Prospective Study on the Vaccine Response to Meningococcal B Vaccine After Allogeneic Stem Cell Transplantation

Overview

Allogeneic hematopoietic stem cell transplant (HSCT) recipients are at risk of various bacterial infections, especially due to a progressive decrease of specific antibodies. Around 90% of HSCT recipients have unprotective titers of specific antibodies to serogroups A and C meningogocci (Parkkali 2001; Mahler 2012). Some small studies suggest that the response to meningococcal A and C vaccines is close to 100% after 3 doses given 18 months after transplant. Although the response to 2 doses of 4CMenB is over 75% in other immunocompromised patients (Feavers, 2017), studies with 4CMenB are lacking after HSCT. Nevertheless, as serogroup B caused 74% of IMD in Europe between 2004-2014 (Whittaker, 2017), the meningococcal B vaccination is recommended by the more recent guidelines from 6 months after transplant. There are, however, no data on the safety and efficacy of this vaccine after hematopoietic stem cell allograft (HSCT). The objective of this study is to assess the response to 2 doses of a multicomponent meningococcal B vaccine (4CMenB) given at 2 months interval in adult allogeneic HSCT recipients transplanted at least 6 months ago. The response will be assessed 1 month and 10 months after the second dose of vaccine by measuring bactericidal antibodies against NadA, fHbp, NHBA and PorAP1 vaccinal antigens according to methods previously reported (Caron Lancet Infect Dis 2011). The response rate will be correlated to pre- and post-transplant factors. The hypothesis of this study is that 80% of the patients should have protective titers one month after the 2nd dose.

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Prevention
    • Masking: None (Open Label)
  • Study Primary Completion Date: March 13, 2020

Detailed Description

Monocentric study. Forty patients are expected. Primary objective: Response rate one month after 2 doses of vaccine Secondary objectives: safety, rate of protection before vaccination, comparison of the antibody titers at one month vs. at 10 months after the vaccine program. Relationship between pre and post-transplant factors.

Interventions

  • Biological: B vaccination
    • One intramuscular injection of Bexsero (multicomponent B vaccine) from 6 months after transplant. A second similar dose will be given 2 months later.

Arms, Groups and Cohorts

  • Experimental: B vaccination
    • One intramuscular injection of Bexsero (multicomponent B vaccine) from 6 months after transplant. A second similar dose will be given 2 months later.

Clinical Trial Outcome Measures

Primary Measures

  • % of patients with Bactericidal titers > 4 to at least one component of the Bexsero vaccine, 1 month after the 2nd dose.
    • Time Frame: 1 month
    • Vaccine response rate at one month after the 2nd dose.

Secondary Measures

  • % of patients with Bactericidal titers > 4 to at least one component of the Bexsero vaccine, 12 months after the 1st dose.
    • Time Frame: 12 month
    • Vaccine response rate at 12 month after the 1st dose.
  • Number of adverse events of vaccination by Bexsero after Allograft of CSH.
    • Time Frame: 12 month
    • Number of adverse events (non serious and serious) reported during the study

Participating in This Clinical Trial

Inclusion Criteria

  • Allogeneic HSCT at least 6 months before – Age ≥ 18 years – Platelet count > 50 G/L Exclusion Criteria:

  • Rituximab administration in the previous 6 months – Relapse of the underlying disease

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Assistance Publique – Hôpitaux de Paris
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Christine Robin, MD, Principal Investigator, Assistance Publique des Hopitaux de Paris

References

Caron F, du Chatelet IP, Leroy JP, Ruckly C, Blanchard M, Bohic N, Massy N, Morer I, Floret D, Delbos V, Hong E, Revillion M, Berthelot G, Lemee L, Deghmane AE, Benichou J, Levy-Bruhl D, Taha MK. From tailor-made to ready-to-wear meningococcal B vaccines: longitudinal study of a clonal meningococcal B outbreak. Lancet Infect Dis. 2011 Jun;11(6):455-63. doi: 10.1016/S1473-3099(11)70027-5. Epub 2011 Apr 12. Erratum In: Lancet Infect Dis. 2011 Jul;11(7):495.

Mahler MB, Taur Y, Jean R, Kernan NA, Prockop SE, Small TN. Safety and immunogenicity of the tetravalent protein-conjugated meningococcal vaccine (MCV4) in recipients of related and unrelated allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2012 Jan;18(1):145-9. doi: 10.1016/j.bbmt.2011.07.027. Epub 2011 Aug 4.

Parkkali T, Kayhty H, Lehtonen H, Ruutu T, Volin L, Eskola J, Ruutu P. Tetravalent meningococcal polysaccharide vaccine is immunogenic in adult allogeneic BMT recipients. Bone Marrow Transplant. 2001 Jan;27(1):79-84. doi: 10.1038/sj.bmt.1702742.

Rubin LG, Levin MJ, Ljungman P, Davies EG, Avery R, Tomblyn M, Bousvaros A, Dhanireddy S, Sung L, Keyserling H, Kang I; Infectious Diseases Society of America. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis. 2014 Feb;58(3):309-18. doi: 10.1093/cid/cit816. Erratum In: Clin Infect Dis. 2014 Jul 1;59(1):144.

Whittaker R, Dias JG, Ramliden M, Kodmon C, Economopoulou A, Beer N, Pastore Celentano L; ECDC network members for invasive meningococcal disease. The epidemiology of invasive meningococcal disease in EU/EEA countries, 2004-2014. Vaccine. 2017 Apr 11;35(16):2034-2041. doi: 10.1016/j.vaccine.2017.03.007. Epub 2017 Mar 14.

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.