Thymoglobulin® Pharmacokinetics in Patients Undergoing Hematopoietic Stem Cell Transplantation

NCT ID: NCT05743400

Last Updated: 2024-09-19

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-09-25
• Study Completion Date: 2025-04-25

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.

Conditions

Hematopoietic Stem Cell Transplantation-Associated Thrombotic Microangiopathy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental treatment arm

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

Group Type: EXPERIMENTAL

Thymoglobulin 25 milligrams (mg) Injection

Intervention Type: DRUG

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.

blood test

Intervention Type: BIOLOGICAL

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: BIOLOGICAL

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

• Minimum Eligible Age: 2 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospices Civils de Lyon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Institut d'Hématologie et d'Oncologie Pédiatrique

Lyon, , France

Site Status: RECRUITING

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Michael Philippe, MD, PhD

Role: CONTACT

michael.philippe@lyon.unicancer.fr

0469166595 ext. +33

Sylvain Goutelle, PU, PH

Role: CONTACT

sylvain.goutelle@chu-lyon.fr

Facility Contacts

Cécile RENARD, MD, PhD

Role: primary

cecile.renard@ihope.fr

0469166570 ext. +33

Marie BALSAT, MD, PhD

Role: primary

marie.balsat@chu-lyon.fr

0478862240 ext. +33

Hélène LABUSSIERE-WALLET, MD, PhD

Role: backup

helene.labussiere-wallet@chu-lyon.fr

0478862240 ext. +33

Other Identifiers

2022-501594-39-00

Identifier Type: CTIS

Identifier Source: secondary_id

69HCL21_1186

Identifier Type: -

Identifier Source: org_study_id