Covid-19 Vaccine Response in Immunocompromised Haematology Patients

Study Overview
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Brief Summary
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The UK Medicine and Healthcare products Regulatory Agency (MHRA) granted temporary authorisation to three Covid-19 vaccines in December 2020 and January 2021. These vaccinations include: Covid-19 mRNA BNT162b2 vaccine (Pfizer-BioNtech vaccine); ChAdOx1-S vaccine (Astra Zeneca vaccine); Covid-19 mRNA vaccine (Moderna vaccine). Any other Covid-19 vaccines approved for use by the MHRA in immunocompromised and immunocompetent patients are to be included in this study. The above vaccines have received temporary authorisation after placebo-controlled phase 3 studies confirmed their safety and efficacy in over 100,000 volunteers. People who were immunocompromised or were receiving chemotherapy, radiotherapy or immunoglobulin treatment were excluded from these studies. Safety, efficacy, and durability of antibody response in these studies has been assessed for up to 14 weeks only. These vaccines are being rolled out in the UK and have been recommended for use for immunosuppressed individuals including patients undergoing chemotherapy, immunotherapy, radiotherapy, and those who have undergone stem cell transplantation. Though the MHRA has approved vaccination for immunocompromised patients there is no published evidence to confirm safety and efficacy in these patients. The durability of antibody response and whether this is affected by concurrent chemotherapy, immunotherapy, radiotherapy treatment is also unknown. This observational study aims to evaluate the immune response to Covid-19 vaccines in haematology patients who have immune suppression either due to disease, treatment, or both. The investigators plan to measure Anti-SARS-COV2 IgG antibody levels at 3-5 time points 30 days apart after patients have received their 2nd dose of Covid-19 vaccine. The investigators will also collect any adverse events reported by patient including Covid-19 infection or disease after vaccination. The study plans to recruit 50 haematology patients who are clinically assessed by a haematologist as immunosuppressed due to their disease, treatment, or both. The study also plans to recruit 30 healthy (immunocompetent) volunteers who would be the control group for comparison of antibody response and durability.

Official Title
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A Single-centre, Observational Study to Evaluate Immune Response to Covid-19 Vaccines in Immunocompromised Patients With Haematological Disorders

Conditions
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Covid19, Haematological Disorders, Immune Suppression

Intervention / Treatment
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* Procedure: Blood test


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (Immunocompromised Haematology Patients) Aged 18 years and over; Has one or more haematological disorder(s) with compromised immunity or currently receiving or recently treated (within previous 3 months of the screening appointment date) with immunosuppressive therapy, chemotherapy, radiotherapy or stem cell transplantation; Has had at least 2 doses of Covid-19 vaccine; Willing and able to give fully informed consent; Willing and able to comply with the study procedures; Anticipated life expectancy of over 6 months. Exclusion Criteria (Immunocompromised Haematology Patients) Has declined or does not wish to have Covid-19 vaccine; Is receiving regular IV Immunoglobulins for immunodeficiency; Is taking part in an interventional Covid-19 vaccine study; Ineligible* for Covid-19 vaccine; Non-English speaker where translation facilities are insufficient to guarantee informed consent. Ineligible for health reasons and/or as per Government prioritisation of vaccinations Inclusion Criteria (Control group - Immunocompetent Volunteers) Aged 18 years and over; Is immunocompetent; Has had at least 2 doses of Covid-19 vaccine; Anticipated life expectancy of over 6 months; Willing and able to give fully informed consent; Willing and able to comply with the study procedures. Exclusion Criteria (Control group - Immunocompetent Volunteers) Has declined or does not wish to have Covid-19 vaccine; Has comorbidity known to result in immune suppression; Has received treatment (within previous 12 months of the screening appointment) with immunosuppressive therapy, chemotherapy, radiotherapy or stem cell transplantation; Is taking part in an interventional Covid-19 vaccine study; Ineligible for Covid-19 vaccine*; Non-English speaker where translation facilities are insufficient to guarantee informed consent. Ineligible for health reasons and/or as per Government prioritisation of vaccinations

