Protocol for a multicentre randomised controlled trial examining the effects of temporarily pausing Bruton tyrosine kinase inhibitor therapy to coincide with SARS-CoV-2 vaccination and its impact on immune responses in patients with chronic lymphocytic leukaemia

Vicki S Barber; Nicholas Peckham; Lelia Duley; Anne Francis; Abhishek Abhishek; Paul Moss; Jonathan A Cook; Helen M Parry

doi:10.1136/bmjopen-2023-077946

Protocol for a multicentre randomised controlled trial examining the effects of temporarily pausing Bruton tyrosine kinase inhibitor therapy to coincide with SARS-CoV-2 vaccination and its impact on immune responses in patients with chronic lymphocytic leukaemia

Vicki S Barber, Nicholas Peckham, Lelia Duley, Anne Francis, Abhishek Abhishek, Paul Moss, Jonathan A Cook, Helen M Parry^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

8 Downloads (Pure)

Abstract

INTRODUCTION: People who are immunocompromised have a poor biological response to vaccinations. This study aims to determine in patients with chronic lymphocytic leukaemia (CLL) if a 3-week pause in Bruton tyrosine kinase inhibitor therapy (BTKi) starting 1 week before delivery of SARS-CoV-2 vaccine booster, improves vaccine immune response when compared with continuation of BTKi.

METHODS AND ANALYSIS: An open-label, randomised controlled superiority trial will be conducted in haematology clinics in approximately 10 UK National Health Service (NHS) hospitals. The sample size is 120, randomised 1:1 to intervention and usual care arms. The primary outcome is anti-spike-receptor binding domain (RBD) antibody level at 3 weeks post-SARS-CoV-2 booster vaccination. Secondary outcomes are RBD antibody levels at 12 weeks postbooster vaccination, participant global assessments of disease activity, blood films, full blood count and lactate dehydrogenase levels, impact on quality of life, self-reported adherence with request to temporarily pause or continue BTKi, T cell response against spike protein and relative neutralising antibody titre against SARS-CoV-2 viral variants. Additionally, there will be an investigation of any effects in those given influenza vaccination contemporaneously versus COVID-19 alone.The primary analysis will be performed on the as randomised groups ('intention to treat'). The difference between the study arms in anti-spike-RBD antibody level will be estimated using a mixed effects regression model, allowing for repeated measures clustered within participants. The model will be adjusted for randomisation factor (first line or subsequent line of therapy), and prior infection status obtained from prerandomisation antinucleocapsid antibodies as fixed effects.

ETHICS AND DISSEMINATION: This study has been approved by Leeds East Research Ethics Committee and Health Research Authority (REC Reference:22/YH/0226, IRAS ID: 319057). Dissemination will be via peer-review publications, newsletters and conferences. Results will be communicated to participants, the CLL patient and clinical communities and health policy-makers.

TRIAL REGISTRATION NUMBER: ISRCTN14197181.

Original language	English
Article number	e077946
Journal	BMJ open
Volume	13
Issue number	9
DOIs	https://doi.org/10.1136/bmjopen-2023-077946
Publication status	Published - 28 Sept 2023

Bibliographical note

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1136/bmjopen-2023-077946Licence: Creative Commons: Attribution (CC BY)

BarberVS2023ProtocolFinal published version, 1.1 MBLicence: Creative Commons: Attribution (CC BY)

Fingerprint

Dive into the research topics of 'Protocol for a multicentre randomised controlled trial examining the effects of temporarily pausing Bruton tyrosine kinase inhibitor therapy to coincide with SARS-CoV-2 vaccination and its impact on immune responses in patients with chronic lymphocytic leukaemia'. Together they form a unique fingerprint.

Cite this

Barber, V. S., Peckham, N., Duley, L., Francis, A., Abhishek, A., Moss, P., Cook, J. A., & Parry, H. M. (2023). Protocol for a multicentre randomised controlled trial examining the effects of temporarily pausing Bruton tyrosine kinase inhibitor therapy to coincide with SARS-CoV-2 vaccination and its impact on immune responses in patients with chronic lymphocytic leukaemia. BMJ open, 13(9), Article e077946. https://doi.org/10.1136/bmjopen-2023-077946

