Clinical trial NCT06080490: Tacrolimus Blood Concentration and Transplant-related Outcomes in Pediatric HSCT Recipients
Official title: Factors Affecting the Tacrolimus Blood Concentration and Its Impact on Transplant-related Outcomes in Pediatric HSCT Recipients: a Single-center Retrospective Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Graft Vs Host Disease
Transplant Failure
Stem Cell Transplant Complications
Keywords: HSCT
Tacrolimus
GVHD
Pediatric patients
Lead sponsor: University of Pisa
Sponsor class: OTHER
First posted: 2023-10-12
Enrollment: 125
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients who underwent allo-HSCT procedure between January 2011and December 2022 at IRCC Burlo Garofolo

Brief summary: The goal of this retrospective observational study is to investigate any possible association among tacrolimus (TAC) blood concentrations, clinical efficacy and tolerability.

Therefore, the main questions it aims to answer are:

1. to clarify which variables, how and to what extent influence daily TAC blood concentrations in pediatric allo-hematopoietic stem cell transplantation (HSCT) recipients;
2. to investigate the incidence of graft-versus-host disease (GVHD) and graft failure according to TAC exposure.

Pediatric patients administered TAC to prevent GVHD after an allogeneic bone marrow transplantation.

Detailed description: Patients undergoing allo-HSCT will be recruited at IRCC Burlo Garofolo, collecting demographic and clinical characteristics from electronic medical records in a retrospective manner: age, sex, primary disease, donor type and stem cell source, body weight (BW), white blood cell (WBC) count, platelet count, red blood cell (RBC) counts, hemoglobin (HGB) and hematocrit (HCT) levels, red cell concentrate (RCC) transfusions. Other clinical laboratory data (i.e., liver and kidney function) will be included, as well as concomitant drugs administered to patients after allo-HSCT (i.e, mycophenolate mofetil, steroids, pantoprazole, voriconazole, methotrexate). Data will be collected, validated, and presented according to Good Clinical Practice (GCP) principles to support the statistical analyses and subsequent reporting. Once selected according to predefined inclusion requirements, data will be collected anonymously; an identification code will be assigned to each case. As per GCP, all collected information will be recorded, handled, and stored in a way that allows its accurate reporting, interpretation, and verification with user access restriction, and data will be retrievable by designated personnel only.

Because of the retrospective nature of the present research protocol, all eligible patients will be included in the study population only if their medical and laboratory records will be complete.

Statistical analyses (for descriptive and comparative aims) will be performed stratifying patients by body weight, age, gender, and source of stem cells. Univariate and multivariate tests will be used, together with Kaplan-Meyer tes, Cox proportional hazard model and ROC curve analysis.

Eligibility criteria: Inclusion Criteria:

* Age of the patients between 0 and 18 years (pediatric)
* Patients undergoing allogeneic bone marrow transplantation
* Patients' GVHD prophylaxis with tacrolimus
* Signed informed consent

Exclusion Criteria:

* Patients undergoing autologous bone marrow transplantation
* Patients not undergoing GVHD prophylaxis
* Patients undergoing cyclosporin prophylaxis
* Incomplete pharmacokinetic/pharmacodynamic data
* Lack of any informed consent

Primary outcomes:
measure: TAC pharmacokinetics
timeFrame: 0-30 days
Secondary outcomes:
measure: GVHD
timeFrame: 0-180 days
measure: Graft failure
timeFrame: 0-180 days
Other outcomes:
Locations:
city: Trieste
country: Italy
facility: IRCCS Burlo Garofolo
Study officials:
affiliation: IRCCS Burlo Garofolo - Trieste - ITALY
name: Natalia Maximova, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Braidotti S, Curci D, Maestro A, Zanon D, Maximova N, Di Paolo A. Effect of early post-hematopoietic stem cell transplant tacrolimus concentration on transplant outcomes in pediatric recipients: One facility's ten-year experience of immunosuppression with tacrolimus. Int Immunopharmacol. 2024 Sep 10;138:112636. doi: 10.1016/j.intimp.2024.112636. Epub 2024 Jul 10.