-19 infection

 -  Evidence of cytokine storm defined as:

 -  Peak ferritin > 10,000 ng/mL OR

 -  Peak ferritin > 500 ng/mL and one or more of the following at any time during
 hospital admission: Lactate dehydrogenase > 500 U/L, d-dimer >1000 ng/mL,
 C-reactive protein > 100 mg/L, or white blood count> 15 k/microlitre

 Cohort 1: Intubated status as a result of COVID infection-associated respiratory illness.

 Cohort 2 (if activated): Evidence of progressive respiratory failure (requiring >4 L/min of
 supplemental oxygen to maintain oxygen saturation greater than 92%) without intubation;

 Exclusion Criteria:

 -  Pregnancy or breastfeeding

 -  History of severe hypersensitivity to etoposide products

 -  Absolute neutrophil count (ANC) < 1000 cells/mm3

 -  Platelet count <50,000/mm3

 -  Bilirubin > 3.0 mg/dL

 -  Aspartate OR alanine aminotransferase > 5.0 x upper limit of normal

 -  Creatinine Clearance < 15 mL/min (calculated by Cockcroft Fault formula)

 -  Requiring continuous renal replacement therapy

 -  Requiring vasopressors

 -  Requiring extracorporeal membrane oxygenation (ECMO)

 -  Other active, life-threatening infections

 -  Anti-cytokine treatment (including anakinra or Interleukin 6 antibodies eg
 tocilizumab, sarilumab) administration within three half-lives of the medication used

 -  Hydroxychloroquine, colchicine, azithromycin, doxycycline-if administered for COVID
 infection-must be discontinued for at least 24 hours prior to randomization.

 -  Has a history or current evidence of any condition, therapy or laboratory abnormality
 that might confound the results of the study, interfere with subject participation, or
 is not in the best interest of the patient to participate, in the opinion of the
 investigator.

 -  Inability to consent and no legally authorized representative

 -  Poorly controlled HIV infection (CD4 count <100 cells/mm3)