Ignite Creation Date:
2024-05-06 @ 8:18 PM
Last Modification Date:
2024-10-26 @ 3:25 PM
Study NCT ID:
NCT06333275
Status:
RECRUITING
Last Update Posted:
2024-03-27
First Post:
2024-03-20
Brief Title:
Restoration of Immunity to Vaccine Preventable Diseases After CART-T Cell Therapy
Sponsor:
Insel Gruppe AG University Hospital Bern
Organization:
Insel Gruppe AG University Hospital Bern
Study Overview
Official Title:
Restoration of Immunity to Vaccine Preventable Diseases After CART-T Cell Therapy
Status:
RECRUITING
Status Verified Date:
2024-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
IMCAR
Brief Summary:
The goal of this observational study is to learn about vaccine immunity in patients with B-cell malignancies treated by chimeric antigen receptor T-cell therapies CAR-T The main questions it aims to answer are
Do CAR-T cell therapy recipients lose vaccine protection against common vaccine-preventable pathogens
Are current re-vaccination recommendations sufficient in restoring vaccine-protection
Is this restored vaccine-protection after CAR-T cell therapy lost faster than usual
Do clinical or immunological factors predict vaccine response after CAR-T cell therapy
Do CAR-T cell therapy recipients lose vaccine protection against common vaccine-preventable pathogens
Are current re-vaccination recommendations sufficient in restoring vaccine-protection
Is this restored vaccine-protection after CAR-T cell therapy lost faster than usual
Do clinical or immunological factors predict vaccine response after CAR-T cell therapy
Detailed Description:
B-cell malignancies are a diverse group of cancers that arise from abnormal growth and proliferation of B-cells a type of cells that plays a crucial role in the immune system The function of B-cells comprises the production of antibodies immunoglobulins Antibodies bind to specific molecules antigens on the surface of pathogens eg viruses bacteria marking them for destruction by other components of the immune system B-cell malignancies can arise from various stages of B-cell development and can manifest as a range of clinical presentations from lymphomas with diverse clinical courses to aggressive leukemias Treatment options for B-cell malignancies vary depending on the specific type of cancer and the stage of disease Recently a broad array of newer immunotherapies became availableFeins 2019 Specifically the introduction of anti-CD19 and anti- BCMA B cell maturation antigen targeted chimeric antigen receptor T- cell therapy CAR-T represents a major treatment breakthrough in treatment of many B-cell malignanciesSterner 2021 Haslauer 2021
CAR-T therapy for B-cell malignancies involves extracting lymphocytes from a patients blood and modifying them to produce chimeric antigen receptors CARs that can recognize and bind to proteins CD19 or BCMA expressed on cancer cells The modified cells are then infused into the patients bloodstream where they seek out and bind to cancer cells expressing the target proteins Once attached the CAR-T cells are activated and initiate the destruction of the bound cancer cells While CAR-T cell therapy has shown remarkable success in clinical trialsSterner 2021 Haslauer 2021 it is a new and complex treatment with potential side effects such as cytokine release syndrome neurotoxicity and a significant impact on the host immune systemKampouri 2022 The tumor antigens targeted by CAR-T cells are also expressed on healthy B-cells CD-19 and plasma-cells BCMA Therefore CAR-T therapy leads to a decline in healthy B-cell populations with a subsequent decrease in antibody production hypogammaglobulinemiaHaslauer 2021 The negative effects of CAR-T cell therapies on antibody concentrations leave individuals at risk of infection for a prolonged periodWang 2020 Stewart 2021 Currently there is limited knowledge about the extent of loss of immunity against vaccine preventable diseases after CAR-T cell therapyKampouri 2022 Walti 2021 High-quality evidence on how to prevent infections in CAR-T recipients and particularly on the necessity of re-vaccination against common vaccine-preventable pathogens is lacking Expert opinion statements recommend re-vaccinating these patients 6-12 months after CAR-T therapy against the most common pathogensHill 2020 Wudhikarn 2022 Based on available recommendations and the vaccine-guidelines provided by the Swiss Federal Office of Public Health FOPH revaccination is started 6 months after CAR-T Therapy for inactivated vaccines and 12 months after CAR-T Therapy for life-attenuated vaccines
With the present cohort study the investigators aim to explore to which extent patients lose their humoral immunity to vaccine preventable pathogens after CAR-T cell therapies Additionally the investigators assess vaccine responses to routinely administered vaccinations in this population to examine whether re-vaccination after 6 months as suggested in expert-opinion based recommendationsHill 2020 Los-Arcos 2021 is a reasonable approach The vaccinations that are administered during the study period are usual care interventions according to published expert-opinion based guidelinesHill 2020 Los-Arcos 2021 Plotkin 2010 FOPH These vaccines are presently administered to all CAR-T recipients at the University Hospital Bern and will be also administered to all CAR-T patients during the study period irrespective of study participation
