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

NCT ID: NCT04534725

Last Updated: 2023-08-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 441 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-17
• Study Completion Date: 2023-04-19

Brief 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.

ARM 1 is evaluating the effect of interferon-alpha (vs placebo) on the incidence of COVID-19 infection in cancer patients with no COVID-19 infection or no known COVID-19 positive contacts.

ARM 2 is evaluating the effect of interferon-alpha (vs placebo) on the incidence of COVID-19 infection in cancer patients with confirmed exposure to COVID-19 virus.

ARM 3 is evaluating the effect of Selinexor (vs placebo) on the incidence of COVID-19 infection in cancer patients with moderate COVID-19 infection.

ARM 4 is evaluating the effect of Lenzilumab (vs placebo) on the treatment of COVID-19 infection in cancer patients with severe COVID-19 infection.

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.

Conditions

Cancer; Covid19; Respiratory Viral Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

prophylaxis

This study arm (arm 1) is evaluating the effect of interferon-alpha on the incidence of COVID-19 infection in cancer patients with no COVID-19 infection or no known COVID-19 positive contacts.

Participants in this study arm are randomly allocated (by chance) to one of two groups. One group will receive daily interferon-alpha intranasal spray for 3 months while the other group will receive a daily placebo intranasal spray for 3 months.

Participants will be followed during the 3-month treatment for incidence of COVID-19 and other respiratory infections.

Group Type: EXPERIMENTAL

Interferon alfa

Intervention Type: DRUG

intranasal spray

Post-Exposure Prophylaxis

This study arm (arm 2) is evaluating the effect of interferon-alpha on the incidence of COVID-19 infection in cancer patients with confirmed exposure to COVID-19 virus.

Participants in this study arm are randomly allocated (by chance) to one of two groups. One group will receive daily interferon-alpha intranasal spray for 7 days (at a higher dose than arm 1) while the other group will receive a daily placebo intranasal spray for 7 days

Participants will be followed for 28 days for incidence of COVID-19 and other respiratory infections.

Group Type: EXPERIMENTAL

Interferon alfa

Intervention Type: DRUG

intranasal spray

Moderate COVID-19 infection

This study arm (arm 3) is evaluating the effect of Selinexor on the incidence of COVID-19 infection in cancer patients with moderate COVID-19 infection.

Participants in this study arm are randomly allocated (by chance) to one of two groups. One group will receive oral Selinexor 3 times a week for 2 weeks while the other group will receive oral placebo 3 times a week for 2 weeks

Participants will be followed for 60 days to assess effectiveness and safety.

Group Type: EXPERIMENTAL

Selinexor

Intervention Type: DRUG

oral tablet

Severe COVID-19 infection

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.

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.

Group Type: EXPERIMENTAL

Lenzilumab

Intervention Type: DRUG

intravenous infusion

Interventions

Interferon alfa

intranasal spray

Intervention Type: DRUG

Selinexor

oral tablet

Intervention Type: DRUG

Lenzilumab

intravenous infusion

Intervention Type: DRUG

Eligibility Criteria

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

1. Age equal to or greater than 18 years old.

2. Any haematological or solid tumour

3. Signed written and verbal informed consent

4. Have been exposed to a known COVID-19 case within the last 72 hours, defined by the current Department of Health and Human services such as household contact, 15 minutes of face to face exposure, 2 hours in close space.

5. Willingness to inform the study nurse/co-ordinator of COVID-19 testing

6. 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 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 5. Laboratory confirmation of SARS-CoV-2 by PCR as per local laboratory assays 6. Hospitalised 7. Symptoms of COVID-19 such as:

1. Fever equal to or greater than 38 degrees Celsius OR

2. Tachypnoea respiratory rate equal to or greater than 20 breaths/min OR

3. Pulse Oxygen saturation (SpO2) equal to or less than 94% 8. Concurrent standard of care antimicrobials, antivirals are allowed. 9. Female and male patients of child bearing potential will use highly effective contraception. In female child bearing potential participants a negative urine pregnancy test will be required.

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 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.

9. 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 Criteria

• ARM 1

1. Previous diagnosis of COVID-19 (microbiologically proven, either symptomatic or asymptomatic)

2. Have been exposed to a known COVID-19 case within the last 72 hours, defined by the current Department of Health and Human services such as household contact, 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 bleeding requiring intervention, nasal malignancy, nasal deformity, radiotherapy to the nasopharynx and/or oropharynx

4. Pregnant or breast-feeding women, or women who wish to become pregnant during 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 prevention of COVID-19

8. Currently unwell with influenza-like symptoms - if participant is found to be COVID-19 negative and becomes asymptomatic, they can be reconsidered for participation

ARM 2

1. Previous diagnosis of COVID-19 (microbiologically proven, either symptomatic or asymptomatic)

2. Any contra-indication to intra-nasal IFN-a such as severe nasal bleeding requiring intervention, nasal malignancy, nasal deformity, radiotherapy to the nasopharynx and/or oropharynx

3. Pregnant or breast-feeding women, or women who wish to become pregnant during the course of the study

4. Patient unable to return for follow-up

5. Life expectancy of less than 1 month

6. Patient already included in another intervention study on the prevention of COVID-19

7. Currently unwell with influenza-like symptoms

ARM 3

1. Unable to take oral medication

2. Any known allergic reactions to selinexor or concomitant medication-related contra-indications to selinexor.

3. Severe critical COVID-19 infection defined as:

1. Requiring invasive or non-invasive mechanical ventilation, ECMO

2. Anticipated unlikely to survive within 48 hours

4. In the opinion of the investigator and primary oncologist, participation in the study would not be in the best interests of the participant

5. Severe renal impairment defined as creatinine clearance (CrCL) < 20ml/min as calculated using the Cockcroft Gault formula

6. Severe hepatic impairment defined as aspartate transaminase (AST) or alanine transaminase (ALT) > 5 x upper limit of normal (ULN)

ARM 4

1. Invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) 2. History of pulmonary alveolar proteinosis (PAP). 3. Women of childbearing potential who are pregnant or breastfeeding. 4. Known hypersensitivity to lenzilumab or any of its components. 5 .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.

6. Use of GM-CSF agents (e.g., sargramostim) within 8 weeks prior to randomisation.

7. 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 and efficacy of the study treatment or puts the subject at unacceptably high risk from the study.

9. Participation in another interventional study of COVID-19

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peter MacCallum Cancer Centre, Australia

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Westmead Hospital

Westmead, New South Wales, Australia

St Vincent's Hospital

Fitzroy, Victoria, Australia

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Royal Melbourne Hospital

Melbourne, Victoria, Australia

Austin Health

Melbourne, Victoria, Australia

Countries

Australia

References

Yong MK, Thursky K, Crane M, Spelman T, Mahar RK, Simpson JA, Scott AM, Harrison SJ, Szer J, Pellegrini M, Lingaratnam S, Pang KC, Tennakoon S, Sim BZ, Blyth E, Gan HK, Quach H, McIntosh MP, Page H, Woolstencroft R, Slavin M. Interferon-alpha Nasal Spray Prophylaxis Reduces COVID-19 in Cancer Patients: A Randomized, Double-Blinded, Placebo-Controlled Trial. Clin Infect Dis. 2025 Aug 28:ciaf409. doi: 10.1093/cid/ciaf409. Online ahead of print.

Reference Type: DERIVED

PMID: 40874769 (View on PubMed)

Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.

Reference Type: DERIVED

PMID: 34473343 (View on PubMed)

Other Identifiers

Peter Mac ID 20/135

Identifier Type: -

Identifier Source: org_study_id