Clinical Research Directory

Prehabilitation for Patients Diagnosed With Blood Cancer and Treated With Al-logeneic Hematopoietic Stem Cell Transplantation

Seventy-five percent of patients treated with hematopoietic stem cell transplants survive one-year post-transplantation. However, this intensive treatment is associated with prolonged hospitalizations and significant deconditioning. Pathophysiological changes in skeletal muscle mass and function have notable implications for disease progression and long-term prognosis. Patients frequently report substantial rehabilitation needs, though these needs are highly individualized and fluctuate over time, with musculoskeletal dysfunction and fa-tigue being the most common barriers to prehabilitation. Furthermore, at least 35% of cancer patients are found to have inadequate daily protein intake, which may hinder improve-ments in physical performance through prehabilitation. Several recent studies have demonstrated the safety and feasibility of exercise-based prehabilitation interventions during the pre-transplant period. However, no full-scale randomized controlled trial (RCT) has been conducted to date.

VIROMARKERS GA n.101194735 - CMV and TTV Biomarkers Study Protocol

The study is one of the researches carried out in the VIROMARKERS Project. The project VIROMARKERS is supported by the Innovative Health Initiative Joint Undertaking (IHI JU) under grant agreement No 101194735. The JU receives support from the European Union's Horizon Europe research and innovation programme and COCIR, EFPIA, Europa Bio, MedTech Europe, Vaccines Europe, and Roboscreen. To date, the virological surveillance for CMV replication relies basically on the quantification of CMV-DNA in blood or plasma by using Real-Time PCR assays, and CMV-DNAemia is known to correlate with both CMV-related disease and non-relapse mortality \[Ljungman, 2025\]. However, the detection of CMV-DNAemia is not always associated with an active CMV replication, particularly in patients exposed to letermovir. Therefore, the identification of new virological markers to accurately monitor CMV activity in the early and late post-HSCT phases, remains a crucial issue especially in individuals receiving letermovir as prophylaxis to ensure a proper diagnosis of CMV infection/disease and to guide prophylactic and pre-emptive antiviral treatment. In this setting, the quantification of CMV-RNA represents a potential candidate marker capable of better reflecting the presence of complete, infectious CMV virions than CMV-DNAemia. Despite several data support a correlation of CMV UL21.5-mRNA with viral activity \[Nicastro, 2025\], studies investigating the kinetics of this viral mRNA among immune-suppressed patients at risk of CMV re-uptake are largely missing, especially in the setting of patients receiving antiviral prophylaxis with letermovir after HSCT. TTV-DNA load was mostly investigated in solid organ transplant patients (SOT), where it showed a good correlation of high viral load and degree of immunosuppression. In HSCT patients the interaction of the immune system, which is under reconstitution, and clinically relevant CMV infection is more complex. First data have been reported by our group \[Gilles et al., 2017\] showing high TTV load as a prognostic marker for risk of complications after HSCT. Little information is available for HSCT patients under letermovir prophylaxis. Specific primary objectives related to CMV monitoring in the HSCT setting are the following: Primary In participants who received HSCT, to estimate the rate of initiation of anti-CMV therapy during letermovir-based prophylaxis and the rate of CMV re-activation (based on symptoms, signs of organ dysfunction and CMV-DNAemia) after suspension of letermovir. To evaluate the kinetics of CMV-RNAemia, CMV-DNAemia and TTV-DNAemia and their correlation during prophylaxis with letermovir. To establish whether early quantitative CMV-RNA level or the early kinetics of CMV-RNAemia and TTV-DNAemia during prophylaxis can predict initiation of anti-CMV therapy. In participants not initiating anti-CMV therapy during prophylaxis, to establish whether quantitative CMV-RNA level at time of letermovir suspension or the kinetics of CMV-RNAemia and TTV-DNAemia during prophylaxis can predict CMV re-activation (based on symptoms signs of organ dysfunction and CMV-DNAemia) after suspension of letermovir. Secondary objectives include to establish a cut-off for CMV-RNAemia and TTV DNAemia to maximize the accuracy of prediction of CMV re-activation after suspension of prophylaxis; to explore the kinetics of CMV-RNAemia and TTV-DNAemia in participants treated with anti CMV drugs. The information used from this study on participants in the HSCT setting will be rapidly analyzed and shared broadly to guide policymakers for the use and monitoring of CMV-DNAemia, CMV-RNAemia and TTV-DNAemia in CMV disease and to design future studies. For exact plans regarding the expected date of study completion and plans for dissemination please refer to separate documents produced within the WP5 of VIROMARKERS.

Donor Virus-Specific CMV or AdV CTL to Treat CMV or AdV Reactivation or Disease After Solid Organ or HCT

This trial studies the side effects and how well allogeneic cytomegalovirus-specific cytotoxic T lymphocytes (donor cytomegalovirus \[CMV\] specific cytotoxic T-lymphocytes \[CTLs\]) or allogeneic adenovirus-specific cytotoxic T lymphocytes (donor adenovirus-specific \[AdV\] specific CTLs) work in treating CMV or AdV reactivation or infection in participants who have undergone stem cell transplant or solid organ transplant. White blood cells from donors may be able to kill cancer cells in patients with cytomegalovirus or adenovirus that has come back after a stem cell or solid organ transplant.

Naive T Cell Depletion for Preventing Chronic Graft-versus-Host Disease in Children and Young Adults With Blood Cancers Undergoing Donor Stem Cell Transplant

This phase II trial studies how well naive T-cell depletion works in preventing chronic graft-versus-host disease in children and young adults with blood cancers undergoing donor stem cell transplant. Sometimes the transplanted white blood cells from a donor attack the body's normal tissues (called graft versus host disease). Removing a particular type of T cell (naive T cells) from the donor cells before the transplant may stop this from happening.

High Dose Vitamin A in Preventing Gastrointestinal GVHD in Participants Undergoing Donor Stem Cell Transplant

This phase I trial studies the side effects and how well high dose vitamin A works in preventing gastrointestinal graft versus host disease (GVHD) in participants undergoing donor stem cell transplant. Vitamin A deficiency is associated with increased risk of gastrointestinal GVHD. Vitamin A regulates growth and differentiation of intestinal cells and may reduce risk of gastrointestinal GVHD.