Hôpital de la Croix Rousse - service des maladies infectieuses et tropicales
Lyon, France
Location status: Recruiting
Recruiting
NCT Number: NCT05947864
Monitoring of Measles-specific Immune Status in Adult Allogeneic Hematopoietic Stem Cell Transplant Recipients
Measles, a highly contagious disease, is potentially serious in adult allogenic hematopoietic stem cell transplant (allo-HSCT) recipients. Because of the loss of immunity to vaccine preventable diseases after allo-HSCT, French Health Authorities (Haut Conseil de Santé Publique, HCSP) recommend (re)vaccination of all allo-HSCT recipients against measles-mumps-rubella (MMR) from 24 months post-transplant onwards, in the absence of graft-versus-host disease (GVHD) and at least 3 months after cessation of all immunosuppressive treatments, irrespective of measles serostatus. Nevertheless, some French experts argue that systematic assessment of measles antibody titre is justified after allo-HSCT, prior to revaccination, in order to avoid "unnecessary" revaccination of allo-HSCT recipients who are still seropositive. At the international level, recommendations also vary: the ECIL group and IDSA advocate revaccination of measles seronegative patients only, while some American Hematology experts recommend not to base the decision of revaccination on the serological status, given the inevitable loss of antibodies and specific long-term immune memory in the absence of revaccination.
Several obstacles to the application of the recommendations can therefore be identified: (i) the risk of vaccine-transmitted disease due to the live-attenuated nature of MMR, (ii) the lack of robust data on the immunogenicity and tolerability of the MMR vaccine in this particular population, and (iii) conflicting recommendations to guide the decision of revaccination.
This study aims at answering the question of whether some allo-HSCT recipients may retain a measles-specific cellular immune memory at distance from their allo-HSCT.
Recruiting
Interested in participating?
Request InfoKey information
Conditions
Age range
18 year–75 year
Sex eligibility
All sexes
Study type
Interventional
Phase
Not applicable
Primary location
Who can participate
Healthy volunteers accepted: Yes
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
Study population:
- Aged ≥ 18 years and ≤ 75 years,
- Have received an allo-HSCT ≥ 24 months ago,
- In complete remission of initial hematologic disease and with successful engraftment (recipient chimerism <0.3% on whole blood),
- Without extensive chronic GVHD,
- Having given their written consent,
- Affiliated to a social security plan,
- Able to attend all scheduled visits and to comply with all study procedures.
Healthy volunteers:
- Aged ≥ 18 years and ≤ 75 years,
- Having a history of measles (=convalescent) or have been vaccinated in the past with two doses of MMR (=vaccinated),
- Having given their written consent,
- Affiliated to a social security plan.
Exclusion criteria
Study population:
- History of autoimmune disease or acquired immunodeficiency (other than the hematological disease),
- Patients undergoing pharmacological immunosuppression or biotherapy or extracorporeal photopheresis at the time of inclusion, or whose immunosuppressive treatment (corticosteroids and anti-rejection agents) has been stopped less than 3 months ago, or whose biotherapy (anti-cytokines, anti-JAK, anti-CD20 etc.) has been stopped less than 3 months ago (12 months for anti-CD20 including rituximab), or whose extracorporeal photopheresis has been stopped less than 3 months ago,
- Patients having received ≥ 1 infusion of IVIG in the 8 months prior to inclusion,
- Patients whose last HSCT was an autograft,
- Patients with known chronic active infection with human immunodeficiency virus (HIV) and/or hepatitis B or C virus(es),
- Patients deprived of liberty by judicial or administrative decision,
- Patients under legal protection or unable to consent to the study,
- Patients participating in another interventional research study with an exclusion period still in progress at pre-inclusion,
- Pregnant, parturient or breast-feeding women.
Healthy volunteers:
- History of autoimmune disease or acquired immunodeficiency,
- History of pharmacological immunosuppression or biotherapy discontinued less than 3 months ago (12 months for anti-CD20 including rituximab),
- History of IVIG infusion in the 8 months prior to inclusion,
- Persons deprived of liberty by judicial or administrative decision.
