Restoration of Immunity to Vaccine Preventable Diseases After CART-T Cell Therapy
NCT ID: NCT06333275
Last Updated: 2024-03-27
Study Results
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Basic Information
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RECRUITING
80 participants
OBSERVATIONAL
2023-11-14
2026-12-31
Brief Summary
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* 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
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Detailed Description
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CAR-T therapy for B-cell malignancies involves extracting lymphocytes from a patient's 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 patient's 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 trials\[Sterner 2021, Haslauer 2021\], 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 system\[Kampouri 2022\]. 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 (hypogammaglobulinemia)\[Haslauer 2021\]. The negative effects of CAR-T cell therapies on antibody concentrations leave individuals at risk of infection for a prolonged period\[Wang 2020, Stewart 2021\]. Currently, there is limited knowledge about the extent of loss of immunity against vaccine preventable diseases after CAR-T cell therapy\[Kampouri 2022, Walti 2021\]. 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 pathogens\[Hill 2020, Wudhikarn 2022\]. 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 recommendations\[Hill 2020, Los-Arcos 2021\] , is a reasonable approach. The vaccinations that are administered during the study period are usual care interventions according to published expert-opinion based guidelines\[Hill 2020, Los-Arcos 2021, Plotkin 2010, FOPH\]. 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 (e.g. 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. 7.3.) Sampling includes minimal risk (e.g. 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.
Conditions
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Study Design
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COHORT
PROSPECTIVE
Study Groups
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CAR T-cell recipients
Patients with B-cell malignancies receiving anti-CD19 or anti-BCMA CAR T-cell therapies
Vaccines against: Diphtheria, tetanus, pertussis, polio, haemophilus influenza type b, varicella and measles
First immunization course (6±1 months post CAR-T treatment):
1. Diphtheria, tetanus, pertussis, polio, haemophilus influenza type b (as by the Swiss guidelines\[FOPH\] all of these are administered in one combined vaccine; INFANRIX DTPa-IPV+Hib Inj Susp®; GlaxoSmithKline)
2. Hepatitis B (Engerix B®, GlaxoSmithKline)
3. 13-valent Streptococcus pneumonia vaccine (Prevenar-13®; Pfizer)
4. Herpes zoster vaccine in patients with documented prior seropositivity or known varicella-infection in patient history (as by The Swiss guidelines; Shingrix®; GlaxoSmithKline)
5. Tick-borne encephalitis (as by The Swiss guidelines; FSME Immun CC®; Pfizer or Encepur N®, BavarianNordic; these vaccines can be used interchangeably)
Second immunization course (12±1 months post CAR-T treatment):
1. Mumps, measles, rubella (Priorix®, GlaxoSmithKline)
2. Varicella zoster vaccine (as by guidelines; Varilrix®, GlaxoSmithKline) If seronegative/patient history negative
Interventions
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Vaccines against: Diphtheria, tetanus, pertussis, polio, haemophilus influenza type b, varicella and measles
First immunization course (6±1 months post CAR-T treatment):
1. Diphtheria, tetanus, pertussis, polio, haemophilus influenza type b (as by the Swiss guidelines\[FOPH\] all of these are administered in one combined vaccine; INFANRIX DTPa-IPV+Hib Inj Susp®; GlaxoSmithKline)
2. Hepatitis B (Engerix B®, GlaxoSmithKline)
3. 13-valent Streptococcus pneumonia vaccine (Prevenar-13®; Pfizer)
4. Herpes zoster vaccine in patients with documented prior seropositivity or known varicella-infection in patient history (as by The Swiss guidelines; Shingrix®; GlaxoSmithKline)
5. Tick-borne encephalitis (as by The Swiss guidelines; FSME Immun CC®; Pfizer or Encepur N®, BavarianNordic; these vaccines can be used interchangeably)
Second immunization course (12±1 months post CAR-T treatment):
1. Mumps, measles, rubella (Priorix®, GlaxoSmithKline)
2. Varicella zoster vaccine (as by guidelines; Varilrix®, GlaxoSmithKline) If seronegative/patient history negative
Eligibility Criteria
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Inclusion Criteria
* Suffering from a B-cell malignancy (B-cell acute lymphoblastic leukemia (ALL), B-cell non-hodgkin lymphoma (NHL), Follicular lymphoma (FL), Mantle Cell Lymphoma (MCL), Multiple myeloma (MM))
* Planned for a CAR-T cell therapy
* Provided written informed consent
Exclusion Criteria
* \< 18 years old
* Lack of consent
18 Years
ALL
No
Sponsors
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Insel Gruppe AG, University Hospital Bern
OTHER
Responsible Party
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Principal Investigators
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Christine Thurnheer Zürcher, PD, MD
Role: PRINCIPAL_INVESTIGATOR
University Hospital Bern, Switzerland
Cédric Hirzel, PD, MD
Role: PRINCIPAL_INVESTIGATOR
University Hospital Bern, Switzerland
Locations
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University Hospital Bern
Bern, , Switzerland
Countries
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Central Contacts
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Facility Contacts
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References
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Feins S, Kong W, Williams EF, Milone MC, Fraietta JA. An introduction to chimeric antigen receptor (CAR) T-cell immunotherapy for human cancer. Am J Hematol. 2019 May;94(S1):S3-S9. doi: 10.1002/ajh.25418. Epub 2019 Feb 18.
