Evaluation of Antiviral Prophylaxis with Cytolytic T Lymphocytes for Cytomegalovirus Infection in HLA-Identical Familial Hematopoietic Stem Cell Transplantation

The primary objective of this clinical trial is to evaluate the **efficacy** of antiviral prophylaxis using specific cytolytic T lymphocytes (CTLs) against **cytomegalovirus (CMV)** in reducing the incidence of CMV infection at 100 days post-transplant. This is assessed in comparison to historical controls from the haematology service of the Hospital Universitario Marqués de Valdecilla. The clinical relevance of this objective lies in its potential to provide an effective prophylactic strategy for patients undergoing HLA-identical familial allogeneic hematopoietic stem cell transplantation, who currently lack specific pharmacological prophylaxis options.

Secondary objectives include: - Assessing the need for CMV treatment and evaluating the incidence, characteristics, and mortality associated with CMV disease. - Evaluating the occurrence of immediate or delayed infusional reactions, and the incidence and severity of adverse events (AEs) and serious adverse events (SAEs), including acute and chronic graft-versus-host disease (GVHD) and overall mortality. - Exploratory objectives involve evaluating the persistence of allogeneic CMV-specific memory T lymphocytes and post-HAPLO immune reconstitution at specified intervals post-transplant.

The clinical trial involves participants who are adult patients, aged over 18 years, diagnosed with or without hematologic malignancy, and have undergone an allogeneic hematopoietic stem cell transplant (**HSCT**) from **HLA-identical** family donors. The study population includes both male and female subjects, and it does not involve a vulnerable population. Participants are required to have a partial recovery of the hematopoietic implant, indicated by an absolute neutrophil count greater than 0.5 x10^9 cells/L for at least three consecutive post-HSCT determinations. The trial does not specify the total number of participants, as the sponsor has not provided this information. Lifestyle considerations such as diet and physical activity are not detailed in the available data. Key inclusion criteria include the requirement for donors to be **CMV seropositive** and the exclusion of candidates eligible to receive Letermovir. The trial aims to evaluate the efficacy of antiviral prophylaxis with specific cytotoxic T lymphocytes against **cytomegalovirus** infection in reducing its incidence at 100 days post-transplant.

The clinical trial is designed to evaluate the **efficacy** of antiviral prophylaxis using specific cytolytic T lymphocytes (CTLs) against **cytomegalovirus (CMV) infection** in patients who have undergone allogeneic hematopoietic stem cell transplantation (HSCT) from HLA-identical family donors. This is a Phase II trial, characterized by a randomized, double-blind, and controlled design, aimed at reducing the incidence of CMV infection within 100 days post-transplantation. The trial is expected to run from March 26, 2022, to February 23, 2025, with participant involvement lasting approximately 100 days post-transplantation.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on specific criteria, such as being over 18 years of age, having received an allogeneic HSCT, and having a CMV seropositive donor. The screening will also include a negative pregnancy test for women and the signing of informed consent by both the patient and the donor. Follow-up visits will be scheduled to monitor the incidence of CMV infection, assess the need for CMV treatment, and evaluate the presence of allogeneic CMV-specific memory T lymphocytes. The end-of-study visit will occur at the 100-day mark post-transplantation to determine the primary endpoint, which is the incidence of CMV infection, measured by viral load.

Participants may be terminated early from the study if they do not meet the inclusion criteria, experience adverse effects, or withdraw consent. The trial will utilize an injection route for the administration of the investigational product, which is not a pediatric formulation. The study aims to provide valuable insights into the prophylactic use of CTLs in preventing CMV infection in a specific patient population, contributing to the broader understanding of antiviral strategies in post-transplant care.

The clinical trial involves the use of an **experimental medication** classified under the ATC code J05AX, which pertains to **other antivirals**. The pharmaceutical form of the medication is designated as PHF00082MIG. The medication is administered via **injection**. The specific dosage, frequency of administration, and maximum daily or total dose amounts are not specified in the available data. The medication is not a pediatric formulation and is not classified as an orphan drug. The active substance name and product name are not provided in the trial data.

The trial does not specify any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatment. The primary objective of the trial is to evaluate the efficacy of antiviral prophylaxis using specific **cytolytic T lymphocytes (CTLs)** against **cytomegalovirus (CMV)** in reducing the incidence of CMV infection at 100 days post-transplant in patients undergoing HLA-identical familial allogeneic hematopoietic stem cell transplantation. The trial does not include specific information on dosing schedules or participant compliance monitoring. The study is conducted without specific pharmacological prophylaxis available for the participants.

The efficacy of the antiviral prophylaxis in the clinical trial will be assessed by evaluating the incidence of **Cytomegalovirus (CMV)** infection at 100 days post-transplant. The primary endpoint is defined as the occurrence of CMV infection, measured by a viral load greater than 200 copies in two determinations or greater than 1000 in one determination using quantitative PCR (PCRq). Secondary endpoints include assessing the need for CMV treatment, evaluating the incidence of CMV disease, and assessing the presence of allogeneic CMV-specific memory T lymphocytes. These efficacy parameters will be collected and analyzed at the specified timepoint of 100 days post-transplant to determine the effectiveness of the prophylactic intervention.