Treatment and study plan
Biological samples (blood and oral fluid)
BiologicalFor the study population (allo-HSCT recipients): 4 visits with biological sampling (blood and oral fluid) at each visit:
- Visit V1 (inclusion visit = D1): immediately before the first dose of MMR (dose-1),
- Visit V2 (D1 + 35 (+/-7) days): immediately before the second dose of MMR (dose-2)
- Visit V3 (D1 + 70 (+/-14) days)
- Visit V4 (D1 + 365 (+/-90) days) For healthy volunteers: a single visit (V1) with biological sampling (blood and oral fluid)
Primary outcomes
-
Combined quantification of measles-specific markers of T-cell-mediated immunity (interferon-gamma [IFNγ]-secreting cells; copies of ifnγ mRNA transcripts; amount of IFNγ) and B-cell-mediated immunity (antibody-secreting cells [ASC])
Time frame: At Day 1, before routine vaccination with MMR in allo-HSCT recipients
To explore the measles-specific T- and B-cell-mediated systemic immune memory pre-existing to MMR (re)vaccination in allo-HSCT recipients eligible for MMR revaccination according to current French recommendations (i.e., regardless of measles serostatus), T- and B-ELISpot techniques on PBMC, qPCR and cytokine measurement on whole blood, will be performed after ex vivo antigen stimulation
Secondary outcomes
-
Kinetics of anti-measles total IgG and IgA titers (serum)
Time frame: At Day 1, Day 35, Day 70 and Day 365 in allo-HSCT recipients
To characterize the total measles-specific systemic humoral immune response before and after MMR (re)vaccination, anti-measles antibodies will be measured in serum by ELISA
-
Kinetics of anti-measles neutralizing antibody titers (serum)
Time frame: At Day 1, Day 70 and Day 365 in allo-HSCT recipients
To characterize the neutralizing measles-specific systemic humoral immune response before and after MMR (re)vaccination, neutralizing serum antibodies titers will be determined through seroneutralization techniques
-
Combined quantification of measles-specific markers of T-cell-mediated immunity (IFNγ-secreting cells; copies of ifnγ mRNA transcripts; amount of IFNγ) and B-cell-mediated immunity (ASC) after two doses of MMR
Time frame: At Day 365, after completion of MMR (re)vaccination schedule in allo-HSCT recipients
To explore the measles-specific T- and B-cell-mediated systemic immune response after completing MMR (re)vaccination, T- and B-ELISpot techniques on PBMC, qPCR and cytokine measurement on whole blood, will be performed after ex vivo antigen stimulation
-
Kinetics of anti-measles IgA titers (oral fluid)
Time frame: At Day 1 and Day 70 in allo-HSCT recipients
To characterize the measles-specific mucosal humoral immune response before and after MMR (re)vaccination, anti-measles IgA will be measured in oral fluid by ELISA
-
Difference in immunity markers (total IgG and IgA, neutralizing antibody titers [serum]; IgA titers [oral fluid]; IFNγ-secreting cells; copies of ifnγ mRNA transcripts; amount of IFNγ; ASC) between HV and allo-HSCT recipients
Time frame: At Day 1 and Day 70
To compare the measles-specific systemic and mucosal immune response between convalescent/vaccinated HV and allo-HSCT recipients, markers of B-cell and T-cell-mediated immunity will be evaluated in convalescent/vaccinated HV at a single timepoint and compared to immunity markers evaluated in allo-HSCT recipients before and after MMR (re)vaccination
-
Analysis of measles-specific immunity markers (total IgG and IgA, neutralizing antibody titers [serum]; IgA titers [oral fluid]; IFNγ-secreting cells; copies of ifnγ mRNA transcripts; amount of IFNγ; ASC) according to patient characteristics
Time frame: At Day 1, Day 35, Day 70 and Day 365 in allo-HSCT recipients
To determine the impact of demographic, hematological, transplant-related characteristics, post-transplant complications and measles serostatus on measles-specific B-cell and T-cell immunity markers, before and after MMR (re)vaccination, bivariate and multivariate analysis will be carried out
-
Local and systemic adverse events after the first and the second MMR dose
Time frame: At Day 35 and Day 70, in allo-HSCT recipients
To describe the tolerance of the two MMR schedule in allo-HSCT recipients, solicited adverse events will be recorded up to day+14 and unsolicited adverse events will be recorded up to day+28 after each MMR dose through self-monitoring
Study contacts
Contact information is provided by the study sponsor or research team.
Anne CONRAD
CONTACT
Florence ADER
CONTACT
Sponsors and collaborators
Lead sponsor
Hospices Civils de Lyon
Other
Registry information
Official study title
Monitoring of Measles-specific Immune Status in Adult Allogeneic Hematopoietic Stem Cell Transplant Recipients: a Prospective Cohort Study
Acronym: MaRROwVacc
Important dates
- Study start
- 2023
- Primary completion
- 2025
- Study completion
- 2026
- First posted
- Jul 17, 2023
- Registry last updated
- Aug 22, 2023
OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.
View the official ClinicalTrials.gov record (opens in a new tab)This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.
Related clinical trials
Published trials that share one or more normalized conditions with this study.
Completed
Study for the Evaluation of a GVHD Negative Outcome Score (GNOS) in Matched Unrelated or Haploidentical Hematopoietic Stem Cell Transplant
NCT02414113
Hematopoietic Stem Cell Transplantation, Stem Cell Transplantation, Hematopoietic
St Louis, Missouri, United States
View Trial Details