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

NCT ID: NCT05947864

Last Updated: 2023-08-22

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-08-17
• Study Completion Date: 2026-07-31

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Allo-HSCT recipients

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

Group Type: EXPERIMENTAL

Biological samples (blood and oral fluid)

Intervention Type: 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)

Healthy volunteers (HV)

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

Group Type: PLACEBO_COMPARATOR

Biological samples (blood and oral fluid)

Intervention Type: 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)

Interventions

Biological samples (blood and oral fluid)

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)

Intervention Type: BIOLOGICAL

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Hospices Civils de Lyon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anne CONRAD

Role: PRINCIPAL_INVESTIGATOR

Hospices Civils de Lyon

Locations

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

Lyon, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Anne CONRAD

Role: CONTACT

anne.conrad@chu-lyon.fr

+33 4 72 07 11 07

Florence ADER

Role: CONTACT

florence.ader@chu-lyon.fr

+33 4 72 07 11 07

Facility Contacts

Anne CONRAD, Dr

Role: primary

anne.conrad@chu-lyon.fr

+33 4 72 07 11 07

Other Identifiers

2023-A00901-44

Identifier Type: OTHER

Identifier Source: secondary_id

69HCL23_0364

Identifier Type: -

Identifier Source: org_study_id