Hematopoietic and Lymphoid Cell NeoplasmPhase 2NCT04370834
Tocilizumab for Patients With Cancer and COVID-19 Disease
A Phase 2 study testing Tocilizumab in people with Hematopoietic and Lymphoid Cell Neoplasm and Malignant Solid Neoplasm, run by National Cancer Institute (NCI) at 5 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- Hematopoietic and Lymphoid Cell Neoplasm, Malignant Solid Neoplasm, Pneumonia
- What is being tested?
- Tocilizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 5 sitesUnited States
- Study dates
- 28 May 2020to 14 Jan 2021
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
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- 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
- For patients already enrolled on other investigational studies for COVID-19, study investigators should verify that co-enrollment on this study is permissible as per the eligibility of the other study
- Human immunodeficiency virus (HIV)-infected patients are eligible for this trial unless they have opportunistic complications of acquired immunodeficiency syndrome (AIDS) other than the cancer they have
- For patients with evidence of chronic hepatitis B virus (HBV) infection, should be on suppressive therapy, if indicated
- Patients with a history of hepatitis C virus (HCV) infection should be on treatment if indicated
- The effects of tocilizumab on the developing human fetus are unknown
- Pregnancy: Based on animal data, may cause fetal harm. Tocilizumab may be given if in the physician's judgment the patient's life is threatened without potential effective therapy
- Women of childbearing potential must agree to use birth control or remain abstinent for the duration of the study and for at least 28 days following the last dose of tocilizumab. Pregnancy tests should be done based on the discretion of the patient and physician.
- Nursing mothers: Discontinue drug or nursing taking into consideration importance of drug to mother
- Men must agree to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agree to refrain from donating sperm, for the duration of the study and for at least 28 days following the last dose of tocilizumab
- Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity (IDMC) who have a legally-authorized representative (LAR) and/or family member available will also be eligible
Who cannot join
- 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
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- 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
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
University Medical Center of Southern Nevada
Las Vegas, Nevada, 89102
Summerlin Hospital Medical Center
Las Vegas, Nevada, 89144
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Valley Medical Center
Renton, Washington, 98055
National Cancer Institute
Rockville, Maryland, 20850
About this study
Official title: Tocilizumab in Hospitalized Cancer Patients With Coronavirus 2019 (SARS-CoV-2) and Severe Complications of Coronavirus Disease 19 (COVID-19)
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.
Read the detailed description
PRIMARY OBJECTIVES:
- To enhance access to tocilizumab for patients who cannot participate in the randomized COVACTA trial with specific emphasis on patients with cancer, especially those who belong to high-risk and minority populations and children.
II. To provide observations on clinical outcomes associated with tocilizumab administration in cancer patients with severe acute respiratory syndrome (SARS) coronavirus 2 (COVID-19) disease.
SECONDARY OBJECTIVE:
- To estimate the proportion of patients whose level of institutional care does not further escalate following administration of tocilizumab.
EXPLORATORY OBJECTIVES:
- To estimate the number of days intensive care unit (ICU) patients spent in the ICU.
II. To evaluate the mortality rate of patients:
IIa. 30-day and 60-day mortality in patients in the ICU.
IIb. Evaluate the 14-, 30- and 60-day mortality rate following infusion of tocilizumab.
III. To evaluate overall survival.
IV. To describe the proportion of patients progressing to ventilator support after tocilizumab therapy.
- Evaluate the clinical course following administration of tocilizumab.
Va. To evaluate the development of additional infections.
Vb. To evaluate the side effects following tocilizumab.
Vc. To evaluate impact on inflammatory markers.
VI. Evaluate the duration of time:
VIa. To removal from mechanical ventilator support.
VIb. To step-down of institutional care requirements.
VIc. To discharge from the ICU to lower level.
VId. To hospital discharge.
VIe. To resolution of clinical symptoms.
VIf. To time of defervescence.
VIg. To normalization of disease-related laboratory abnormalities.
VII. Exploratory biologic correlates.
VIIa. To evaluate cytokine levels pre and post-tocilizumab, specifically evaluating IL-6.
VIIb. To evaluate SARS-coronavirus (CoV)-2 viral loads pre and post-tocilizumab.
VIIc. To determine the pharmacokinetics of tocilizumab in order to facilitate exposure-response analysis.
VIId. To correlate clinical outcomes with changes in cytokine levels and SARS-CoV-2 viral loads.
OUTLINE:
Patients receive tocilizumab intravenously (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.
After completion of study treatment, patients are followed up for at least 60 days, and, when possible, up to 1 year.
- Conditions
- Hematopoietic and Lymphoid Cell Neoplasm, Malignant Solid Neoplasm, Pneumonia, Pneumonitis, Severe Acute Respiratory Distress Syndrome, Symptomatic COVID-19 Infection Laboratory-Confirmed
- Being tested
- Tocilizumab
- Medical subject headings
- Hematologic Neoplasms, Pneumonia, Respiratory Distress Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TocilizumabBiological
Also called 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
Given IV
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: Tocilizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With at Least 1 Point Reduction in Score on 7-category Clinical Status Ordinal Scale
7-category Clinical Status Ordinal Scale:
- Discharge
- Non-ICU, hospital ward, No O2
- Non-ICU, hospital ward, on O2
- ICU or non-ICU, requires non-invasive ventilatory support or high flow O2
- ICU requires mechanical or imminent ventilation/intubation
- ICU requires ECMO and additional O2 support and organ support, e.g. vasopressors, renal replacement therapy
- Death
Measured: Day 14 after tocilizumab administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2020
- Study start28 May 2020
- Primary completion14 Jan 2021
- Study completion14 Jan 2021
Why it stopped: Other - Randomized data no longer support continuation
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hematopoietic and Lymphoid Cell NeoplasmStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Richard F Little, Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04370834
- Sponsor's protocol ID
- NCI-2020-02987
- Other IDs
- NCI-2020-02987, TRC-10446, TRC-10446
- Status last verified
- Jan 2025
- First submitted
- 30 Apr 2020
- Last updated
- 4 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.