Clinical trial NCT06814301: 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)
Official title: Impact of CMV-Specific Immune Reconstitution At the End of Letermovir Prophylaxis on the Development of Late Cytomegalovirus Infection in HSCT Recipients (INMUNOEND): a Protocol for a Prospective, Observational, Multicenter Study
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Cytomegalovirus Cell Mediated Immunity
Stem Cell Transplantation, Hematopoietic
Keywords: stem cell transplantation
cytomegalovirus
letermovir
prophylaxis
cytomegalovirus immunity
Lead sponsor: Maimónides Biomedical Research Institute of Córdoba
Sponsor class: OTHER
First posted: 2025-02-07
Enrollment: 123
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Consecutive CMV seropositive patients undergoing allogenic-SCT who receive LTV prophylaxis will be included. These patients will be prospectively evaluated during the first 200 days post-SCT.

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.


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.

Primary outcomes:
measure: percentage of patients who develop clinically significant CMV infection (CMV-Cs) up to day +200 post-SCT after completing LTV prophylaxis
timeFrame: From enrollment to 200 days post-SCT
Secondary outcomes:
measure: proportion of patients with CMV-specific immune reconstitution at each QTF-CMV measurement point
timeFrame: From enrollment to 200 days post-SCT
measure: proportion of patients with CMV replication during the 30 days following QTF-CMV testing
timeFrame: From enrollment to 200 days post-SCT
measure: detection of any CMV replication and maximum copy number (IU/mL) during follow-up
timeFrame: From enrollment to 200 days post-SCT
measure: percentage of patients without CMV-specific immune reconstitution at the end of LTV prophylaxis
timeFrame: From enrollment to 200 days post-SCT
Other outcomes:
Locations:
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofía
Study officials:
References: