Purpose

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.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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)

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Supportive Care
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Cohort 1 - Etoposide
Participants that are on ventilation Etoposide 150 mg/m2 daily days 1 and 4 If the treating clinicians feel that the patient initially benefited from etoposide but then has evidence of relapse of cytokine storm, the patient may continue on the standard HLH etoposide schedule of day 8, 11, 18, 25 after discussion with one of the study investigators.
  • Drug: Etoposide
    Etoposide 150 mg/m2 administered intravenously once daily on Days 1 and 4. If the treating clinicians feel that the patient initially benefited from etoposide but then has evidence of relapse of cytokine storm, the patient may continue on the standard HLH etoposide schedule of day 8, 11, 18, 25 after discussion with one of the study investigators.
    Other names:
    • Etopophos
Experimental
Cohort 2 - Etoposide
Participants that are NOT on ventilation Etoposide 150 mg/m2 daily days 1 and 4 Etoposide 150 mg/m2 administered intravenously once daily on Days 1 and 4. If the treating clinicians feel that the patient initially benefited from etoposide but then has evidence of relapse of cytokine storm, the patient may continue on the standard HLH etoposide schedule of day 8, 11, 18, 25 after discussion with one of the study investigators.
  • Drug: Etoposide
    Etoposide 150 mg/m2 administered intravenously once daily on Days 1 and 4. If the treating clinicians feel that the patient initially benefited from etoposide but then has evidence of relapse of cytokine storm, the patient may continue on the standard HLH etoposide schedule of day 8, 11, 18, 25 after discussion with one of the study investigators.
    Other names:
    • Etopophos
No Intervention
Cohort 1 - Control
Standard of care therapy in participants that are on ventilation
No Intervention
Cohort 2 - Control
Standard of care therapy in participants that are NOT on ventilation.

Recruiting Locations

Boston Medical Center
Boston, Massachusetts 02118
Contact:
Annie Jose, BS
617-638-8213
annie.jose@bmc.org

More Details

Status
Recruiting
Sponsor
Boston Medical Center

Study Contact

John Mark Sloan, MD
617-638-7002
mark.sloan@bmc.org

Detailed Description

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.