Thymoglobulin® Pharmacokinetics in Patients Undergoing Hematopoietic Stem Cell Transplantation

NCT05743400 | Recruiting Phase 4

• 2 other identifiers: 69HCL21_11862022-501594-39-00
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 2

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

Keywords

Hematopoietic stem cell transplantation; Pharmacokinetics; HSCT; Anti-thymocyte globulin; Graft versus host disease

Outcome Measures

Primary Outcomes (1)

• Area under the concentration-time curve (AUC)

  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)

  until elimination tf the drug (maximum 3 weeks post hematopoietic stem cell transplantation)

Secondary Outcomes (2)

• Objective function value (OFV)

  until elimination tf the drug (maximum 3 weeks post hematopoietic stem cell transplantation)

• Coefficient of variation of AUC

  until elimination tf the drug (maximum 3 weeks post hematopoietic stem cell transplantation)

Study Arms (1)

Experimental treatment arm

EXPERIMENTAL

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; Biological: blood test

Interventions

Thymoglobulin 25 milligrams (mg) Injection 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.

Experimental treatment arm

blood test 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.

Experimental treatment arm

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 under legal protection or deprived of liberty

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (2)

Institut d'Hématologie et d'Oncologie Pédiatrique

Lyon, 69008, France

RECRUITING

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

RECRUITING

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

Injections; Hematologic Tests

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Central Study Contacts

Michael Philippe, MD, PhD

CONTACT

0469166595; michael.philippe@lyon.unicancer.fr

Sylvain Goutelle, PU, PH

CONTACT

sylvain.goutelle@chu-lyon.fr

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2023
• First Posted: February 24, 2023
• Study Start: September 25, 2023
• Primary Completion: April 25, 2025
• Study Completion: April 25, 2025
• Last Updated: September 19, 2024

Record last verified: 2024-09

Locations

FR (2)