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

Hematopoietic Stem Cell Transplant Clinical Trial

— MENINGREF  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03509051
• Other study ID #: K180302J
• Status: Completed
• Phase: N/A
• Start date: June 1, 2019
• Est. completion date: March 13, 2020

Study information

• Verified date: September 2020
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: March 13, 2020
• Est. primary completion date: March 13, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hematopoietic Stem Cell Transplant
• Meningococcal Vaccine

Intervention

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.

Locations

Country	Name	City	State
France	Henri-Mondor Hospital	Créteil	Val De Marne

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

References & Publications (5)

Caron F, du Châtelet IP, Leroy JP, Ruckly C, Blanchard M, Bohic N, Massy N, Morer I, Floret D, Delbos V, Hong E, Révillion M, Berthelot G, Lemée L, Deghmane AE, Bénichou J, Lévy-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. — View Citation

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. — View Citation

Parkkali T, Käyhty 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. — View Citation

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. — View Citation

Whittaker R, Dias JG, Ramliden M, Ködmön 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	% of patients with Bactericidal titers > 4 to at least one component of the Bexsero vaccine, 1 month after the 2nd dose.	Vaccine response rate at one month after the 2nd dose.	1 month
Secondary	% of patients with Bactericidal titers > 4 to at least one component of the Bexsero vaccine, 12 months after the 1st dose.	Vaccine response rate at 12 month after the 1st dose.	12 month
Secondary	Number of adverse events of vaccination by Bexsero after Allograft of CSH.	Number of adverse events (non serious and serious) reported during the study	12 month