Official Title
Interventional Study to Evaluate the Efficacy of Therapeutic Plasma Exchange (TPE) Alone or in Combination With Ruxolitinib in COVID-19 Positive Patients With PENN Grade 2, 3, 4 Cytokine Released Syndrome (CRS)
Brief Summary

This protocol will evaluate the efficacy of Therapeutic Plasma Exchange (TPE) alone or in combination with ruxolitinib in COVID positive patients with PENN grade 2, 3, 4 cytokine release syndrome (CRS). It is hypothesized that dual intervention of acute apheretic depletion of cytokines and concomitant suppression of production will produce superior amelioration of the cytokine load and to help to prevent cytokine load rebound. This protocol is envisioned as a pilot study (n=20) for hypothesis generation for future investigation.

Detailed Description

A virally mediated pandemic of 2020 is linked to a novel Beta Coronavirus (COVID-19) sharing
subgenus classification with the severe acute respiratory syndrome (SARS) virus. The
predominant modes of transmission are respiratory aerosolization and contaminated surface
contact. COVID-19 infection is characterized by a wide range of severity and disease
manifestations from asymptomatic to respiratory and multi organ failure. Definitive treatment
is lacking, but there is an increasing awareness of its associated systemic cascade of
inflammatory molecules that offers avenues to explore therapeutically.

Therapeutic plasma exchange (TPE) offers an immediate and scientifically grounded
intervention for the removal of a host of pathogenic antibodies and toxic molecules by
centrifugal separation of plasma or plasma membrane filtration. TPE in conjunction with
Tocilizumab and steroids has been used successfully in the management of severe cytokine
release syndrome (CRS) following chimeric antigen receptor T-cell therapy (CAR-T).

Precedence for consideration of TPE in a variety of inflammatory dominant disease states is
also well known. Interest in adjuvant treatment for management of sepsis and multi organ
dysfunction has been studied. TPE has also been used in three pediatric patients with pH1N1
influenza A acute respiratory failure and hemodynamic shock despite failure of best
supportive care. All three survived with "good functional recovery."

Ruxolitinib is a Janus kinase (JAK) and signal transducer and activator of transcription
(STAT) (JAK/STAT) pathway inhibitor which is FDA approved for polycythemia rubra vera,
myelofibrosis and graft versus host disease. A murine model of CRS following CAR-T cellular
therapy has been developed showing marked elevation of interleukin-6 (IL-6),
interferon-gamma, tumor necrosis factor (TNF) alpha mimicking human CAR-T therapy induced
CRS. Ruxolitinib treated mice demonstrated clinical amelioration and decrement in
inflammatory cytokines. Incyte Corporation has announced plans to launch a Phase III trial of
single agent ruxolitinib for COVID-19 associated cytokine storm.

Cytokine Release Syndrome

Procedure: Therapeutic Plasma Exchange

TPE, five single plasma volume exchanges over 7 days (every day x 2 then every other day x 3) with albumin or FFP replacement if underlying coagulopathy

Drug: Ruxolitinib

TPE, five single plasma volume exchanges over 7 days (every day x 2 then every other day x 3) with albumin or FFP replacement if underlying coagulopathy combined with ruxolitinib 5mg po BID beginning day prior to first TPE and continuing BID for total of 14 days.
Other Name: Therapeutic Plasma Exchange

Eligibility Criteria

Inclusion Criteria:

1. Patients positive for COVID-19 by polymerase chain reaction (PCR) assay or alternative
accepted methodology

2. PENN class 2,3,4 CRS

3. Respiratory insufficiency with supplemental oxygen to maintain O2 sat greater than 89%

4. Clinically positive imaging by chest x-ray (CXR) or CT scan with evidence of bilateral
pulmonary infiltrates, ground glass opacification or other pattern of consolidation
felt likely to be linked to COVID infection or complication thereof

5. Age 12-80 years of age

Exclusion Criteria:

1. Pregnancy

2. Breast feeding

3. Class 3-4 New York Heart Association (NYHA) heart failure

4. Current use of synthetic disease modifying anti-rheumatic drugs (DMARDS) or IL-6
inhibitors or other immunosuppressive therapies outside of number five below

5. Current use of chronic corticosteroids if in excess of prednisone 10mg per day or

6. Suspected or confirmed clinically significant bacterial infection

7. History of tuberculosis (TB)

8. History of HIV

9. History of irritable bowel disease (IBD)

10. JAK inhibitor use within last 30 days

11. Creatinine clearance less than 15 ml / min

12. Absolute neutrophil count < 1000

13. Platelet count < 50,000

14. Clinical assessment that the trial could pose unacceptable risk by study participation

15. Current enrollment on another investigational protocol for COVID-19 induced CRS

16. Stage 4 obstructive lung disease with chronic hypoxic respiratory failure requiring
supplemental O2 at baseline, or interstitial lung disease (ILD) with chronic hypoxic
respiratory failure requiring supplemental O2 at baseline

Eligibility Gender
Eligibility Age
Minimum: 12 Years ~ Maximum: 80 Years
United States

Prisma Health
Greenville, South Carolina, United States

W. Larry Gluck, MD, Principal Investigator
Prisma Health

Prisma Health-Upstate
NCT Number
MeSH Terms
Cytokine Release Syndrome