Clinical trial NCT05743400: Thymoglobulin® Pharmacokinetics in Patients Undergoing Hematopoietic Stem Cell Transplantation
Official title: Thymoglobulin® Pharmacokinetics for Graft-versus Host Disease in Children and Adults Undergoing Hematopoietic Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Hematopoietic Stem Cell Transplantation-Associated Thrombotic Microangiopathy
Keywords: Hematopoietic stem cell transplantation
Pharmacokinetics
HSCT
Anti-thymocyte globulin
Graft versus host disease
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2023-02-24
Enrollment: 35
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Thymoglobulin is widely applied as serotherapy in order to prevent acute graft-versus-host disease (GvHD) and graft rejection in patients undergoing non-Human Leukocyte Antigen (HLA)-identical hematopoietic stem cell transplantations (HSCT), with a delicate balance between prevention of GvHD and the promotion of immune reconstitution. Thymoglobulin is known as a drug with high pharmacokinetic (PK) variability. This variability influences drug exposure, which in turn determines the drug response of pharmacodynamics (PD). In order to maintain efficacy while reducing adverse effects of drugs across the entire age range, identification of the PK/PD relationships and the effect of growth and maturation on the different PK and PD parameters involved are crucial.

The investigators hypothesise that a better knowledge of Thymoglobulin PK and its covariates would help to individualise dosage regimen and would improve clinical outcomes, such as GvHD and immune reconstitution.

The investigators aim to build a population PK model of Thymoglobulin in order to study PK variability and its covariates. This model will help in optimizing dosage regimen in an individually way.


Eligibility criteria: Inclusion Criteria:

* Patient receiving Thymoglobulin therapy as part of a first HSCT
* Age ≥ 2 years
* Lansky or karnofsky score ≥ 50%.
* Enrolled in a social security plan
* Patient 18 years of age or older who is informed and has consented to participate in the study or minor patient whose parents/guardians have been informed and have given consent for the minor patient to participate in the study
* Female patients of childbearing potential must have an effective method of contraception (a pregnancy test will also be performed at inclusion).

Exclusion Criteria:

* Patient having received serotherapy (Thymoglobulin® or other) within 3 months before this HSCT
* Patient receiving another serotherapy during conditioning (Campath®)
* Patients with uncontrolled acute or chronic infections for which any form of immunosuppression would be contraindicated
* Known hypersensitivity to Thymoglobulin®.
* Pregnant or lactating women
* Patient participating simultaneously in another study of an investigational drug (no exclusion period)
* Patient under legal protection or deprived of liberty

Primary outcomes:
measure: Area under the concentration-time curve (AUC)
timeFrame: until elimination tf the drug (maximum 3 weeks post hematopoietic stem cell transplantation)
Secondary outcomes:
measure: Objective function value (OFV)
timeFrame: until elimination tf the drug (maximum 3 weeks post hematopoietic stem cell transplantation)
measure: Coefficient of variation of AUC
timeFrame: until elimination tf the drug (maximum 3 weeks post hematopoietic stem cell transplantation)
Other outcomes:
Locations:
city: Lyon
country: France
facility: Institut d'Hématologie et d'Oncologie Pédiatrique
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon Sud
Study officials:
References: