Impact of the Immune System on Response to Anti-Coronavirus Disease 19 (COVID-19) Vaccine in Allogeneic Stem Cell Recipients (Covid Vaccin Allo)

Study Overview
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Brief Summary
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The present study is a prospective phase IV study. All participants will receive the anti-Coronavirus Disease 2019 (COVID-19) Vaccine (messenger Ribonucleic acid-based vaccine, BNT162b2 or Comirnaty®, commercialized by Pfizer-BioNTech) being authorized in the European Union since December 2020. The vaccine is administered intramuscularly after dilution as a series of two doses at least 21 days apart.

Detailed Description
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The central question is whether allo-hematopoietic cell transplantation (allo-HCT) recipients can develop protective immunity against COVID-19 upon vaccination. This question needs to be answered urgently and would help the hematologist to provide recommendation / best treatment for these patients. In this pilot project Cov-Allo, this important question will be addressed in a cohort in which allo-HCT recipients will be vaccinated with the mRNA available COVID-19 vaccine according to the Belgian vaccination program. The primary objective is to assess immune response after administration of COVID-19 mRNA Vaccine BNT162b2 (Comirnaty®; Pfizer-BioNTech) in a population of 50 patients allo-HCT recipients. This number is based on the availabilities of vaccines and eligible patients. Moreover, as the study is observational and exploratory, no sample size calculation could be provided for this study.

Official Title
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Impact of the Immune System on Response to COVID-19 Vaccine in Allogeneic Stem Cell Recipients (Covid Vaccin Allo)

Conditions
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Coronavirus Disease 2019 (Covid19), Hematopoietic Neoplasms

Intervention / Treatment
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* Drug: anti-COVID19 mRNA-based vaccine (BNT162b2, Comirnaty®, commercialized by Pfizer)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: prior allogeneic hematopoietic stem cell transplantation 3 months to 5 years earlier (any donor type) age > or = 18 years at inclusion. written informed consent Exclusion Criteria: HIV seropositivity Pregnancy Active malignant disease at inclusion Current grade III-IV acute Graft Versus Host Disease (GVHD) In vitro T-cell depletion of the graft if vaccination within the 6 months after transplantation. Rituximab administration in the 6 months prior to study inclusion Prior documented COVID-19 infection

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 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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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Injection of anti-COVID19 mRNA-based vaccine (BNT162b2, Comirnaty®, commercialized by Pfizer)<br>Injection of two doses (at Day 1 and Day 21) of the anti-COVID19 mRNA-based vaccine (BNT162b2, Comirnaty®, commercialized by Pfizer) | Drug: anti-COVID19 mRNA-based vaccine (BNT162b2, Comirnaty®, commercialized by Pfizer)<br>* Participants will receive the COVID-19 mRNA Vaccine BNT162b2 (Comirnaty®). The vaccine is administered intramuscularly after dilution as a series of two doses at least 21 days apart.<br>* Other names: Pfizer;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantification of anti-SARS-CoV-2 receptor binding domain specific IgG | The primary endpoint is the quantification of different anti-SARS-CoV-2 specific IgG antibodies after vaccination (at Day 49) in allo-HCT recipients. | Day 49 after first injection (D0) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evolution of anti-SARS-CoV-2 receptor binding domain specific IgG | To study the evolution anti-RBD IgG titers from day +49 (day 28 after the second dose) to 6 months after the second dose. | 6 months after day 21 | 
| Titration of neutralizing antibodies | To analyze the titer of neutralizing antibodies at Day 49 as well as at 6 months after the second dose (at Day 21). | Day 49 and 6 months after Day 21 | 
| Clinical factors predicting response to vaccine (defined as detectable specific anti-SARS-CoV-2 RBD specific IgG). | This point aims at trying to find correlations between patient immunity at vaccination and response to vaccination and also to correlate pre-vaccination clinical factors (such as delay from transplantation to vaccination in days, presence or not of moderate/severe chronic GVHD (assessed using the NIH criteria), administration of rituximab in the year before vaccination) response to the vaccine defined as detectable specific anti-SARS-CoV-2 RBD specific IgG. | 49 days after the first dose | 
| Efficacy of the immune response to the vaccine to prevent COVID-19 | Incidence of SARS-CoV-2 infection occurring after vaccination | 12 months after first dose (Day 0) | 
| Assessment of T cell and B cell response to the vaccine | Measuring SARS-Cov2 specific T cells (by intracellular cytokine staining) and B cells (by Elispot). | Day 7 and Day 49 |