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Trial registered on ANZCTR


Registration number
ACTRN12621001202853
Ethics application status
Approved
Date submitted
31/08/2021
Date registered
9/09/2021
Date last updated
9/09/2021
Date data sharing statement initially provided
9/09/2021
Type of registration
Retrospectively registered

Titles & IDs
Public title
Efficacy of COVID-19 Vaccination in People with Follicular Lymphoma and Waldenström Macroglobulinaemia – A Prospective Cohort Study
Scientific title
Efficacy of COVID-19 Vaccination in People with Follicular Lymphoma and Waldenström Macroglobulinaemia – A Prospective Cohort Study
Secondary ID [1] 305185 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Follicular Lymphoma 323459 0
Waldenstrom Macroglobulinaemia 323460 0
Condition category
Condition code
Blood 321009 321009 0 0
Haematological diseases
Cancer 321057 321057 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Patients with haematological malignancies such as Follicular Lymphoma (FL) and Waldenstrom's Macroglobulinaemia (WM) may have reduced response to the COVID-19 vaccine. This is due to changes in the immune system, either due to the disease itself and their disease treatments (such as chemotherapy). This study aims to assess the immune responses of patients with FL and WM to the COVID-19 vaccine. This study does this by collecting blood samples at defined timepoints:
T1 Baseline (Day of 1st vaccine dose or up to 2 weeks prior).
T2 Post 1st vaccine dose (Day of 2nd dose, or any day a minimum of 21 days post 1st dose).
T3 Post 2nd vaccine dose (28 days +/- 14 days post 2nd dose)
T4 6 months (180 days +/- 30 days post 2nd dose)
T5 12 months following 2nd vaccination (+/- 30 days): this time point is not yet confirmed and will depend on data analysed following T4 and appropriateness for collection.
Intervention code [1] 321583 0
Not applicable
Comparator / control treatment
The comparator/control group are healthy controls that do not have a haematological malignancy.
Control group
Active

