Thymoglobulin® Pharmacokinetics in Patients Undergoing Hematopoietic Stem Cell Transplantation (PHASAL-GA)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Hematopoietic Stem Cell Transplantation-Associated Thrombotic Microangiopathy
• Intervention / Treatment: Drug: Thymoglobulin 25 milligrams (mg) Injection; Biological: blood test

• Study Type: Interventional
• Enrollment (Estimated): 35
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Michael Philippe, MD, PhD; Phone Number: +33 0469166595; Email: michael.philippe@lyon.unicancer.fr
• Study Contact Backup: Name: Sylvain Goutelle, PU, PH; Email: sylvain.goutelle@chu-lyon.fr

Study Locations

• France
  • Lyon, France, 69008
    • Recruiting
    • Institut D'Hematologie Et D'Oncologie Pediatrique
    • Contact: Cécile RENARD, MD, PhD; Phone Number: +33 0469166570; Email: cecile.renard@ihope.fr
    • Principal Investigator: Cécile RENARD, MD, PhD
  • Pierre-Bénite, France, 69495
    • Recruiting
    • Centre Hospitalier Lyon Sud
    • Contact: Marie BALSAT, MD, PhD; Phone Number: +33 0478862240; Email: marie.balsat@chu-lyon.fr
    • Contact: Hélène LABUSSIERE-WALLET, MD, PhD; Phone Number: +33 0478862240; Email: helene.labussiere-wallet@chu-lyon.fr
    • Principal Investigator: Marie BALSAT, MD, PhD
    • Sub-Investigator: Hélène LABUSSIERE-WALLET, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective function value (OFV)	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	until elimination tf the drug (maximum 3 weeks post hematopoietic stem cell transplantation)
Coefficient of variation of AUC	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	until elimination tf the drug (maximum 3 weeks post hematopoietic stem cell transplantation)

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2023
• Primary Completion (Estimated): April 25, 2025
• Study Completion (Estimated): April 25, 2025

Study Registration Dates

• First Submitted: February 15, 2023
• First Submitted That Met QC Criteria: February 15, 2023
• First Posted (Actual): February 24, 2023

Study Record Updates

• Last Update Posted (Actual): September 29, 2023
• Last Update Submitted That Met QC Criteria: September 27, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Graft versus host disease; HSCT; Hematopoietic stem cell transplantation; Anti-thymocyte globulin
• Additional Relevant MeSH Terms: Hematologic Diseases; Thrombocytopenia; Blood Platelet Disorders; Thrombotic Microangiopathies; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Thymoglobulin
• Other Study ID Numbers: 69HCL21_1186; 2022-501594-39-00 (Other Identifier: EU-CT)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No