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Immunocompromised patients (study group)<br>People who are likely to have a suppressed immunity due to their haematological disorder or its treatment | Procedure: Blood test<br>* Participants will have blood tests at baseline (nearest 30 day incremental time point after 2nd dose of Covid-19 vaccine, +/- 7 days): T, B & NK cells Full Blood Count and differential Serum Immunoglobulins Antibodies against VZV, CMV, Rubella Quantiferon assay (T-Cell response) Covid antibody assay (LIAISON® SARS-CoV-2 S1/S2 IgG quantitative assay) Participants will have blood tests during follow up (after second dose of Covid-19 vaccine) with a window of +/- 7 days: Blood test 2 - performed at the next 30 day time point (Covid antibody assay) Blood test 3 - performed at the next 30 day time point (Covid antibody assay and quantiferon* if final blood test) Blood test 4 (optional) - performed at the next 30 day time point (Covid antibody assay) Blood test 5 (optional) - performed at the next 30 day time point (Covid antibody assay and quantiferon* if final blood test) Quantiferon assay will be only be performed where possible.<br>|
| Immunocompetent volunteers (control group)<br>People without suppressed immunity | Procedure: Blood test<br>* Participants will have blood tests at baseline (nearest 30 day incremental time point after 2nd dose of Covid-19 vaccine, +/- 7 days): T, B & NK cells Full Blood Count and differential Serum Immunoglobulins Antibodies against VZV, CMV, Rubella Quantiferon assay (T-Cell response) Covid antibody assay (LIAISON® SARS-CoV-2 S1/S2 IgG quantitative assay) Participants will have blood tests during follow up (after second dose of Covid-19 vaccine) with a window of +/- 7 days: Blood test 2 - performed at the next 30 day time point (Covid antibody assay) Blood test 3 - performed at the next 30 day time point (Covid antibody assay and quantiferon* if final blood test) Blood test 4 (optional) - performed at the next 30 day time point (Covid antibody assay) Blood test 5 (optional) - performed at the next 30 day time point (Covid antibody assay and quantiferon* if final blood test) Quantiferon assay will be only be performed where possible.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Anti-SARS-COV2 IgG antibodies in immunocompromised haematology patients compared to immunocompetent controls over a 4 month period | Anti-SARS-COV2 IgG antibodies | Nearest 30 day time point after 2nd dose Covid-19 vaccination (baseline) and every 30 days (3-5 follow-up time points) after 2nd dose of Covid-19 vaccination (+/- 7 days) | 
| Duration of Anti-SARS-COV2 IgG antibody response in immunocompromised haematology patients compared to immunocompetent controls over a 4 month period | Duration of Anti-SARS-COV2 IgG antibody response | Nearest 30 day time point after 2nd dose Covid-19 vaccination (baseline) | 
| Duration of Anti-SARS-COV2 IgG antibody response in immunocompromised haematology patients compared to immunocompetent controls over a 4 month period | Duration of Anti-SARS-COV2 IgG antibody response | 30 days follow-up (+/- 7 days) | 
| Duration of Anti-SARS-COV2 IgG antibody response in immunocompromised haematology patients compared to immunocompetent controls over a 4 month period | Duration of Anti-SARS-COV2 IgG antibody response | 60 days follow-up (+/- 7 days) | 
| Duration of Anti-SARS-COV2 IgG antibody response in immunocompromised haematology patients compared to immunocompetent controls over a 4 month period | Duration of Anti-SARS-COV2 IgG antibody response | 90 days follow-up (+/- 7 days) - optional | 
| Duration of Anti-SARS-COV2 IgG antibody response in immunocompromised haematology patients compared to immunocompetent controls over a 4 month period | Duration of Anti-SARS-COV2 IgG antibody response | 120 days follow-up (+/- 7 days) - optional | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation in antibody response with patient gender | Gender and anti-SARS-Cov-2 IgG antibodies | From recruitment until up to 120 days follow-up (+/- 7 days) | 
| Correlation in antibody response with patient ethnicity | Ethnicity and anti-SARS-Cov-2 IgG antibodies | From recruitment until up to 120 days follow-up (+/- 7 days) | 
| Correlation in antibody response with patient haematological disorder | Haematological disorder and anti-SARS-Cov-2 IgG antibodies | From recruitment until up to 120 days follow-up (+/- 7 days) | 
| Correlation in antibody response with patient age | Age and anti-SARS-Cov-2 IgG antibodies | From recruitment until up to 120 days follow-up (+/- 7 days) | 
| Correlation in antibody response with patient treatment | Treatment and anti-SARS-Cov-2 IgG antibodies | From recruitment until up to 120 days follow-up (+/- 7 days) | 
| Correlation in antibody response with patient Covid-19 vaccine type | Covid-19 vaccine type and anti-SARS-Cov-2 IgG antibodies | From recruitment until up to 120 days follow-up (+/- 7 days) | 
| Correlation in antibody response with patient pre-vaccine immunological parameters | Pre-vaccine immunological parameters and anti-SARS-Cov-2 IgG antibodies | From recruitment until up to 120 days follow-up (+/- 7 days) | 
| Adverse events associated with the first and second dose of a Covid-19 vaccination, reported by the study group and control group | Any participant-reported adverse events via baseline CRF | From recruitment until up to 120 days follow-up (+/- 7 days) | 
| PCR positive Covid-19 infections reported by the study group and control group | Patient reported Covid-19 PCR test via CRF, if performed on participant (routine PCR testing is not part of study) | From recruitment until up to 120 days follow-up (+/- 7 days, as reported during this time frame) | 
| T-Cell response after second dose Covid-19 vaccination in immunocompromised haematology patients compared to immunocompetent controls over a 4 month period | T-Cell cytokine response to 2nd dose Covid-19 vaccine | From recruitment and at 60 or 90 days follow-up (+/- 7 days) | 
| Duration of T-Cell response after second dose Covid-19 vaccination in immunocompromised haematology patients compared to immunocompetent controls over a 4 month period | Duration of T-Cell cytokine response to 2nd dose Covid-19 vaccine | From recruitment and at 60 or 90 days follow-up (+/- 7 days) |