The results of this cohort study will reveal if present expert-opinion based vaccination recommendations for CAR-T patients are reasonable or if there will be need for adapting the recommendations eg if it turns out that CAR-T patients do not lose protective immunity to vaccine preventable pathogens or if the study reveals that immunization according to present vaccine schedules do not elicit protective antibody levels Furthermore this project could increase fundamental understanding of immunological responses to common vaccines in the immunosuppressed population
The present project falls into the risk category A according to art 7 HRO It is a cohort study no study intervention with blood sampling low risk sampling according to HRO art 73 Sampling includes minimal risk eg hematoma after blood draw uncomfortable feeling during procedure for patients Within this project the investigators will exclusively use methods that are readily available in clinical practice flow-cytometric analysis of lymphocyte populations serology Therefore the gained knowledge will be immediately applicable in clinical practice and the results of this sub-project will help improving present vaccine strategies for CAR-T patients Vaccination schedules are according to official recommendations by the Swiss Federal Office of Public Health and according to expert-opinion based guidelines and do not differ from patients not included in the study
CAR-T therapy for B-cell malignancies involves extracting lymphocytes from a patients blood and modifying them to produce chimeric antigen receptors CARs that can recognize and bind to proteins CD19 or BCMA expressed on cancer cells The modified cells are then infused into the patients bloodstream where they seek out and bind to cancer cells expressing the target proteins Once attached the CAR-T cells are activated and initiate the destruction of the bound cancer cells While CAR-T cell therapy has shown remarkable success in clinical trialsSterner 2021 Haslauer 2021 it is a new and complex treatment with potential side effects such as cytokine release syndrome neurotoxicity and a significant impact on the host immune systemKampouri 2022 The tumor antigens targeted by CAR-T cells are also expressed on healthy B-cells CD-19 and plasma-cells BCMA Therefore CAR-T therapy leads to a decline in healthy B-cell populations with a subsequent decrease in antibody production hypogammaglobulinemiaHaslauer 2021 The negative effects of CAR-T cell therapies on antibody concentrations leave individuals at risk of infection for a prolonged periodWang 2020 Stewart 2021 Currently there is limited knowledge about the extent of loss of immunity against vaccine preventable diseases after CAR-T cell therapyKampouri 2022 Walti 2021 High-quality evidence on how to prevent infections in CAR-T recipients and particularly on the necessity of re-vaccination against common vaccine-preventable pathogens is lacking Expert opinion statements recommend re-vaccinating these patients 6-12 months after CAR-T therapy against the most common pathogensHill 2020 Wudhikarn 2022 Based on available recommendations and the vaccine-guidelines provided by the Swiss Federal Office of Public Health FOPH revaccination is started 6 months after CAR-T Therapy for inactivated vaccines and 12 months after CAR-T Therapy for life-attenuated vaccines
With the present cohort study the investigators aim to explore to which extent patients lose their humoral immunity to vaccine preventable pathogens after CAR-T cell therapies Additionally the investigators assess vaccine responses to routinely administered vaccinations in this population to examine whether re-vaccination after 6 months as suggested in expert-opinion based recommendationsHill 2020 Los-Arcos 2021 is a reasonable approach The vaccinations that are administered during the study period are usual care interventions according to published expert-opinion based guidelinesHill 2020 Los-Arcos 2021 Plotkin 2010 FOPH These vaccines are presently administered to all CAR-T recipients at the University Hospital Bern and will be also administered to all CAR-T patients during the study period irrespective of study participation
The results of this cohort study will reveal if present expert-opinion based vaccination recommendations for CAR-T patients are reasonable or if there will be need for adapting the recommendations eg if it turns out that CAR-T patients do not lose protective immunity to vaccine preventable pathogens or if the study reveals that immunization according to present vaccine schedules do not elicit protective antibody levels Furthermore this project could increase fundamental understanding of immunological responses to common vaccines in the immunosuppressed population
The present project falls into the risk category A according to art 7 HRO It is a cohort study no study intervention with blood sampling low risk sampling according to HRO art 73 Sampling includes minimal risk eg hematoma after blood draw uncomfortable feeling during procedure for patients Within this project the investigators will exclusively use methods that are readily available in clinical practice flow-cytometric analysis of lymphocyte populations serology Therefore the gained knowledge will be immediately applicable in clinical practice and the results of this sub-project will help improving present vaccine strategies for CAR-T patients Vaccination schedules are according to official recommendations by the Swiss Federal Office of Public Health and according to expert-opinion based guidelines and do not differ from patients not included in the study
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| BASEC-Nr 2023-01141 | OTHER | BASEC Business Administration System for Ethics Committees - Switzerland | None |