- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02048800
Treosulfan Pharmacokinetics in Children Undergoing Allogeneic HSCT (TreoPK)
Evaluation of Treosulfan Pharmacokinetics (PK) in Children Undergoing Allogeneic Haematopoietic Stem Cell Transplantation (HSCT)
Every year around 70 children affected by cancer or life-threatening genetic diseases undergo haematopoietic cell transplantation (HCT) within the Blood and Marrow Transplant (BMT) unit at Great Ormond Street Hospital (GOSH).
One of the main goals of the BMT unit over the last decade has been to reduce the morbidity and mortality related to HCT, and the group has become a world-leader in pioneering less toxic transplants.
Fixed high doses of chemotherapy drugs are generally used to prepare children for HCT but several studies have shown a correlation between the concentration of these drugs achieved in the patient's blood, and the success or failure of the HCT procedure.
Recently a new drug, Treosulfan, has become available for use in patients undergoing HCT, and GOSH has pioneered its introduction in children undergoing HCT. With promising early results, Treosulfan has become the pre-HCT drug of choice, however, very little is currently known about how the drug is metabolised and cleared from the body, particularly in children.
The investigators therefore plan to investigate the pharmacokinetic (PK) profile of Treosulfan in children undergoing HCT at GOSH and define which parameters affect its metabolism and clearance, and what blood levels are associated with a favourable outcome (graft take without toxicity) or a poor result (graft rejection and/or toxicity).
Study Overview
Status
Intervention / Treatment
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
-
-
-
London, United Kingdom, WC1N 3JH
- Great Ormond Street Hospital for Children
-
Newcastle Upon Tyne, United Kingdom, NE1 4LP
- Great North Childrens Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- age ≥ 28 days and ≤ 18 years old;
- Karnofsky Performance Status ≥ 50 or Lansky Performance Status ≥ 30;
- provide signed, written informed consent from parent or guardian;
- be able to comply with study procedures and follow-up examinations;
- have adequate organ function (as indicated by Table 1, page 27), within 14 days prior enrollment;
- negative pregnancy test in post-pubertal female patients.
Exclusion Criteria:
- patients aged < 28 days and > 18 years old;
- patients with compromised organ function*;
- patients with any other severe concurrent disease, which, in the judgment of the Investigator, would make the patient inappropriate for entry into this study;
- known hypersensitivity to Treosulfan or Fludarabine;
- pregnancy/lactation.
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Treosulfan PK
Children with indication to HSCT receiving Treosulfan
|
Treosulfan will be administered over 3 days prior to HSCT at the following dose: 10 g/m2 (children aged < 3months) or 12 g/m2 (children aged 3/12 months) or 14 g/m2 (children aged > 12 months)
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
1) Assess maximum concentration (Cmax) after Treosulfan infusion in children prior to allogeneic haematopoietic stem cell transplantation.
Time Frame: day -7 and day -5 pre HSCT
|
day -7 and day -5 pre HSCT
|
2) Assess half life after Treosulfan infusion in children prior to allogeneic haematopoietic stem cell transplantation.
Time Frame: Day -7 and day-5 pre HSCT
|
Day -7 and day-5 pre HSCT
|
3) Assess the area under the curve (AUC) after Treosulfan infusion in children prior to allogeneic haematopoietic stem cell transplantation.
Time Frame: Day -7 and day -5 pre HSCT
|
Day -7 and day -5 pre HSCT
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
1) Assess interindividual and intraindividual variability of PK parameters in children of different age and weight;
Time Frame: day -7 and -5 pre HSCT
|
To measure Treosulfan PK parameteres such as maximum concentration, area under the curve and half life after the first (day -7) and third (day -5) dose of Treosulfan and study if there is any significant intrapatient and interpatient variability of these results.
|
day -7 and -5 pre HSCT
|
2) Assess the relationship between PK parameters and patient characteristics;
Time Frame: day -7 and -5 pre HSCT
|
To study the relationship between treosulfan PK parameters such as area under the curve, maximum concentration and half life after the 1st and 3rd administration and pre-HSCT parameters such as renal function (creatinine, urea levels) and liver function (ALT, AST, GGT, bilirubin).
|
day -7 and -5 pre HSCT
|
3) Assess the relationship between Treosulfan PK and regimen related toxicity (using the NCI toxicity criteria scoring system) and survival;
Time Frame: from day -7 pre HSCT to day +100 post HSCT
|
The toxicity of the transplant will be recorded in the clinical notes and CRF forms using the NCI toxicity criteria (toxicity score for every organ/system, with a range from 1 to 5).