Outcomes
Primary outcome [1] 328789 0
Levels of blood IgG anti-spike titres for FL/WM patients treated with immunochemotherapy/BTKi compared to treatment-naïve FL/WM patients and healthy controls.
Timepoint [1] 328789 0
T1. Baseline (Day of 1st vaccine dose or up to 2 weeks prior).
T2. Post 1st vaccine dose (Day of 2nd dose, or any day a minimum of 21 days post 1st dose).
T3. Post 2nd vaccine dose (28 days +/- 14 days post 2nd dose)
T4. 6 months (180 days +/- 30 days post 2nd dose).
T5. 12 months following 2nd vaccination (+/- 30 days): this time point is not yet confirmed and will depend on data analysed following T4 and appropriateness for collection.
Primary outcome [2] 328790 0
Levels of blood antigen-specific T-cell responses for FL patients treated with immunochemotherapy compared to treatment-naïve FL patients and healthy controls.
Timepoint [2] 328790 0
T1. Baseline (Day of 1st vaccine dose or up to 2 weeks prior).
T2. Post 1st vaccine dose (Day of 2nd dose, or any day a minimum of 21 days post 1st dose).
T3. Post 2nd vaccine dose (28 days +/- 14 days post 2nd dose)
T4. 6 months (180 days +/- 30 days post 2nd dose).
T5. 12 months following 2nd vaccination (+/- 30 days): this time point is not yet confirmed and will depend on data analysed following T4 and appropriateness for collection.
Primary outcome [3] 328791 0
Phenotype of blood T-cell response by multi-parameter flow-cytometry for FL/WM patients treated with immunochemotherapy/BTKi compared to treatment-naïve FL/WM patients and healthy controls.
Timepoint [3] 328791 0
T1. Baseline (Day of 1st vaccine dose or up to 2 weeks prior).
T2. Post 1st vaccine dose (Day of 2nd dose, or any day a minimum of 21 days post 1st dose).
T3. Post 2nd vaccine dose (28 days +/- 14 days post 2nd dose)
T4. 6 months (180 days +/- 30 days post 2nd dose).
T5. 12 months following 2nd vaccination (+/- 30 days): this time point is not yet confirmed and will depend on data analysed following T4 and appropriateness for collection.
Secondary outcome [1] 400353 0
Clinical failure of COVID-19 vaccination. Measured as a patient-reported PCR-confirmed SARS-CoV-2 infection and/or clinical diagnosis of COVID-19. Assessment of degree of severity (i.e. managed as: outpatient, non-ICU inpatient care; ICU care; death). Diagnosis will be assessed through patient reported infection and from medical records.
Timepoint [1] 400353 0
T1. Baseline (Day of 1st vaccine dose or up to 2 weeks prior).
T2. Post 1st vaccine dose (Day of 2nd dose, or any day a minimum of 21 days post 1st dose).
T3. Post 2nd vaccine dose (28 days +/- 14 days post 2nd dose)
T4. 6 months (180 days +/- 30 days post 2nd dose).
T5. 12 months following 2nd vaccination (+/- 30 days): this time point is not yet confirmed and will depend on data analysed following T4 and appropriateness for collection.
Secondary outcome [2] 400354 0
Blood baseline antibody and T-cell responses to SARS-CoV-2 coronaviruses.
Timepoint [2] 400354 0
T1. Baseline (Day of 1st vaccine dose or up to 2 weeks prior).
T2. Post 1st vaccine dose (Day of 2nd dose, or any day a minimum of 21 days post 1st dose).
T3. Post 2nd vaccine dose (28 days +/- 14 days post 2nd dose)
T4. 6 months (180 days +/- 30 days post 2nd dose).
T5. 12 months following 2nd vaccination (+/- 30 days): this time point is not yet confirmed and will depend on data analysed following T4 and appropriateness for collection.
Secondary outcome [3] 400355 0
Rates of COVID-19 infection within the FL treated cohort to Pfizer vaccines and Astra Zeneca vaccine or if a mix of both vaccines is delivered to this cohort.
Timepoint [3] 400355 0
T1. Baseline (Day of 1st vaccine dose or up to 2 weeks prior).
T2. Post 1st vaccine dose (Day of 2nd dose, or any day a minimum of 21 days post 1st dose).
T3. Post 2nd vaccine dose (28 days +/- 14 days post 2nd dose)
T4. 6 months (180 days +/- 30 days post 2nd dose).
T5. 12 months following 2nd vaccination (+/- 30 days): this time point is not yet confirmed and will depend on data analysed following T4 and appropriateness for collection.
Secondary outcome [4] 400356 0
Difference in response within the "Phase 3 evaluation of PET-guided, Response-Adapted therapy in patients with previously untreated, high tumour burden follicular lymphoma" (PETReA) treated FL cohorts from the UK to the FL treated cohorts in Australia with our study acting as a validation cohort for the PETReA consortium.
