Immunogenicity of COVID-19 Vaccinations in Autologous HSCT Recipients

Study Overview
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Brief Summary
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This multicenter, prospective, non-interventional cohort study aims to evaluate data on humoral and cellular immune response generated within the COVID-19 vaccination standard in patients with B-cell non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HL) who underwent autologous hematopoietic stem cell transplantation (HSCT).

Detailed Description
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According to the local COVID-19 vaccination standard, patients who underwent autologous HSCT will receive between 3 to 8 anti-SARS-CoV-2 mRNA vaccination in 28-day intervals. The definitive number of vaccinations patients will receive depend on the individual neutralizing antibody response. Anti-SARS-CoV-2 immune parameters in successfully vaccinated patients will be followed-up for a total of 24-weeks. This study aims to analyze the immune response data generated within the procedures of the standard-of-care COVID-19 vaccination. Additional blood will be drawn from the patients at each visit defined within the vaccination standard by using the same vein puncture as used for blood drawings of routine blood samples. Study related blood samples will be used for evaluation of T and B cell response to COVID-19 vaccinations.

Official Title
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Immunogenicity of Repeated COVID-19 Vaccination in Patients Post Autologous Stem Cell Transplantation

Conditions
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COVID-19, Non Hodgkin Lymphoma, Hodgkin Lymphoma, Adult

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient 42 days (±3) post autologous HSCT for B-cell non-Hodgkin lymphoma or Hodgkin lymphoma. Patient is 30 years of age or older at enrollment. Patients are eligible for study inclusion with or without confirmed SARS-CoV-2 infection prior to autologous HSCT. Patient is treated at an institution that practices the standard-of-care COVID-19 vaccination. Patient has received 3 or more vaccinations with an anti-SARS-CoV-2 mRNA vaccine prior to autologous HSCT. Patient planned to be vaccinated against COVID-19 according to the hospital standard. Written informed consent from patient has been obtained prior to any study related procedures. Exclusion Criteria: Patient with confirmed SARS-CoV-2 infection between d0 and d42 after autologous HSCT. Patient has a positive SARS-CoV-2 antigen test at visit d42. Patient has received less than 3 vaccinations with an anti-SARS-CoV-2 mRNA vaccine prior to autologous HSCT. Use of any investigational or non-registered product (vaccine or drug) within 28 days preceding enrollment. Planned use during the study of any investigational or non-registered product (vaccine or drug).

Ages Eligible for Study
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Minimum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Omicron BA.1-specific neutralizing antibody titer | Time to Omicron BA.1-specific neutralizing antibody 50% inhibitory dilution (ID50) titers ≥20/ml in serum after repeated mRNA vaccinations. | At the end of each vaccination cycle (each cycle is 28 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Omicron BA.2-specific neutralizing titer | Time to Omicron BA.2-specific neutralizing ID50 titers ≥20/ml in serum after repeated mRNA vaccinations | At the end of each vaccination cycle (each cycle is 28 days) | 
| Time to anti-Spike-1/2 IgG increase | Time to anti-Spike-1/2 IgG increase >33.8 BAU/ml in serum after repeated mRNA vaccinations in patients post autologous HSCT | At the end of each vaccination cycle (each cycle is 28 days) | 
| Time to anti-RBD IgG increase | Time to anti-RBD IgG increase >7.1 BAU/ml in serum after repeated mRNA vaccinations in patients post autologous HSCT | At the end of each vaccination cycle (each cycle is 28 days) | 
| Time to anti-Spike-2 IgG increase | Time to anti-Spike-2 IgG increase >2x optical density in serum of the negative control | At the end of each vaccination cycle (each cycle is 28 days) | 
| Waning of BA.1 neutralizing antibodies | Time to decrease of Omicron BA.1-specific neutralizing antibody ID50 titers <20/ml after last mRNA vaccine in successfully vaccinated patients | Every 28 days following last COVID-19 vaccination for a total duration of 24 weeks | 
| Waning of BA.2 neutralizing antibodies | Time to decrease of Omicron BA.2-specific neutralizing antibody ID50 titers <20/ml after last mRNA vaccine in successfully vaccinated patients | Every 28 days following last COVID-19 vaccination for a total duration of 24 weeks | 
| Waning of anti-Spike-1/2 IgG | Time to anti-Spike-1/2 IgG decrease ≤33.8 BAU/ml after last mRNA vaccine in successfully vaccinated patients. | Every 28 days following last COVID-19 vaccination for a total duration of 24 weeks | 
| Waning of anti-RBD IgG | Time to anti-RBD IgG decrease ≤7.1 BAU/ml after last mRNA vaccine in successfully vaccinated patients. | Every 28 days following last COVID-19 vaccination for a total duration of 24 weeks | 
| Waning of anti-Spike-2 IgG | Time to anti-Spike-2 IgG decrease ≤2x optical density of the negative control | Every 28 days following last COVID-19 vaccination for a total duration of 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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B-cell non-Hodgkin lymphoma, COVID-19, Hodgkin lymphoma, mRNA vaccination, post autologous stem cell transplantation