This information will be correlated to Treosulfan PK criteria such as maximum concentration and area under the curve
|
from day -7 pre HSCT to day +100 post HSCT
|
4) Assess the relationship between Treosulfan PK and efficacy parameters, such as rate of engraftment and donor chimerism.
Time Frame: from day -7 pre HSCT to day + 360 post HSCT
|
Donor engraftment in the peripheral blood (in different cell lineages: CD15+ cells and CD3+ cells) will be addressed regularly after HSCT and these results will be correlated with Treosulfan PK parameters such as area under the curve.
|
from day -7 pre HSCT to day + 360 post HSCT
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Robert Chiesa, MD, Great Ormond Street Hospital, London, UK
- Principal Investigator: Mary Slatter, MD, Great North Childrens Hospital, Newcastle upon Tyne, UK
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 10MI28
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Allogeneic Haematopoietic Stem Cell Transplantation
-
University of ManchesterThe Christie NHS Foundation TrustRecruitingHaematopoietic Stem Cell TransplantationUnited Kingdom
-
University Hospital, GenevaRecruitingAllogeneic Hematopoietic Stem Cell Transplantation | Hematopoietic Stem Cell Transplantation | Autologous Hematopoietic Stem Cell TransplantationSwitzerland
-
Medical University of GrazCompletedAllogeneic Stem Cell Transplantation
-
University of ZurichCompletedAllogeneic Stem Cell TransplantationSwitzerland
-
Pierrel Research Europe GmbHRoche Pharma AGTerminatedAllogeneic Stem Cell TransplantationAustria, Germany, Spain
-
H. Kim LyerlyNational Cancer Institute (NCI); National Institutes of Health (NIH)TerminatedAllogeneic Stem Cell TransplantationUnited States
-
Mitchell Horwitz, MDPfizerTerminatedAllogeneic Stem Cell TransplantationUnited States
-
IRCCS Azienda Ospedaliero-Universitaria di BolognaCompletedGVHD | Allogeneic Stem Cell TransplantationItaly
-
Sidney Kimmel Cancer Center at Thomas Jefferson...National Cancer Institute (NCI)TerminatedALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATIONUnited States
-
Universitaire Ziekenhuizen KU LeuvenUnknownHematopoietic Stem Cell Transplantation | Hematopoietic Stem Cell Transplantation, Allogeneic
Clinical Trials on Treosulfan
-
Sheba Medical CenterUnknownHodgkin Lymphoma | Non Hodgkin LymphomaIsrael
-
IRCCS San RaffaeleUnknownLeukemia | Multiple Myeloma | Hodgkin Lymphoma | Chronic Lymphocytic Leukemia | Chronic Myeloid Leukemia | Myelodysplastic Syndrome | Diffuse Large Cell LymphomaItaly
-
Hospices Civils de LyonUnknownHematological Malignancies | Allogeneic TransplantationFrance
-
OHSU Knight Cancer InstituteNational Cancer Institute (NCI); medac GmbHCompletedMyelodysplastic Syndromes | LeukemiaUnited States
-
IRCCS San RaffaeleTerminatedMultiple Myeloma | Graft Vs Host Disease | Leukemia, Acute | Transplant-Related Hematologic Malignancy | Irradiated Bone MarrowItaly
-
Dr. Avichai Shimoni MDCompletedAcute Myeloid Leukemia | Myelodysplastic SyndromeIsrael
-
medac GmbHSyneos Health; Celerion; Venn Life SciencesCompletedBone Marrow Failure Syndromes | Inborn Errors of Metabolism | Primary Immunodeficiencies | HaemoglobinopathiesPoland, Czechia, Germany, Italy
-
medac GmbHCompleted
-
Center for International Blood and Marrow Transplant...National Marrow Donor Program; Pediatric Blood and Marrow Transplant Consortium and other collaboratorsCompletedAcute Myeloid Leukemia (AML) | Myelodysplastic Syndrome (MDS)United States
-
medac GmbHCompleted