Hematopoietic Stem Cell Transplantation-Associated Thrombotic MicroangiopathyPhase 4PHASAL-GANCT05743400
Thymoglobulin® Pharmacokinetics in Patients Undergoing Hematopoietic Stem Cell Transplantation
A Phase 4 study testing Thymoglobulin 25 milligrams (mg) Injection and blood test in people with Hematopoietic Stem Cell Transplantation-Associated Thrombotic Microangiopathy, run by Hospices Civils de Lyon at 2 sites in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- Hematopoietic Stem Cell Transplantation-Associated Thrombotic Microangiopathy
- What is being tested?
- Thymoglobulin 25 milligrams (mg) Injection and blood test
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 2 sitesFrance
- Study dates
- 25 Sep 2023to 25 Apr 2025
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
Sylvain Goutelle, PU, PH contact
France2 sites, 2 recruiting
- Recruiting
Institut d'Hématologie et d'Oncologie Pédiatrique
Lyon, 69008
Cécile RENARD, MD, PhD, 0469166570 ext. +33, cecile.renard@ihope.fr
Cécile RENARD, MD, PhD
- Recruiting
Centre Hospitalier Lyon Sud
Pierre-Bénite, 69495
Marie BALSAT, MD, PhD, 0478862240 ext. +33, marie.balsat@chu-lyon.fr
Hélène LABUSSIERE-WALLET, MD, PhD, 0478862240 ext. +33, helene.labussiere-wallet@chu-lyon.fr
About this study
Official title: 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.
- Being tested
- Thymoglobulin 25 milligrams (mg) Injection, blood test
- Keywords
- Hematopoietic stem cell transplantation, Pharmacokinetics, HSCT, Anti-thymocyte globulin, Graft versus host disease
- Medical subject headings
- Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Thymoglobulin 25 milligrams (mg) InjectionDrug
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 testBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| Experimental treatment arm | Experimental | Children over two years and adults undergoing a first hematopoietic stem cell transplantation will receiveThymoglobulin® as part of the conditioning. Receives: Drug: Thymoglobulin 25 milligrams (mg) Injection; Biological: blood test |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: until elimination tf the drug (maximum 3 weeks post hematopoietic stem cell transplantation)
Secondary outcomes (2)
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
Measured: 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
Measured: until elimination tf the drug (maximum 3 weeks post hematopoietic stem cell transplantation)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2023
- Study start25 Sep 2023
- Primary completion25 Apr 2025 (estimated)
- Study completion25 Apr 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hematopoietic Stem Cell Transplantation-Associated Thrombotic MicroangiopathyStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05743400
- Sponsor's protocol ID
- 69HCL21_1186
- Other IDs
- 2022-501594-39-00
- Acronym
- PHASAL-GA
- Status last verified
- Sep 2024
- First submitted
- 15 Feb 2023
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Thymoglobulin® Pharmacokinetics for Graft-versus Host Disease in Children and Adults Undergoing Hematopoietic Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT05743400
- Acronym / sponsor ID
- PHASAL-GA / 69HCL21_1186
- Keywords
- Hematopoietic stem cell transplantation, Pharmacokinetics, HSCT, Anti-thymocyte globulin, Graft versus host disease
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 35 participants (estimated)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- 25 Sep 2023 (actual)
- Primary completion
- 25 Apr 2025 (estimated)
- Study completion
- 25 Apr 2025 (estimated)
- First posted
- 24 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental treatment arm | Experimental | Drug: Thymoglobulin 25 milligrams (mg) Injection, Biological: blood testChildren over two years and adults undergoing a first hematopoietic stem cell transplantation will receiveThymoglobulin® as part of the conditioning. |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Thymoglobulin 25 milligrams (mg) InjectionPatients 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. | Drug | Experimental treatment arm |
| blood testThymoglobulin® 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. | Biological | Experimental treatment arm |
Primary outcome
Area under the concentration-time curve (AUC)
Time frame: 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)
2 secondary outcomes
Objective function value (OFV)
Time frame: until elimination tf the drug (maximum 3 weeks post hematopoietic stem cell transplantation)
Coefficient of variation of AUC
Time frame: until elimination tf the drug (maximum 3 weeks post hematopoietic stem cell transplantation)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
Related trials for Hematopoietic Stem Cell Transplantation-Associated Thrombotic Microangiopathy
Not yet recruitingObservational study
Assessing the Incidence of Transplant Associated Thrombotic Microangiopathy (TA-TMA) in Adult Patients Undergoing Allogeneic Stem Cell Transplant (SCT)
Transplant Associated Microangiopathy TAM, Transplant Complication
Recruiting
Safety and Efficacy of Iptacopan in Patients With High-Risk Transplantation-Associated Thrombotic Microangiopathy
Thrombotic Microangiopathy, Hematopoietic Stem Cell Transplantation (HSCT)
RecruitingPhase 2
Safety and Efficacy of Eculizumab in High-risk TA-TMA
Transplant-Associated Thrombotic Microangiopathy (TA-TMA)
RecruitingObservational study
Identification of Plasma Biomarkers for Early Diagnosis of Transplant-associated Thrombotic Microangiopathy
Thrombotic Microangiopathies, Hematopoietic Stem Cell Transplantation
RecruitingObservational study
Thrombotic Microangiopathy (TMA) Associated With Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) In Adult Patients
Thrombotic Microangiopathy
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sylvain Goutelle, PU, PH contact
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Thymoglobulin 25 milligrams (mg) Injection and blood test in people with Hematopoietic Stem Cell Transplantation-Associated Thrombotic Microangiopathy, run by Hospices Civils de Lyon at 2 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Michael Philippe, MD, PhD (0469166595 ext. +33, michael.philippe@lyon.unicancer.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area under the concentration-time curve (AUC) (time frame: until elimination tf the drug (maximum 3 weeks post hematopoietic stem cell transplantation)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.