Monitoring of Measles-specific Immune Status in Adult Allogeneic Hematopoietic Stem Cell Transplant Recipients

NCT05947864 | Recruiting

• 2 other identifiers: 69HCL23_03642023-A00901-44
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Transplantation, Hematopoietic Stem Cell

Outcome Measures

Primary Outcomes (1)

• 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])

  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

  At Day 1, before routine vaccination with MMR in allo-HSCT recipients

Secondary Outcomes (7)

• Kinetics of anti-measles total IgG and IgA titers (serum)

  At Day 1, Day 35, Day 70 and Day 365 in allo-HSCT recipients

• Kinetics of anti-measles neutralizing antibody titers (serum)

  At Day 1, Day 70 and Day 365 in allo-HSCT recipients

• 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

  At Day 365, after completion of MMR (re)vaccination schedule in allo-HSCT recipients

• Kinetics of anti-measles IgA titers (oral fluid)

  At Day 1 and Day 70 in allo-HSCT recipients

• 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

  At Day 1 and Day 70

Study Arms (2)

Allo-HSCT recipients

EXPERIMENTAL

Adult recipients of allogenic hematopoietic stem cell transplantation, eligible for live-attenuated vaccines, i.e. who are more than 24 months after their HSCT, without GVHD and more than 3 months after cessation of any immunosuppressant treatment

Biological: Biological samples (blood and oral fluid)

Healthy volunteers (HV)

PLACEBO COMPARATOR

Healthy adults with a history of measles (=convalescents) or vaccinated with two doses of MMR in the past (=vaccinated)

Biological: Biological samples (blood and oral fluid)

Interventions

Biological samples (blood and oral fluid) BIOLOGICAL

For 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)

Allo-HSCT recipients; Healthy volunteers (HV)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Study population:
• History of autoimmune disease or acquired immunodeficiency (other than the hematological disease),
• 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,
• 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),
• Persons deprived of liberty by judicial or administrative decision.

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (1)

Hôpital de la Croix Rousse - service des maladies infectieuses et tropicales

Lyon, France

RECRUITING

MeSH Terms

Interventions

Blood Specimen Collection; Fluid Therapy

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Drug Therapy; Therapeutics

Study Officials

• Anne CONRAD

  Hospices Civils de Lyon

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anne CONRAD

CONTACT

+33 4 72 07 11 07; anne.conrad@chu-lyon.fr

Florence ADER

CONTACT

+33 4 72 07 11 07; florence.ader@chu-lyon.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2023
• First Posted: July 17, 2023
• Study Start: August 17, 2023
• Primary Completion: July 1, 2025
• Study Completion (Estimated): July 1, 2026
• Last Updated: August 22, 2023

Record last verified: 2023-08

Locations

FR (1)