Sterner RC, Sterner RM. CAR-T cell therapy: current limitations and potential strategies. Blood Cancer J. 2021 Apr 6;11(4):69. doi: 10.1038/s41408-021-00459-7.
Haslauer T, Greil R, Zaborsky N, Geisberger R. CAR T-Cell Therapy in Hematological Malignancies. Int J Mol Sci. 2021 Aug 20;22(16):8996. doi: 10.3390/ijms22168996.
Wang Y, Liu Y, Tan X, Pan B, Ge J, Qi K, Cheng H, Cao J, Shi M, Yan Z, Qiao J, Jing G, Wang X, Sang W, Xia R, Zhang X, Li Z, Gale RP, Zheng J, Zhu F, Xu K. Safety and efficacy of chimeric antigen receptor (CAR)-T-cell therapy in persons with advanced B-cell cancers and hepatitis B virus-infection. Leukemia. 2020 Oct;34(10):2704-2707. doi: 10.1038/s41375-020-0936-4. Epub 2020 Jun 27.
Stewart AG, Henden AS. Infectious complications of CAR T-cell therapy: a clinical update. Ther Adv Infect Dis. 2021 Aug 24;8:20499361211036773. doi: 10.1177/20499361211036773. eCollection 2021 Jan-Dec.
Kampouri E, Walti CS, Gauthier J, Hill JA. Managing hypogammaglobulinemia in patients treated with CAR-T-cell therapy: key points for clinicians. Expert Rev Hematol. 2022 Apr;15(4):305-320. doi: 10.1080/17474086.2022.2063833. Epub 2022 Apr 11.
Walti CS, Krantz EM, Maalouf J, Boonyaratanakornkit J, Keane-Candib J, Joncas-Schronce L, Stevens-Ayers T, Dasgupta S, Taylor JJ, Hirayama AV, Bar M, Gardner RA, Cowan AJ, Green DJ, Boeckh MJ, Maloney DG, Turtle CJ, Hill JA. Antibodies against vaccine-preventable infections after CAR-T cell therapy for B cell malignancies. JCI Insight. 2021 Jun 8;6(11):e146743. doi: 10.1172/jci.insight.146743.
Hill JA, Seo SK. How I prevent infections in patients receiving CD19-targeted chimeric antigen receptor T cells for B-cell malignancies. Blood. 2020 Aug 20;136(8):925-935. doi: 10.1182/blood.2019004000.
Wudhikarn K, Perales MA. Infectious complications, immune reconstitution, and infection prophylaxis after CD19 chimeric antigen receptor T-cell therapy. Bone Marrow Transplant. 2022 Oct;57(10):1477-1488. doi: 10.1038/s41409-022-01756-w. Epub 2022 Jul 15.
Los-Arcos I, Iacoboni G, Aguilar-Guisado M, Alsina-Manrique L, Diaz de Heredia C, Fortuny-Guasch C, Garcia-Cadenas I, Garcia-Vidal C, Gonzalez-Vicent M, Hernani R, Kwon M, Machado M, Martinez-Gomez X, Maldonado VO, Pla CP, Pinana JL, Pomar V, Reguera-Ortega JL, Salavert M, Soler-Palacin P, Vazquez-Lopez L, Barba P, Ruiz-Camps I. Recommendations for screening, monitoring, prevention, and prophylaxis of infections in adult and pediatric patients receiving CAR T-cell therapy: a position paper. Infection. 2021 Apr;49(2):215-231. doi: 10.1007/s15010-020-01521-5. Epub 2020 Sep 26.
Plotkin SA. Correlates of protection induced by vaccination. Clin Vaccine Immunol. 2010 Jul;17(7):1055-65. doi: 10.1128/CVI.00131-10. Epub 2010 May 12.
Related Links
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Swiss Federal Office of Public Health (FOPH)
Other Identifiers
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BASEC-Nr: 2023-01141
Identifier Type: OTHER
Identifier Source: secondary_id
DLF-Nr: 5564
Identifier Type: -
Identifier Source: org_study_id
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