Therapeutic Plasma Exchange Alone or in Combination With Ruxolitinib in COVID-19 Associated CRS

NCT04374149 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: PHU COVID-19-001
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Cytokine Release Syndrome; COVID19

Outcome Measures

Primary Outcomes (2)

• C-reactive Protein (CRP) Levels at Baseline and Day 14

  Defined as decreasing the CRP level from baseline to study day 14

  Baseline and at Day 14

• Cytokine Levels at Baseline and Day 14

  Defined as decreasing the interleukin (IL) IL-6 and IL-10 load and the tumor necrosis factor (TNF) load from baseline to study day 14

  Baseline and at Day 14

Study Arms (2)

1 - TPE Alone

EXPERIMENTAL

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

Procedure: Therapeutic Plasma Exchange

2 - TPE Plus Ruxolitinib

EXPERIMENTAL

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

Procedure: Therapeutic Plasma Exchange; Drug: Ruxolitinib

Interventions

Therapeutic Plasma Exchange PROCEDURE

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

1 - TPE Alone; 2 - TPE Plus Ruxolitinib

Ruxolitinib DRUG

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.

Also known as: Therapeutic Plasma Exchange

2 - TPE Plus Ruxolitinib

Eligibility Criteria

• Age: 12 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients positive for COVID-19 by polymerase chain reaction (PCR) assay or alternative accepted methodology
• PENN class 2,3,4 CRS
• Respiratory insufficiency with supplemental oxygen to maintain O2 sat greater than 89%
• 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
• Age 12-80 years of age

You may not qualify if:

• Pregnancy
• Breast feeding
• Class 3-4 New York Heart Association (NYHA) heart failure
• Current use of synthetic disease modifying anti-rheumatic drugs (DMARDS) or IL-6 inhibitors or other immunosuppressive therapies outside of number five below
• Current use of chronic corticosteroids if in excess of prednisone 10mg per day or equivalent
• Suspected or confirmed clinically significant bacterial infection
• History of tuberculosis (TB)
• History of HIV
• History of irritable bowel disease (IBD)
• JAK inhibitor use within last 30 days
• Creatinine clearance less than 15 ml / min
• Absolute neutrophil count \< 1000
• Platelet count \< 50,000
• Clinical assessment that the trial could pose unacceptable risk by study participation
• Current enrollment on another investigational protocol for COVID-19 induced CRS

Sponsors & Collaborators

• Prisma Health-Upstate: lead

Study Sites (1)

Prisma Health

Greenville, South Carolina, 29605, United States

Location

Related Publications (10)

• Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huang CL, Chen HD, Chen J, Luo Y, Guo H, Jiang RD, Liu MQ, Chen Y, Shen XR, Wang X, Zheng XS, Zhao K, Chen QJ, Deng F, Liu LL, Yan B, Zhan FX, Wang YY, Xiao GF, Shi ZL. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020 Mar;579(7798):270-273. doi: 10.1038/s41586-020-2012-7. Epub 2020 Feb 3.

  PMID: 32015507 BACKGROUND

• Jernigan DB; CDC COVID-19 Response Team. Update: Public Health Response to the Coronavirus Disease 2019 Outbreak - United States, February 24, 2020. MMWR Morb Mortal Wkly Rep. 2020 Feb 28;69(8):216-219. doi: 10.15585/mmwr.mm6908e1.

  PMID: 32106216 BACKGROUND

• Conti P, Ronconi G, Caraffa A, Gallenga CE, Ross R, Frydas I, Kritas SK. Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVI-19 or SARS-CoV-2): anti-inflammatory strategies. J Biol Regul Homeost Agents. 2020 March-April,;34(2):327-331. doi: 10.23812/CONTI-E.

  PMID: 32171193 BACKGROUND

• Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ; HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020 Mar 28;395(10229):1033-1034. doi: 10.1016/S0140-6736(20)30628-0. Epub 2020 Mar 16. No abstract available.

  PMID: 32192578 BACKGROUND

• Xiao X, He X, Li Q, Zhang H, Meng J, Jiang Y, Deng Q, Zhao M. Plasma Exchange Can Be an Alternative Therapeutic Modality for Severe Cytokine Release Syndrome after Chimeric Antigen Receptor-T Cell Infusion: A Case Report. Clin Cancer Res. 2019 Jan 1;25(1):29-34. doi: 10.1158/1078-0432.CCR-18-1379. Epub 2018 Oct 15.

  PMID: 30322878 BACKGROUND

• Busund R, Koukline V, Utrobin U, Nedashkovsky E. Plasmapheresis in severe sepsis and septic shock: a prospective, randomised, controlled trial. Intensive Care Med. 2002 Oct;28(10):1434-9. doi: 10.1007/s00134-002-1410-7. Epub 2002 Jul 23.

  PMID: 12373468 BACKGROUND

• Rimmer E, Houston BL, Kumar A, Abou-Setta AM, Friesen C, Marshall JC, Rock G, Turgeon AF, Cook DJ, Houston DS, Zarychanski R. The efficacy and safety of plasma exchange in patients with sepsis and septic shock: a systematic review and meta-analysis. Crit Care. 2014 Dec 20;18(6):699. doi: 10.1186/s13054-014-0699-2.

  PMID: 25527094 BACKGROUND

• Patel P, Nandwani V, Vanchiere J, Conrad SA, Scott LK. Use of therapeutic plasma exchange as a rescue therapy in 2009 pH1N1 influenza A--an associated respiratory failure and hemodynamic shock. Pediatr Crit Care Med. 2011 Mar;12(2):e87-9. doi: 10.1097/PCC.0b013e3181e2a569.

  PMID: 20453703 BACKGROUND

• Porter D, Frey N, Wood PA, Weng Y, Grupp SA. Grading of cytokine release syndrome associated with the CAR T cell therapy tisagenlecleucel. J Hematol Oncol. 2018 Mar 2;11(1):35. doi: 10.1186/s13045-018-0571-y.

  PMID: 29499750 BACKGROUND

• Gluck WL, Callahan SP, Brevetta RA, Stenbit AE, Smith WM, Martin JC, Blenda AV, Arce S, Edenfield WJ. Efficacy of therapeutic plasma exchange in the treatment of penn class 3 and 4 cytokine release syndrome complicating COVID-19. Respir Med. 2020 Dec;175:106188. doi: 10.1016/j.rmed.2020.106188. Epub 2020 Nov 7.

  PMID: 33190086 DERIVED

MeSH Terms

Conditions

Cytokine Release Syndrome; COVID-19

Interventions

Plasma Exchange; ruxolitinib

Condition Hierarchy (Ancestors)

Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Blood Transfusion; Biological Therapy; Therapeutics; Plasmapheresis; Blood Component Removal; Sorption Detoxification; Extracorporeal Circulation; Surgical Procedures, Operative

Limitations and Caveats

Pilot study with small sample size. The imbalance between cohorts with respect to previous or concomitant therapy reflects the greater adoption of convalescent plasma and antiviral medication over the time span of the study.

Results Point of Contact

• Title: Dr. Julie Martin, Director of Cancer Research
• Organization: Prisma Health

julie.martin@prismahealth.org

(864) 455-3667

Study Officials

• W. Larry Gluck, MD

  Prisma Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2020
• First Posted: May 5, 2020
• Study Start: April 30, 2020
• Primary Completion: September 30, 2020
• Study Completion: December 1, 2020
• Last Updated: December 2, 2021
• Results First Posted: December 2, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Available April 2021 through December 2021
• Access Criteria: Data can be requested from the Principal Investigator via email and should include a description of the request and the associated project or use of the data.

Locations

US (1)