@article{baff3a18e86b4e0e82e164b007c67759,

title = "Protocol for a multicentre randomised controlled trial examining the effects of temporarily pausing Bruton tyrosine kinase inhibitor therapy to coincide with SARS-CoV-2 vaccination and its impact on immune responses in patients with chronic lymphocytic leukaemia",

abstract = "INTRODUCTION: People who are immunocompromised have a poor biological response to vaccinations. This study aims to determine in patients with chronic lymphocytic leukaemia (CLL) if a 3-week pause in Bruton tyrosine kinase inhibitor therapy (BTKi) starting 1 week before delivery of SARS-CoV-2 vaccine booster, improves vaccine immune response when compared with continuation of BTKi.METHODS AND ANALYSIS: An open-label, randomised controlled superiority trial will be conducted in haematology clinics in approximately 10 UK National Health Service (NHS) hospitals. The sample size is 120, randomised 1:1 to intervention and usual care arms. The primary outcome is anti-spike-receptor binding domain (RBD) antibody level at 3 weeks post-SARS-CoV-2 booster vaccination. Secondary outcomes are RBD antibody levels at 12 weeks postbooster vaccination, participant global assessments of disease activity, blood films, full blood count and lactate dehydrogenase levels, impact on quality of life, self-reported adherence with request to temporarily pause or continue BTKi, T cell response against spike protein and relative neutralising antibody titre against SARS-CoV-2 viral variants. Additionally, there will be an investigation of any effects in those given influenza vaccination contemporaneously versus COVID-19 alone.The primary analysis will be performed on the as randomised groups ('intention to treat'). The difference between the study arms in anti-spike-RBD antibody level will be estimated using a mixed effects regression model, allowing for repeated measures clustered within participants. The model will be adjusted for randomisation factor (first line or subsequent line of therapy), and prior infection status obtained from prerandomisation antinucleocapsid antibodies as fixed effects.ETHICS AND DISSEMINATION: This study has been approved by Leeds East Research Ethics Committee and Health Research Authority (REC Reference:22/YH/0226, IRAS ID: 319057). Dissemination will be via peer-review publications, newsletters and conferences. Results will be communicated to participants, the CLL patient and clinical communities and health policy-makers.TRIAL REGISTRATION NUMBER: ISRCTN14197181.",

author = "Barber, {Vicki S} and Nicholas Peckham and Lelia Duley and Anne Francis and Abhishek Abhishek and Paul Moss and Cook, {Jonathan A} and Parry, {Helen M}",

note = "{\textcopyright} Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.",

year = "2023",

month = sep,

day = "28",

doi = "10.1136/bmjopen-2023-077946",

language = "English",

volume = "13",

journal = "BMJ open",

issn = "2044-6055",

publisher = "BMJ Publishing Group",

number = "9",

}

Barber, VS, Peckham, N, Duley, L, Francis, A, Abhishek, A, Moss, P, Cook, JA & Parry, HM 2023, 'Protocol for a multicentre randomised controlled trial examining the effects of temporarily pausing Bruton tyrosine kinase inhibitor therapy to coincide with SARS-CoV-2 vaccination and its impact on immune responses in patients with chronic lymphocytic leukaemia', BMJ open, vol. 13, no. 9, e077946. https://doi.org/10.1136/bmjopen-2023-077946

Protocol for a multicentre randomised controlled trial examining the effects of temporarily pausing Bruton tyrosine kinase inhibitor therapy to coincide with SARS-CoV-2 vaccination and its impact on immune responses in patients with chronic lymphocytic leukaemia. / Barber, Vicki S; Peckham, Nicholas; Duley, Lelia et al.
In: BMJ open, Vol. 13, No. 9, e077946, 28.09.2023.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Protocol for a multicentre randomised controlled trial examining the effects of temporarily pausing Bruton tyrosine kinase inhibitor therapy to coincide with SARS-CoV-2 vaccination and its impact on immune responses in patients with chronic lymphocytic leukaemia

