C-SMART.

INTERVENTION: 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. CONDITION: Cancer ‐ Any cancer COVID‐19;Cancer; ; COVID‐19 ; Cancer Infection ‐ Other infectious diseases Respiratory ‐ Other respiratory disorders / diseases PRIMARY OUTCOME: ARM 4:; time to clinical improvement (defined as a two point reduction in clinical progress ordinal scale) or discharge from hospital, whichever occurs first.; assessed using medical records[28 days from baseline] SECONDARY OUTCOME: ARM 4: secondary outcome 1 ; Incidence of all cause death by day 28 and 60[day 28 from baseline and day 60 from baseline] ARM 4: secondary outcome 10 ; composite outcome: Organ failure free days and proportion who did not develop organ failure. assessed using medical records.[any time up to 60 days from baseline] ARM 4: secondary outcome 11 ; composite outcome: Incidence and duration of ICU admission. assessed using medical records[at discharge or by day 60 from baseline. ] ARM 4: secondary outcome 12 ; composite outcome: incidence and duration of supplemental oxygen use. assessed using medical records[any time up to 60 days from baseline] ARM 4: secondary outcome 13 ; Time to clinical improvement defined as National Early Warning Score 2 (NEWS2) of <2 maintained for 24 hours. ; assessed using medical records.[any time up to 60 days from baseline] ARM 4: secondary outcome 14 ; incidence of non‐invasive ventilation. assessed using medical records[any time up to 60 days from baseline] ARM 4: secondary outcome 15 ; composite outcome: number of participants alive and off oxygen at day 60. assessed using medical records.[any time up to 60 days from baseline] ARM 4: secondary outcome 16 ; proportion of participants who had improved oxygenation for >48 hours. assessed using medical records[any time up to 28 days from baseline] ARM 4: secondary outcome 17 ; Incidence of adverse events based on the national cancer institute CTCAE v5 ; examples of possible/probable adverse events may include (but are not limited to): ; • Infection of urinary tract ; • Pain in limbs ; • Headache ; • Painful menstruation, typically involving abdominal cramps ; • Throat pain ; • Hot flush ; Assessed using medical records and patient symptom diary.[any time up to day 28 from baseline.] ARM 4: secondary outcome 18 ; incidence of SAEs based on NCI CTCAE v5. ; examples of possible/probable adverse events listed in known possible serious adverse events could include (but are not limited to): ; • Heart attack ; • Inflammation of the appendix (i.e. a pouch at the start of the large intestine) ; • Infection of lungs ; • Suicidal attempt ; • Hypoxia ‐ lack of sufficient oxygen in the tissues ; ; This will be assessed using medical records[any time up to 28 days from baseline.] ARM 4: secondary outcome 19 ; change in nasopharngeal SARS‐CoV‐2 viral load shedding. assessed using qPCR.[any time up to day 60 from baseline] ARM 4: secondary outcome 2 ; Time to all‐cause mortality[any time up to 60 days from baseline] ARM 4: secondary outcome 3 ‐ Composite outcome. ; Illness severity of COVID‐19, defined as the maximal score on the World Health Organization (WHO)’s clinical progression ordinal scale ranging from 0 (uninfected) to 10 (death) ; a) Proportion who have recovered (defined as 0‐4) ; b) Proportion who had 1 point improvement ; c) Proportion who had 2 point improvement[any time up to 60 days from baseline ; ] ARM 4: secondary outcome 4 ; Incidence of ARDS. ; assessed using medical records[any time up to 60 days from baseline] ARM 4: secondary outcome 5 ; incidence of HLH. assessed using medical records[any time up to 60 days from baseline] ARM 4: secondary outcome 6 ; Duration of hospitalisation. assessed using hospital medical records. ; [at discharge] ARM 4: secondary outcome 7 ; Proportion discharged from hospital. assessed using medical records ; [at discharge] ARM 4: secondary outcome 8 ; Incidence of mechanical ventilation up to day 28. ; assessed using medical records[any time up day 28 from baseline] ARM 4: secondary outcome 9 ; composite outcome: Ventilator‐free days and proportion who did not receive invasive mechanical ventilation. assessed using medical records[any time up to 60 days from baseline] INCLUSION CRITERIA: ARM 4 1. Age equal to or greater than 18 years of age. 2. Any haematological or solid tumour 3. 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 4. Signed written and verbal informed consent by participant or proxy capable of giving consent 5. Laboratory virological confirmation of SARS‐CoV‐2 by PCR as per local laboratory assays and COVID‐19 diagnosis prior to randomisation 6. Hospitalised but has not required mechanical ventilation 7. 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). 8. Has not participated in other clinical trials for COVID‐19 using an imm