Tocilizumab for Patients With Cancer and COVID-19 Disease

NCT04370834 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: NCI-2020-02987TRC-10446
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

Hematopoietic and Lymphoid Cell Neoplasm; Malignant Solid Neoplasm; Pneumonia; Pneumonitis; Severe Acute Respiratory Distress Syndrome; Symptomatic COVID-19 Infection Laboratory-Confirmed

Outcome Measures

Primary Outcomes (1)

• Number of Participants With at Least 1 Point Reduction in Score on 7-category Clinical Status Ordinal Scale

  7-category Clinical Status Ordinal Scale: 1. Discharge 2. Non-ICU, hospital ward, No O2 3. Non-ICU, hospital ward, on O2 4. ICU or non-ICU, requires non-invasive ventilatory support or high flow O2 5. ICU requires mechanical or imminent ventilation/intubation 6. ICU requires ECMO and additional O2 support and organ support, e.g. vasopressors, renal replacement therapy 7. Death

  Day 14 after tocilizumab administration

Study Arms (1)

Other (tocilizumab)

EXPERIMENTAL

Patients receive tocilizumab IV over 60 minutes. A second dose may be given if there is sustained or recurrent fever, no decrease or not more than a 1-category improvement on the 7-category ordinal scale (only stabilization or partial improvement following first dose), or a \>= 1-category worsening on the 7-category ordinal scale from nadir.

Biological: Tocilizumab

Interventions

Tocilizumab BIOLOGICAL

Given IV

Also known as: Actemra, Immunoglobulin G1, Anti-(Human Interleukin 6 Receptor) (Human-Mouse Monoclonal MRA Heavy Chain), Disulfide with Human-Mouse Monoclonal MRA Kappa-Chain, Dimer, MRA, R-1569, RoActemra

Other (tocilizumab)

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (5)

National Cancer Institute

Rockville, Maryland, 20850, United States

Location

University Medical Center of Southern Nevada

Las Vegas, Nevada, 89102, United States

Location

Summerlin Hospital Medical Center

Las Vegas, Nevada, 89144, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Valley Medical Center

Renton, Washington, 98055, United States

Location

MeSH Terms

Conditions

Hematologic Neoplasms; Pneumonia; Respiratory Distress Syndrome

Interventions

tocilizumab; Immunoglobulin G; Disulfides

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Intervention Hierarchy (Ancestors)

Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals

Limitations and Caveats

Early termination as randomized data did not support continuation.

Results Point of Contact

• Title: Dr. Richard Little, Principal Investigator
• Organization: National Cancer Institute

littler@mail.nih.gov

240-276-6093

Study Officials

• Richard F Little

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2020
• First Posted: May 1, 2020
• Study Start: May 28, 2020
• Primary Completion: January 14, 2021
• Study Completion: January 14, 2021
• Last Updated: February 4, 2025
• Results First Posted: June 4, 2021

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share

Locations

US (5)