AU - Barber, Vicki S

AU - Peckham, Nicholas

AU - Duley, Lelia

AU - Francis, Anne

AU - Abhishek, Abhishek

AU - Moss, Paul

AU - Cook, Jonathan A

AU - Parry, Helen M

PY - 2023/9/28

Y1 - 2023/9/28

N2 - INTRODUCTION: People who are immunocompromised have a poor biological response to vaccinations. This study aims to determine in patients with chronic lymphocytic leukaemia (CLL) if a 3-week pause in Bruton tyrosine kinase inhibitor therapy (BTKi) starting 1 week before delivery of SARS-CoV-2 vaccine booster, improves vaccine immune response when compared with continuation of BTKi.METHODS AND ANALYSIS: An open-label, randomised controlled superiority trial will be conducted in haematology clinics in approximately 10 UK National Health Service (NHS) hospitals. The sample size is 120, randomised 1:1 to intervention and usual care arms. The primary outcome is anti-spike-receptor binding domain (RBD) antibody level at 3 weeks post-SARS-CoV-2 booster vaccination. Secondary outcomes are RBD antibody levels at 12 weeks postbooster vaccination, participant global assessments of disease activity, blood films, full blood count and lactate dehydrogenase levels, impact on quality of life, self-reported adherence with request to temporarily pause or continue BTKi, T cell response against spike protein and relative neutralising antibody titre against SARS-CoV-2 viral variants. Additionally, there will be an investigation of any effects in those given influenza vaccination contemporaneously versus COVID-19 alone.The primary analysis will be performed on the as randomised groups ('intention to treat'). The difference between the study arms in anti-spike-RBD antibody level will be estimated using a mixed effects regression model, allowing for repeated measures clustered within participants. The model will be adjusted for randomisation factor (first line or subsequent line of therapy), and prior infection status obtained from prerandomisation antinucleocapsid antibodies as fixed effects.ETHICS AND DISSEMINATION: This study has been approved by Leeds East Research Ethics Committee and Health Research Authority (REC Reference:22/YH/0226, IRAS ID: 319057). Dissemination will be via peer-review publications, newsletters and conferences. Results will be communicated to participants, the CLL patient and clinical communities and health policy-makers.TRIAL REGISTRATION NUMBER: ISRCTN14197181.

AB - INTRODUCTION: People who are immunocompromised have a poor biological response to vaccinations. This study aims to determine in patients with chronic lymphocytic leukaemia (CLL) if a 3-week pause in Bruton tyrosine kinase inhibitor therapy (BTKi) starting 1 week before delivery of SARS-CoV-2 vaccine booster, improves vaccine immune response when compared with continuation of BTKi.METHODS AND ANALYSIS: An open-label, randomised controlled superiority trial will be conducted in haematology clinics in approximately 10 UK National Health Service (NHS) hospitals. The sample size is 120, randomised 1:1 to intervention and usual care arms. The primary outcome is anti-spike-receptor binding domain (RBD) antibody level at 3 weeks post-SARS-CoV-2 booster vaccination. Secondary outcomes are RBD antibody levels at 12 weeks postbooster vaccination, participant global assessments of disease activity, blood films, full blood count and lactate dehydrogenase levels, impact on quality of life, self-reported adherence with request to temporarily pause or continue BTKi, T cell response against spike protein and relative neutralising antibody titre against SARS-CoV-2 viral variants. Additionally, there will be an investigation of any effects in those given influenza vaccination contemporaneously versus COVID-19 alone.The primary analysis will be performed on the as randomised groups ('intention to treat'). The difference between the study arms in anti-spike-RBD antibody level will be estimated using a mixed effects regression model, allowing for repeated measures clustered within participants. The model will be adjusted for randomisation factor (first line or subsequent line of therapy), and prior infection status obtained from prerandomisation antinucleocapsid antibodies as fixed effects.ETHICS AND DISSEMINATION: This study has been approved by Leeds East Research Ethics Committee and Health Research Authority (REC Reference:22/YH/0226, IRAS ID: 319057). Dissemination will be via peer-review publications, newsletters and conferences. Results will be communicated to participants, the CLL patient and clinical communities and health policy-makers.TRIAL REGISTRATION NUMBER: ISRCTN14197181.

U2 - 10.1136/bmjopen-2023-077946

DO - 10.1136/bmjopen-2023-077946

M3 - Article

C2 - 37770269

SN - 2044-6055

VL - 13

JO - BMJ open

JF - BMJ open

IS - 9

M1 - e077946

ER -

Barber VS, Peckham N, Duley L, Francis A, Abhishek A, Moss P et al. Protocol for a multicentre randomised controlled trial examining the effects of temporarily pausing Bruton tyrosine kinase inhibitor therapy to coincide with SARS-CoV-2 vaccination and its impact on immune responses in patients with chronic lymphocytic leukaemia. BMJ open. 2023 Sept 28;13(9):e077946. doi: 10.1136/bmjopen-2023-077946