IDEAL: Thymoglobulin® Pharmacokinetics in Patients Undergoing Hematopoietic Stem Cell Transplantation

Sponsor

Hospices Civils de Lyon (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05743400

Collaborator

(none)

Enrollment

Locations

Arm

19.3

Anticipated Duration (Months)

17.5

Patients Per Site

0.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hematopoietic Stem Cell Transplantation-Associated Thrombotic Microangiopathy	Drug: Thymoglobulin 25 milligrams (mg) Injection Biological: blood test	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

35 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Thymoglobulin® Pharmacokinetics for Graft-versus Host Disease in Children and Adults Undergoing Hematopoietic Stem Cell Transplantation

Anticipated Study Start Date :

Jul 1, 2023

Anticipated Primary Completion Date :

Feb 8, 2025

Anticipated Study Completion Date :

Feb 8, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental treatment arm Children over two years and adults undergoing a first hematopoietic stem cell transplantation will receiveThymoglobulin® as part of the conditioning.	Drug: Thymoglobulin 25 milligrams (mg) Injection Patients will receive thymoglobulin between 5 and 20 milligrams/kilograms (mg/kg) as an intravenous infusion over a period of 2 to 5 days depending on the dose and the transplant package chosen by the physician. Biological: blood test Thymoglobulin® serum levels Time frame : samples will be drawn at the following points : 1 after each end of perfusion ; 1 though concentration before each perfusion ; 3 blood samples in 3 different days during the first week; 1 weekly for 2 weeks post HSCT.

Arm

Intervention/Treatment

Experimental: Experimental treatment arm

Children over two years and adults undergoing a first hematopoietic stem cell transplantation will receiveThymoglobulin® as part of the conditioning.

Drug: Thymoglobulin 25 milligrams (mg) Injection

Patients will receive thymoglobulin between 5 and 20 milligrams/kilograms (mg/kg) as an intravenous infusion over a period of 2 to 5 days depending on the dose and the transplant package chosen by the physician.

Biological: blood test

Thymoglobulin® serum levels Time frame : samples will be drawn at the following points : 1 after each end of perfusion ; 1 though concentration before each perfusion ; 3 blood samples in 3 different days during the first week; 1 weekly for 2 weeks post HSCT.

Outcome Measures

Primary Outcome Measures

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

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
Proportion of patients within the therapeutic range [until elimination tf the drug (maximum 3 weeks post hematopoietic stem cell transplantation)]
Percentage of patients with an estimated AUC with the 75-95 mg/h/L therapeutic range, from start of thymoglobulin® infusion until elimination of the drug

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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