WithdrawnPhase 3ACTRN12620000844943

C-SMART. COVID-19 Prevention and Treatment in Cancer Arm 4: treatment among cancer patients with severe COVID-19 infection.

COVID-19 Prevention and Treatment in Cancer; a Sequential Multiple Assignment Randomised Trial; C-SMART study Arm 4: Effect of Lenzilumab in cancer patients with severe COVID-19 infection.

Sponsor

Peter MacCallum Cancer Centre

Enrollment

72 participants

Start Date

Sep 1, 2020

Study Type

Interventional

Conditions

Cancer COVID-19

Summary

A multi-centre Australian trial with four arms aims to evaluate several different immune modulating drugs for prevention and treatment of COVID-19 specifically in the cancer population. This study arm (arm 4) is evaluating the effect of Lenzilumab on the treatment of COVID-19 infection in cancer patients with severe COVID-19 infection. Who is it for? You may be eligible to join this study arm if you are aged 18 and above, have any haematological or solid tumour, currently receiving cancer-related treatment, and are hospitalised with a severe COVID-19 infection Study details Participants in this study arm are randomly allocated (by chance) to one of two groups. One group will receive intravenous Lenzilumab over 24 hours while the other group will receive placebo intravenously over 24 hours. Participants will be followed for 60 days to assess effectiveness and safety. This study is one arm of a four arm, sequential multiple assignment randomisation trial where participants may become eligible and transition to different arms and treatments if they become exposed to COVID-19 or are hospitalised with an active moderate/severe COVID-19 infection. It is hoped this research will provide insight into the best practice for prevention and treatment of COVID-19 in cancer patients as emerging standard of care measures are not always suitable to this especially vulnerable population.

Eligibility

Sex: Both males and femalesMin Age: 18 Yearss

Inclusion Criteria10

ARM 4
Age equal to or greater than 18 years of age.
Any haematological or solid tumour
Current or within the last 12 months received cancer related treatment such as chemotherapy, radiotherapy or targeted small molecule, cellular therapy or immune-modulating therapy
Signed written and verbal informed consent by participant or proxy capable of giving consent
Laboratory virological confirmation of SARS-CoV-2 by PCR as per local laboratory assays and COVID-19 diagnosis prior to randomisation
Hospitalised but has not required mechanical ventilation
Pneumonia diagnosed by chest x-ray or computed tomography (CT) revealing infiltrates consistent with pneumonia and SpO2 equal to or less than 94% on room air or requires low-flow oxygen supplementation or requires high-flow oxygen supplementation or non-invasive positive pressure ventilation (NIPPV).
Has not participated in other clinical trials for COVID-19 using an immunomodulating monoclonal antibody or kinase inhibitor. Note that participants on dexamethasone, corticosteroids, remdesivir, convalescent plasma and/or hydroxychloroquine with or without azithromycin are not excluded from the study. Agents that have received emergency use authorization and/or are considered by the study site to be standard treatment at the institution for COVID-19 are permitted provided the agent is not an immunomodulating monoclonal antibody or kinase inhibitor. Participation in clinical trials with remdesivir or convalescent plasma is permitted provided that all other eligibility criteria are met.
Females of childbearing potential must have a negative serum or urine pregnancy test at screening/baseline. Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for 5 months following their last dose of study drug.

Exclusion Criteria10

ARM 4
Invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)
History of pulmonary alveolar proteinosis (PAP).
Women of childbearing potential who are pregnant or breastfeeding.
Known hypersensitivity to lenzilumab or any of its components.
.Use of any FDA-approved anti-IL-6 therapy (eg. tocilizumab, sarilumab, siltukimab), anti-IL-1 therapy (eg. anakinra, canakinumab) or kinase inhibitor (eg.baracitinib, ibrutinib, acalabrutinib) therapy to treat COVID-19 within 8 weeks prior to randomization. Any live vaccine within 8 weeks prior to randomisation. Note that subjects receiving other FDA-approved immunomodulators to treat underlying autoimmune disorders such as rheumatoid arthritis, psoriasis, ankylosing spondylitis, asthma, chronic obstructive pulmonary disease, atopic dermatitis, multiple sclerosis, etc. would not be excluded. Participants on corticosteroids or dexamethasone are not excluded from the study. Note: Participants on convalescent plasma, remdesivir and/or hydroxychloroquine with or without azithromycin are not excluded from the study.
Use of GM-CSF agents (e.g., sargramostim) within 8 weeks prior to randomisation.
Expected survival < 24h in the opinion of the investigator.
Any condition that, in the opinion of the investigator, is likely to interfere with the safety and efficacy of the study treatment or puts the subject at unacceptably high risk from the study.
Participation in another interventional study of COVID-19

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Interventions

ARM 4 - Severe COVID-19 infection Drug: Lenzilumab Dose: 600mg 8 hourly Duration: 24 hours Mode: Intravenous - administered by nurse. adherence: inpatient records Description of study design:

ARM 4 - Severe COVID-19 infection Drug: Lenzilumab Dose: 600mg 8 hourly Duration: 24 hours Mode: Intravenous - administered by nurse. adherence: inpatient records Description of study design: This SMART design specifies that participants entering the trial who have had no known COVID-19 exposure are initially randomised to either low-dose intranasal IFN-a or placebo as pre-exposure prophylaxis against developing COVID-19. Any participants who have a known COVID-19 exposure are randomised to high-dose IFN-a or placebo as a post-exposure prophylaxis against developing COVID-19. If, at any stage after enrolling, a participant develops ‘moderate’ COVID-19, then they are then randomised to either selinexor or placebo, and if at any stage after enrolling the participant develops ‘severe’ COVID-19 they are then randomised to either lenzilumab or placebo. Importantly, participants enrolling into the trial can directly enter any of the four interventions if they meet the appropriate entry criteria.