Impact of CMV-Specific Immune Reconstitution at the End of Letermovir Prophylaxis on the Development of Late Cytomegalovirus Infection in Hematopoietic Stem Cell Transplant Recipients (INMUNOEND)

NCT ID: NCT06814301

Last Updated: 2025-11-28

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Total Enrollment: 123 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-12-01
• Study Completion Date: 2027-09-30

Brief Summary

Cytomegalovirus (CMV) infection is a common complication in patients undergoing hematopoietic stem cell transplantation (SCT). Fixed-duration letermovir (LTV) prophylaxis during the first 100 days post-SCT is effective and safe in preventing this infection, although it may be associated with a delay in CMV-specific immune reconstitution. Hence, it is needed a study to evaluate whether the absence of CMV-specific immune reconstitution at the end of LTV prophylaxis is associated with the development of late infection. This could facilitate the individualization of CMV prophylaxis duration in these patients.

Methods and analysis: INMUNOEND is a multicenter, prospective, observational, non-interventional study including CMV seropositive patients undergoing allo-SCT who receive LTV prophylaxis during the first 100 days post-SCT. Immunological and virological monitorization will be conducted until day +200 post-SCT. The primary outcome variable is the percentage of patients who develop clinically significant CMV infection up to day +200 post-SCT after completing LTV prophylaxis. Data collected will include: baseline characteristics of the hematological diseases and comorbidities, variables related to SCT (i.e. engrafment, graft-versus-host disease, use of letermovir and CMV replication) and variables related to CMV-specific immune reconstitution.

Conditions

Cytomegalovirus Cell Mediated Immunity; Stem Cell Transplantation, Hematopoietic

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

patients undergoing allogenic-SCT who receive LTV prophylaxis with letermovir

Periodic immunological monitoring of CMV-specific immune reconstitution will be performed using QTF-CMV

Intervention Type: DIAGNOSTIC_TEST

A first determination will be made pre-HCT, followed by subsequent determinations at +30, +60, +90, +120, +150, +180, and +200 days post-HCT, as well as at the end of prophylaxis with Letermovir

Periodic immunological monitoring of CMV-specific immune reconstitution will be performed using QTF-CMV

Intervention Type: DIAGNOSTIC_TEST

A first determination will be made pre-HCT, followed by subsequent determinations at +30, +60, +90, +120, +150, +180, and +200 days post-HCT, as well as at the end of prophylaxis with LTV

Interventions

Periodic immunological monitoring of CMV-specific immune reconstitution will be performed using QTF-CMV

A first determination will be made pre-HCT, followed by subsequent determinations at +30, +60, +90, +120, +150, +180, and +200 days post-HCT, as well as at the end of prophylaxis with Letermovir

Intervention Type: DIAGNOSTIC_TEST

Periodic immunological monitoring of CMV-specific immune reconstitution will be performed using QTF-CMV

A first determination will be made pre-HCT, followed by subsequent determinations at +30, +60, +90, +120, +150, +180, and +200 days post-HCT, as well as at the end of prophylaxis with LTV

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• Age >18 years.
• CMV seropositivity (positive IgG) in the recipient at the time of SCT.
• First allogeneic hematopoietic stem cell transplant recipient (bone marrow, peripheral blood, or cord blood).
• Within the first 28 days post-SCT at the time of inclusion.
• Indication for LTV prophylaxis within the first 28 days post-transplant up to 100 days post-SCT, according to the criteria established in each center.

Exclusion Criteria

• CMV seronegativity (negative IgG) in the recipient at the time of transplant.
• Previous allogeneic stem cell transplant (patients with a prior autologous transplant are allowed to be included).
• History of CMV disease in the 6 months prior to inclusion.
• Need for preemptive therapy in the month prior to inclusion in the study.
• Received any of the following in the 14 days prior to inclusion: Ganciclovir, valganciclovir, foscarnet, acyclovir (at doses >3200 mg orally per day or >25 mg/kg IV per day), valacyclovir (at doses >3000 mg orally per day), famciclovir (at doses >1500 mg orally per day).
• Received any of the following in the 30 days prior to screening: Cidofovir, CMV hyperimmune immunoglobulin, any CMV antiviral in the investigational phase.
• Suspected or confirmed hypersensitivity reaction to the LTV formulation or any of its components.
• Severe hepatic insufficiency (defined as Child-Pugh class C).
• History of primary immunodeficiency prior to transplant.
• Participation in a clinical trial involving the administration of CMV vaccines, other investigational CMV drugs, or monoclonal antibodies.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Maimónides Biomedical Research Institute of Córdoba

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Hospital Universitario Reina Sofía

Córdoba, Córdoba, Spain

Countries

Spain

References

Caston JJ, Aparicio C, Paez-Vega A, Pozo Lopez L, Garcia E, Martin C, Ruiz-Arabi E, Cuesta-Casas MA, Bermudez-Rodriguez MA, Cerezo-Martin JM, Gonzalez-Sierra PA, Machuca I, Martin Dominguez FM, Saldana-Moreno R, Herrera C, Torre-Cisneros J. Impact of CMV-specific immune reconstitution at the end of letermovir prophylaxis on the development of late cytomegalovirus infection in haematopoietic stem cell transplant recipients (INMUNOEND): a protocol for a prospective, observational, multicentre study. BMJ Open. 2025 Oct 15;15(10):e101289. doi: 10.1136/bmjopen-2025-101289.

Reference Type: DERIVED

PMID: 41093321 (View on PubMed)

Other Identifiers

FCO-INM-2024-04

Identifier Type: -

Identifier Source: org_study_id