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

NCT04534725 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: Peter Mac ID 20/135
• Study Type: interventional
• Target: 441
• Locations: 1 country
• Sites: 5

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

Keywords

COVID-19; cancer

Outcome Measures

Primary Outcomes (6)

• Incidence of COVID-19 in cancer patients using interferon-alpha as prophylaxis without known positive contact with COVID-19 (COVID-19 confirmed by qPCR from respiratory swab)

  Incidence of COVID-19 in cancer patients using interferon-alpha as prophylaxis without known positive contact with COVID-19 (COVID-19 confirmed by qPCR from respiratory swab)

  3 months from baseline.

• incidence of any upper or lower community acquired respiratory viral infection assessed using local standard of care testing

  incidence of any upper or lower community acquired respiratory viral infection (define as identification of respiratory viruses such as coronavirus other than SARS-CoV-2, influenza, parainfluenza, respiratory syncytial virus, rhinovirus, adenovirus, human metapneumovirus). assessed using local standard of care testing (e.g. respiratory swabs, saliva and/or blood)

  3 months from baseline.

• incidence of COVID-19 when Interferon alpha is given as post-exposure prophylaxis with a known positive contact or exposure with COVID-19. COVID-19 confirmed by qPCR from respiratory swab .

  incidence of COVID-19 when Interferon alpha is given as post-exposure prophylaxis with a known positive contact or exposure with COVID-19. COVID-19 confirmed by qPCR from respiratory swab .

  28 days from baseline

• incidence of any upper or lower community acquired respiratory viral infection assessed using local standard of care testing

  incidence of any upper or lower community acquired respiratory viral infection (define as identification of respiratory viruses such as coronavirus other than SARS-CoV-2, influenza, parainfluenza, respiratory syncytial virus, rhinovirus, adenovirus, human metapneumovirus). Assessed using local standard of care testing (e.g. respiratory swabs, saliva and/or blood)

  28 days from baseline

• incidence of death and/or need for invasive or non-invasive ventilation. assessed using medical records

  composite outcome: incidence of death and/or need for invasive or non-invasive ventilation. assessed using medical records

  60 days from baseline

• time to clinical improvement or discharge from hospital assessed using medical records

  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 Outcomes (46)

• ARM 1: Duration of acute respiratory/ILI symptoms in case of confirmed respiratory infection during the study period. Assessed using patient symptom Diary PRO tool

  120 days from baseline

• ARM 1: Time to diagnosis of COVID-19 in case of confirmed COVID-19 diagnosed during the study period (days). Assessed using patient medical records

  120 days from baseline

• ARM 1: Time to diagnosis of other respiratory viral infection in case of confirmed other respiratory viral infection diagnosed during the study period (days). assessed using patient medical records

  120 days from baseline

• ARM 1: Illness severity in case of confirmed COVID-19 diagnosed during the study period using WHO clinical progression scale

  120 days from baseline

• ARM 1: Incidence of unplanned all-cause hospital admission during the study period. assessed using medical records

  120 days from baseline

Study Arms (4)

prophylaxis

EXPERIMENTAL

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.

Drug: Interferon alfa

Post-Exposure Prophylaxis

EXPERIMENTAL

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.

Drug: Interferon alfa

Moderate COVID-19 infection

EXPERIMENTAL

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.

Drug: Selinexor

Severe COVID-19 infection

EXPERIMENTAL

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.

Drug: Lenzilumab

Interventions

Interferon alfa DRUG

intranasal spray

Post-Exposure Prophylaxis; prophylaxis

Selinexor DRUG

oral tablet

Moderate COVID-19 infection

Lenzilumab DRUG

intravenous infusion

Severe COVID-19 infection

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ARM 1:
• Age equal to or greater than 18 years old
• Any haematological or solid tumour
• Signed written and verbal informed consent
• Willingness to inform the study nurse/co-ordinator of COVID-19 testing
• Willingness to perform a self-collect nose/throat swab
• ARM 2
• Age equal to or greater than 18 years old.
• Any haematological or solid tumour
• Signed written and verbal informed consent
• 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.
• Willingness to inform the study nurse/co-ordinator of COVID-19 testing
• 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:
• Fever equal to or greater than 38 degrees Celsius OR

You may not qualify if:

• ARM 1
• Previous diagnosis of COVID-19 (microbiologically proven, either symptomatic or asymptomatic)
• 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.
• 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
• Pregnant or breast-feeding women, or women who wish to become pregnant during the course of the study
• Participant unable to return for regular follow-up
• Life expectancy of less than 4 months
• Participant already included in another intervention study on the prevention of COVID-19
• 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
• Previous diagnosis of COVID-19 (microbiologically proven, either symptomatic or asymptomatic)
• 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
• Pregnant or breast-feeding women, or women who wish to become pregnant during the course of the study
• Patient unable to return for follow-up
• Life expectancy of less than 1 month

Sponsors & Collaborators

• Peter MacCallum Cancer Centre, Australia: lead

Study Sites (5)

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

St Vincent's Hospital

Fitzroy, Victoria, 3065, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Royal Melbourne Hospital

Melbourne, Victoria, 3052, Australia

Location

Austin Health

Melbourne, Victoria, 3084, Australia

Location

Related Publications (2)

• 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.

  PMID: 40874769 DERIVED

• 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.

  PMID: 34473343 DERIVED

MeSH Terms

Conditions

Neoplasms; COVID-19

Interventions

Interferon-alpha; selinexor; lenzilumab

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: double blinding from central system.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: the study uses a SMART design. (sequential multiple arm randomised trial) meaning that participants can enter into the study and progress through the subsequent arms if they meet the additional eligibility criteria (for instance, pre-covid \> post exposure \> develop moderate infection \> infection becomes severe) it is important to note that participants can enter into the study at any point and do not have to transition into the other arms

Study Record Dates

• First Submitted: August 30, 2020
• First Posted: September 1, 2020
• Study Start: December 17, 2020
• Primary Completion: November 28, 2022
• Study Completion: April 19, 2023
• Last Updated: August 24, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

AU (5)