COVID-19 Prevention and Treatment in Cancer; a Sequential Multiple Assignment Randomised Trial;

Inclusion Criteria:

• ARM 1:

1. Age equal to or greater than 18 years old
2. Any haematological or solid tumour
3. Signed written and verbal informed consent
4. Willingness to inform the study nurse/co-ordinator of COVID-19 testing
5. Willingness to perform a self-collect nose/throat swab ARM 2
6. Age equal to or greater than 18 years old.
7. Any haematological or solid tumour
8. Signed written and verbal informed consent
9. Have been exposed to a known COVID-19 case within the last 72 hours, defined by thecurrent Department of Health and Human services such as household contact, 15 minutesof face to face exposure, 2 hours in close space.
10. Willingness to inform the study nurse/co-ordinator of COVID-19 testing
11. Willingness to perform a self-collect nose/throat swab ARM 3 1. Age equal to or greater than 18 years of age. 2. Any haematological or solidtumour 3. Current or within the last 12 months received cancer related treatment such aschemotherapy, radiotherapy or targeted small molecule, cellular therapy orimmune-modulating therapy 4. Signed written and verbal informed consent 5. Laboratoryconfirmation of SARS-CoV-2 by PCR as per local laboratory assays 6. Hospitalised 7.Symptoms of COVID-19 such as:
12. Fever equal to or greater than 38 degrees Celsius OR
13. Tachypnoea respiratory rate equal to or greater than 20 breaths/min OR
14. Pulse Oxygen saturation (SpO2) equal to or less than 94% 8. Concurrent standard ofcare antimicrobials, antivirals are allowed. 9. Female and male patients of childbearing potential will use highly effective contraception. In female child bearingpotential participants a negative urine pregnancy test will be required. ARM 4
15. Age equal to or greater than 18 years of age.
16. Any haematological or solid tumour
17. Current or within the last 12 months received cancer related treatment such aschemotherapy, radiotherapy or targeted small molecule, cellular therapy orimmune-modulating therapy
18. Signed written and verbal informed consent by participant or proxy capable ofgiving consent
19. Laboratory virological confirmation of SARS-CoV-2 by PCR as per local laboratoryassays and COVID-19 diagnosis prior to randomisation
20. Hospitalised but has not required mechanical ventilation
21. Pneumonia diagnosed by chest x-ray or computed tomography (CT) revealinginfiltrates consistent with pneumonia and SpO2 equal to or less than 94% on roomair or requires low-flow oxygen supplementation or requires high-flow oxygensupplementation or non-invasive positive pressure ventilation (NIPPV).
22. Has not participated in other clinical trials for COVID-19 using animmunomodulating monoclonal antibody or kinase inhibitor. Note that participantson dexamethasone, corticosteroids, remdesivir, convalescent plasma and/orhydroxychloroquine with or without azithromycin are not excluded from the study.Agents that have received emergency use authorization and/or are considered bythe study site to be standard treatment at the institution for COVID-19 arepermitted provided the agent is not an immunomodulating monoclonal antibody orkinase inhibitor. Participation in clinical trials with remdesivir orconvalescent plasma is permitted provided that all other eligibility criteria aremet.
23. Females of childbearing potential must have a negative serum or urine pregnancytest at screening/baseline. Women of childbearing potential must agree to useadequate 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 Criteria:

• ARM 1

1. Previous diagnosis of COVID-19 (microbiologically proven, either symptomaticor asymptomatic)
2. Have been exposed to a known COVID-19 case within the last 72 hours, definedby the current Department of Health and Human services such as householdcontact, 15 minutes of face to face exposure, 2 hours in close space.
3. Any contra-indication to intra-nasal IFN-a such as severe nasal bleedingrequiring intervention, nasal malignancy, nasal deformity, radiotherapy tothe nasopharynx and/or oropharynx
4. Pregnant or breast-feeding women, or women who wish to become pregnantduring the course of the study
5. Participant unable to return for regular follow-up
6. Life expectancy of less than 4 months
7. Participant already included in another intervention study on the preventionof COVID-19
8. Currently unwell with influenza-like symptoms - if participant is found tobe COVID-19 negative and becomes asymptomatic, they can be reconsidered forparticipation ARM 2
9. Previous diagnosis of COVID-19 (microbiologically proven, either symptomatic orasymptomatic)
10. Any contra-indication to intra-nasal IFN-a such as severe nasal bleedingrequiring intervention, nasal malignancy, nasal deformity, radiotherapy to thenasopharynx and/or oropharynx
11. Pregnant or breast-feeding women, or women who wish to become pregnant during thecourse of the study
12. Patient unable to return for follow-up
13. Life expectancy of less than 1 month
14. Patient already included in another intervention study on the prevention ofCOVID-19
15. Currently unwell with influenza-like symptoms ARM 3
16. Unable to take oral medication
17. Any known allergic reactions to selinexor or concomitant medication-relatedcontra-indications to selinexor.
18. Severe critical COVID-19 infection defined as:
19. Requiring invasive or non-invasive mechanical ventilation, ECMO
20. Anticipated unlikely to survive within 48 hours
21. In the opinion of the investigator and primary oncologist, participation in thestudy would not be in the best interests of the participant
22. Severe renal impairment defined as creatinine clearance (CrCL) < 20ml/min ascalculated using the Cockcroft Gault formula
23. Severe hepatic impairment defined as aspartate transaminase (AST) or alaninetransaminase (ALT) > 5 x upper limit of normal (ULN) ARM 4
24. Invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) 2.History of pulmonary alveolar proteinosis (PAP). 3. Women of childbearing potentialwho are pregnant or breastfeeding. 4. Known hypersensitivity to lenzilumab or any ofits components. 5 .Use of any FDA-approved anti-IL-6 therapy (eg. tocilizumab,sarilumab, siltukimab), anti-IL-1 therapy (eg. anakinra, canakinumab) or kinaseinhibitor (eg.baracitinib, ibrutinib, acalabrutinib) therapy to treat COVID-19 within 8 weeks prior to randomization. Any live vaccine within 8 weeks prior torandomisation. Note that subjects receiving other FDA-approved immunomodulators totreat underlying autoimmune disorders such as rheumatoid arthritis, psoriasis,ankylosing spondylitis, asthma, chronic obstructive pulmonary disease, atopicdermatitis, multiple sclerosis, etc. would not be excluded. Participants oncorticosteroids or dexamethasone are not excluded from the study. Note: Participantson convalescent plasma, remdesivir and/or hydroxychloroquine with or withoutazithromycin are not excluded from the study.
25. Use of GM-CSF agents (e.g., sargramostim) within 8 weeks prior to randomisation.
26. Expected survival < 24h in the opinion of the investigator. 8. Any condition that,in the opinion of the investigator, is likely to interfere with the safety andefficacy of the study treatment or puts the subject at unacceptably high risk from thestudy.
27. Participation in another interventional study of COVID-19