Chronic lymphocytic leukaemia Cancer
Conditions
Interventions
The intervention is a 3-week temporary pause (suspension) of existing ongoing BTKi therapy. The 3-week temporary pause starts 1 week before vaccination 6 days of no BTKi administration, then on day 7
Sponsors
University of Birmingham
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Aged 18 years and over 2. Confirmed diagnosis of chronic lymphocytic leukaemia 3. Taking oral NICE-approved BTKi therapy (Acalabrutinib or Ibrutinib) for at least 12 months since the date of initiation of therapy 4. Has achieved complete remission (CR; including CR with incomplete marrow recovery), partial remission (PR; including nodular PR or PR with lymphocytosis) or stable disease by the International Workshop on CLL (iwCLL) response criteria 5. Considered able to temporarily pause (suspend) BTKi therapy for three weeks without the risk of a substantial increase in disease activity 6. Anticipated to take BTKi over the next 4 months (i.e. not in the STATIC trial arm where therapy is stopped) 7. Willing to accept either study arm allocation 8. Able to give informed consent 9. Eligible for a planned vaccination for COVID-19
Exclusion criteria
Exclusion criteria: 1. Insufficient time for applying the intervention prior to the planned COVID-19 vaccination. 2. Diagnosed with alternative conditions requiring treatment with BTKi 3. Treated with anti-CD20 antibody therapy in the last 18 months or planning to start it 4. Concurrent immune suppressive treatments in the last 3 months specifically: methotrexate, ciclosporin, BCL-2 inhibitors, azathioprine, mycophenolate, prednisolone, biologic agents 5. Any contraindication to COVID-19 vaccination 6. Richter’s transformation requiring active therapy 7. Radiotherapy or cancer chemotherapy in the last 6 months 8. Active solid organ cancer (people with skin cancer or those cured of solid organ cancer are eligible) 9. Receiving or has received in the past 6 months immunoglobulin replacement therapy 10. Receiving or has received in the past 6 months monoclonal antibody against COVID-19 spike protein
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Anti-SARS-CoV-2 spike (S) protein receptor binding domain (RBD) antibody levels measured using Roche Elecsys® electrochemiluminescence assay (Roche S) at baseline and at 3 weeks post-SARS-CoV-2 vaccination | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Anti-spike (IgG, IgA and IgM) RBD antibody levels measured using Roche Elecsys® electrochemiluminescence assay (Roche S) at baseline and at 12 weeks post-SARS-CoV-2 vaccination 2. Neutralising antibody titre levels at 50% and 90% against Wuhan D614G (B.1) and the current variant of concern (VOC) ) will be assessed using validated laboratory methods at baseline, 3 and 12 weeks post SARS-CoV-2 vaccination 3. Antigen-specific T-cell response for ancestral Wuhan and 1 x VOC spike, and combined nucleocapsid and membrane response measured using the enzyme-linked immunosorbent spot (ELISpot) assay at baseline and 3 weeks post-SARS-CoV-2 vaccination 4. Antibody response to 4 strains of influenza present in the Autumn 22 vaccine (continuous OD 450nm read out) measured using ELISA [For those who receive flu vaccination only] at baseline and 3 weeks post SARS-CoV-2 vaccination 5. Disease activity questions (raised temperature, enlarged or new lymph nodes) measured using a non-validated questionnaire answered by participants electronically at baseline, 3 and 12 weeks post-SARS-CoV-2 vaccination or a participant attending their 3-week clinic visit – if the adherence questions have not been completed they will be asked to complete the questions at that visit 6. Full Blood Count (Haemoglobin, platelet levels and lymphocyte levels) measured using standard medical laboratory methods at baseline, 3 and 12 weeks post SARS-CoV-2 vaccination 7. Blood Film (presence of new prolymphocytes, smear cells or lymphocytosis) measured using standard medical laboratory methods at baseline, 3 and 12 weeks post SARS-CoV-2 vaccination 8. Lactate dehydrogenase levels measured using standard medical laboratory methods at baseline, 3 and 12 weeks post SARS-CoV-2 vaccination 9. Health-related quality of life (HRQoL) measured using the EORTC-QLQ-CLL17 scales (symptom burden, physical condition/fatigue, and worries/fears on health and functioning) at baseline, 3 and 12 weeks post-SARS-CoV-2 vaccinat | — |
Countries
England, United Kingdom
Contacts
Public ContactVicki Barber
Outcome results
None listed