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

Primary Purpose

Hematopoietic Stem Cell Transplantation-Associated Thrombotic Microangiopathy

Status
Recruiting
Phase
Phase 4
Locations
France
Study Type
Interventional
Intervention
Thymoglobulin 25 milligrams (mg) Injection
blood test
Sponsored by
Hospices Civils de Lyon
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hematopoietic Stem Cell Transplantation-Associated Thrombotic Microangiopathy focused on measuring Hematopoietic stem cell transplantation, Pharmacokinetics, HSCT, Anti-thymocyte globulin, Graft versus host disease

Eligibility Criteria

2 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Institut d'Hématologie et d'Oncologie PédiatriqueRecruiting
  • Centre Hospitalier Lyon SudRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Experimental treatment arm

Arm Description

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

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

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
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

Full Information

First Posted
February 15, 2023
Last Updated
September 27, 2023
Sponsor
Hospices Civils de Lyon
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1. Study Identification

Unique Protocol Identification Number
NCT05743400
Brief Title
Thymoglobulin® Pharmacokinetics in Patients Undergoing Hematopoietic Stem Cell Transplantation
Acronym
PHASAL-GA
Official Title
Thymoglobulin® Pharmacokinetics for Graft-versus Host Disease in Children and Adults Undergoing Hematopoietic Stem Cell Transplantation
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 25, 2023 (Actual)
Primary Completion Date
April 25, 2025 (Anticipated)
Study Completion Date
April 25, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospices Civils de Lyon

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematopoietic Stem Cell Transplantation-Associated Thrombotic Microangiopathy
Keywords
Hematopoietic stem cell transplantation, Pharmacokinetics, HSCT, Anti-thymocyte globulin, Graft versus host disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
35 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Experimental treatment arm
Arm Type
Experimental
Arm Description
Children over two years and adults undergoing a first hematopoietic stem cell transplantation will receiveThymoglobulin® as part of the conditioning.
Intervention Type
Drug
Intervention Name(s)
Thymoglobulin 25 milligrams (mg) Injection
Intervention Description
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
Biological
Intervention Name(s)
blood test
Intervention Description
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.
Primary Outcome Measure Information:
Title
Area under the concentration-time curve (AUC)
Description
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)
Time Frame
until elimination tf the drug (maximum 3 weeks post hematopoietic stem cell transplantation)
Secondary Outcome Measure Information:
Title
Objective function value (OFV)
Description
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
Time Frame
until elimination tf the drug (maximum 3 weeks post hematopoietic stem cell transplantation)
Title
Coefficient of variation of AUC
Description
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
Time Frame
until elimination tf the drug (maximum 3 weeks post hematopoietic stem cell transplantation)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Michael Philippe, MD, PhD
Phone
0469166595
Ext
+33
Email
michael.philippe@lyon.unicancer.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Sylvain Goutelle, PU, PH
Email
sylvain.goutelle@chu-lyon.fr
Facility Information:
Facility Name
Institut d'Hématologie et d'Oncologie Pédiatrique
City
Lyon
ZIP/Postal Code
69008
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cécile RENARD, MD, PhD
Phone
0469166570
Ext
+33
Email
cecile.renard@ihope.fr
First Name & Middle Initial & Last Name & Degree
Cécile RENARD, MD, PhD
Facility Name
Centre Hospitalier Lyon Sud
City
Pierre-Bénite
ZIP/Postal Code
69495
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marie BALSAT, MD, PhD
Phone
0478862240
Ext
+33
Email
marie.balsat@chu-lyon.fr
First Name & Middle Initial & Last Name & Degree
Hélène LABUSSIERE-WALLET, MD, PhD
Phone
0478862240
Ext
+33
Email
helene.labussiere-wallet@chu-lyon.fr
First Name & Middle Initial & Last Name & Degree
Marie BALSAT, MD, PhD
First Name & Middle Initial & Last Name & Degree
Hélène LABUSSIERE-WALLET, MD, PhD

12. IPD Sharing Statement

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Thymoglobulin® Pharmacokinetics in Patients Undergoing Hematopoietic Stem Cell Transplantation

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