Thymoglobulin® Pharmacokinetics in Patients Undergoing Hematopoietic Stem Cell Transplantation

Phase 4

Recruiting

• Conditions: Hematopoietic Stem Cell Transplantation-Associated Thrombotic Microangiopathy
• Interventions: Drug: Thymoglobulin 25 milligrams (mg) Injection; Biological: blood test

• Registration Number: NCT05743400
• Lead Sponsor: Hospices Civils de Lyon

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-02-15
• Study First Submitted QC: 2023-02-15
• Study First Posted: 2023-02-24
• Status Verified: 2023-09
• Study Start: 2023-09-25
• Last Update Submitted: 2023-09-27
• Last Update Posted: 2023-09-29
• Primary Completion: 2025-04-25
• Study Completion: 2025-04-25

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 35

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Experimental treatment arm	blood test	Children over two years and adults undergoing a first hematopoietic stem cell transplantation will receiveThymoglobulin® as part of the conditioning.
Experimental treatment arm	Thymoglobulin 25 milligrams (mg) Injection	Children over two years and adults undergoing a first hematopoietic stem cell transplantation will receiveThymoglobulin® as part of the conditioning.

Primary Outcome Measures

Name	Time	Method
Area under the concentration-time curve (AUC)	until elimination tf the drug (maximum 3 weeks post hematopoietic stem cell transplantation)	Measure of the Thymoglobulin® exposure by the PK criteria : Area under the concentration-time curve (AUC) .; AUC is measured by day since the first day of Thymoglobulin infusion during conditioning (day 0) until elimination tf the drug. AUC is expressed as milligrams/hour/Liter. (mg/h/L)

Secondary Outcome Measures

Name	Time	Method
Objective function value (OFV)	until elimination tf the drug (maximum 3 weeks post hematopoietic stem cell transplantation)	Comparison of the OFV of different build population pharmacokinetic models based on results of pharmacokinetic analysis, from start of thymoglobulin® infusion until elimination of the drug
Coefficient of variation of AUC	until elimination tf the drug (maximum 3 weeks post hematopoietic stem cell transplantation)	Ratio of typical variation of AUC to the mean AUC. AUC is measured by day since the first day of Thymoglobulin infusion during conditioning (day 0) until elimination of the drug

Trial Locations

Locations (2)

Institut d'Hématologie et d'Oncologie Pédiatrique; 🇫🇷 Lyon, France

Centre Hospitalier Lyon Sud; 🇫🇷 Pierre-Bénite, France