Timepoint [4] 400356 0
T1. Baseline (Day of 1st vaccine dose or up to 2 weeks prior).
T2. Post 1st vaccine dose (Day of 2nd dose, or any day a minimum of 21 days post 1st dose).
T3. Post 2nd vaccine dose (28 days +/- 14 days post 2nd dose)
T4. 6 months (180 days +/- 30 days post 2nd dose).
T5. 12 months following 2nd vaccination (+/- 30 days): this time point is not yet confirmed and will depend on data analysed following T4 and appropriateness for collection.
Secondary outcome [5] 400357 0
Rates of COVID-19 infection within patients with WM cohort to Pfizer vaccines and AstraZeneca vaccine or if a mix of both vaccines is delivered to this cohort.
Timepoint [5] 400357 0
T1. Baseline (Day of 1st vaccine dose or up to 2 weeks prior).
T2. Post 1st vaccine dose (Day of 2nd dose, or any day a minimum of 21 days post 1st dose).
T3. Post 2nd vaccine dose (28 days +/- 14 days post 2nd dose)
T4. 6 months (180 days +/- 30 days post 2nd dose).
T5. 12 months following 2nd vaccination (+/- 30 days): this time point is not yet confirmed and will depend on data analysed following T4 and appropriateness for collection.
Secondary outcome [6] 400358 0
Patient reported differences in any adverse reactions/side effects reported between FL treated and FL treatment-naïve groups.
Timepoint [6] 400358 0
T1. Baseline (Day of 1st vaccine dose or up to 2 weeks prior).
T2. Post 1st vaccine dose (Day of 2nd dose, or any day a minimum of 21 days post 1st dose).
T3. Post 2nd vaccine dose (28 days +/- 14 days post 2nd dose)
T4. 6 months (180 days +/- 30 days post 2nd dose).
T5. 12 months following 2nd vaccination (+/- 30 days): this time point is not yet confirmed and will depend on data analysed following T4 and appropriateness for collection.
Secondary outcome [7] 400359 0
Patient reported differences in any adverse reactions/side effects reported between WM treated and WM treatment-naïve groups.
Timepoint [7] 400359 0
T1. Baseline (Day of 1st vaccine dose or up to 2 weeks prior).
T2. Post 1st vaccine dose (Day of 2nd dose, or any day a minimum of 21 days post 1st dose).
T3. Post 2nd vaccine dose (28 days +/- 14 days post 2nd dose)
T4. 6 months (180 days +/- 30 days post 2nd dose).
T5. 12 months following 2nd vaccination (+/- 30 days): this time point is not yet confirmed and will depend on data analysed following T4 and appropriateness for collection.
Secondary outcome [8] 400730 0
Blood baseline antibody and T-cell responses to seasonal “common cold” coronaviruses.
Timepoint [8] 400730 0
T1. Baseline (Day of 1st vaccine dose or up to 2 weeks prior).
T2. Post 1st vaccine dose (Day of 2nd dose, or any day a minimum of 21 days post 1st dose).
T3. Post 2nd vaccine dose (28 days +/- 14 days post 2nd dose)
T4. 6 months (180 days +/- 30 days post 2nd dose).
T5. 12 months following 2nd vaccination (+/- 30 days): this time point is not yet confirmed and will depend on data analysed following T4 and appropriateness for collection.
Secondary outcome [9] 400731 0
Rates of hospitalisation and death within the FL treated cohort to Pfizer vaccines and Astra Zeneca vaccine or if a mix of both vaccines is delivered to this cohort.
Timepoint [9] 400731 0
T1. Baseline (Day of 1st vaccine dose or up to 2 weeks prior).
T2. Post 1st vaccine dose (Day of 2nd dose, or any day a minimum of 21 days post 1st dose).
T3. Post 2nd vaccine dose (28 days +/- 14 days post 2nd dose)
T4. 6 months (180 days +/- 30 days post 2nd dose).
T5. 12 months following 2nd vaccination (+/- 30 days): this time point is not yet confirmed and will depend on data analysed following T4 and appropriateness for collection.
Secondary outcome [10] 400733 0
Rates of hospitalisation and death within the WM treated cohort to Pfizer vaccines and Astra Zeneca vaccine or if a mix of both vaccines is delivered to this cohort.
Timepoint [10] 400733 0
T1. Baseline (Day of 1st vaccine dose or up to 2 weeks prior).
T2. Post 1st vaccine dose (Day of 2nd dose, or any day a minimum of 21 days post 1st dose).
T3. Post 2nd vaccine dose (28 days +/- 14 days post 2nd dose)
T4. 6 months (180 days +/- 30 days post 2nd dose).
T5. 12 months following 2nd vaccination (+/- 30 days): this time point is not yet confirmed and will depend on data analysed following T4 and appropriateness for collection.

Eligibility
Key inclusion criteria
1. Patient with low grade FL treated with immunochemotherapy
2. Patients with FL who are treatment-naïve.
3. Patients with WM currently on treatment with a BTKi
4. Patients with WM during or following treatment with standard immunochemotherapy
5. Patients with WM who are treatment-naïve.
6. A group of healthy volunteers who are controls
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Patients with additional medical co-morbidities and/or medications that compromise their immune function (e.g. inflammatory bowel disease, rheumatoid arthritis, SLE, HIV, high dose prednisolone for reasons other than lymphoma treatment). If there is any doubt, the final decision will rest with the PI.
2. Those not wishing to consent

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
The Head of Biostatistics at the Kirby Institute, Prof Matthew Law, has determined the minimum numbers needed to detect a 4 fold decreased in anti-spike Ab (compared with healthy volunteers) following COVID-19 vaccinations. These data are based on the original published licensing data for both the Pfizer and AstraZeneca vaccines. For the Pfizer vaccine the estimate is n=4 for both cohort and healthy controls to determine a 4-fold decreased with 80% power. For the AstraZeneca vaccine it is n=7 for both cohort group and healthy controls. Therefore given the robustness of the published data we are confident of detecting significantly lower Ab titres as proposed.

Descriptive statistics of continuous data will be based on means (standard deviation) or median (interquartile range) depending on data normality. Categorical data will be summarised using frequency distributions. Differences between groups (anti-SARS-CoV-2 antibodies, Neutralising Ab test and Antigen-specific T cell responses) will be determined by the non-parametric Mann-Whitney tests.

Analyses of the outcomes will adhere to the Intention to Treat (ITT) principle, where all participants will be included unless specified otherwise. Analysis of endpoints will be according to cohort. p-values will be considered significant if <0.05.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
18/05/2021
Date of last participant enrolment
Anticipated
Actual
16/06/2021
Date of last data collection
Anticipated
30/06/2022
Actual
Sample size
Target
80
Accrual to date
Final
85
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 20440 0
Concord Repatriation Hospital - Concord
Recruitment postcode(s) [1] 35209 0
2139 - Concord

Funding & Sponsors
Funding source category [1] 309569 0
Hospital
Name [1] 309569 0
Department of Haematology, Concord Repatriation General Hospital
Country [1] 309569 0
Australia
Funding source category [2] 309572 0
Charities/Societies/Foundations
Name [2] 309572 0
International Waldenstrom's Macroglobulinaemia Foundation (IWMF)
Country [2] 309572 0
United States of America
Primary sponsor type
Hospital
Name
Concord Repatriation General Hospital
Address
Dept of Haematology, Concord Hospital
Ground East, Main Building
1 Hospital Rd, Concord NSW 2139
Country
Australia
Secondary sponsor category [1] 310575 0
None
Name [1] 310575 0
Address [1] 310575 0
Country [1] 310575 0
Other collaborator category [1] 281966 0
University
Name [1] 281966 0
The Kirby Institute, The University of New South Wales
Address [1] 281966 0
Level 5 The Kirby Institute
Wallace Wurth Building
UNSW, Kensington NSW 2033
Country [1] 281966 0
Australia
Other collaborator category [2] 281968 0
Charities/Societies/Foundations
Name [2] 281968 0
WMozzies
Address [2] 281968 0
30 Coasters Retreat
Coasters Retreat, NSW, 2108
Country [2] 281968 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309347 0
Sydney Local Health District HREC
Ethics committee address [1] 309347 0
Ethics committee country [1] 309347 0
Australia
Date submitted for ethics approval [1] 309347 0
01/05/2021
Approval date [1] 309347 0
07/05/2021
Ethics approval number [1] 309347 0
X21-0120

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 113854 0
Dr Brendan Beaton
Address 113854 0
Department of Haematology,
Ground East, Main Building
Concord Hospital
1 Hospital Road, Concord, NSW, Australia, 2139
Country 113854 0
Australia
Phone 113854 0
+61 2 9767 5765
Fax 113854 0
Email 113854 0
brendan.beaton1@health.nsw.gov.au
Contact person for public queries
Name 113855 0
Judith Trotman
Address 113855 0
Department of Haematology,
Ground East, Main Building
Concord Hospital
1 Hospital Road, Concord, NSW, Australia, 2139
Country 113855 0
Australia
Phone 113855 0
+61 2 9767 7243
Fax 113855 0
Email 113855 0
judith.trotman@health.nsw.gov.au
Contact person for scientific queries
Name 113856 0
Judith Trotman
Address 113856 0
Department of Haematology,
Ground East, Main Building
Concord Hospital
1 Hospital Road, Concord, NSW, Australia, 2139
Country 113856 0
Australia
Phone 113856 0
+61 2 9767 7243
Fax 113856 0
Email 113856 0
judith.trotman@health.nsw.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.