Clinical trial NCT02048800: Treosulfan Pharmacokinetics in Children Undergoing Allogeneic HSCT
Official title: Evaluation of Treosulfan Pharmacokinetics (PK) in Children Undergoing Allogeneic Haematopoietic Stem Cell Transplantation (HSCT)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Allogeneic Haematopoietic Stem Cell Transplantation
Keywords: Treosulfan pharmacokinetics
Children
Any condition that requires an allogeneic HSCT
Lead sponsor: Great Ormond Street Hospital for Children NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Newcastle-upon-Tyne Hospitals NHS Trust
First posted: 2014-01-29
Enrollment: 61
Sex: ALL
Minimum age (years): 28
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Children affected by malignant or non-malignant diseases with an indication to allogeneic HSCT.

Brief summary: 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).


Eligibility criteria: Inclusion Criteria:

1. age ≥ 28 days and ≤ 18 years old;
2. Karnofsky Performance Status ≥ 50 or Lansky Performance Status ≥ 30;
3. provide signed, written informed consent from parent or guardian;
4. be able to comply with study procedures and follow-up examinations;
5. have adequate organ function (as indicated by Table 1, page 27), within 14 days prior enrollment;
6. negative pregnancy test in post-pubertal female patients.

Exclusion Criteria:

1. patients aged \< 28 days and \> 18 years old;
2. patients with compromised organ function\*;
3. patients with any other severe concurrent disease, which, in the judgment of the Investigator, would make the patient inappropriate for entry into this study;
4. known hypersensitivity to Treosulfan or Fludarabine;
5. pregnancy/lactation.

Primary outcomes:
measure: 1) Assess maximum concentration (Cmax) after Treosulfan infusion in children prior to allogeneic haematopoietic stem cell transplantation.
timeFrame: day -7 and day -5 pre HSCT
measure: 2) Assess half life after Treosulfan infusion in children prior to allogeneic haematopoietic stem cell transplantation.
timeFrame: Day -7 and day-5 pre HSCT
measure: 3) Assess the area under the curve (AUC) after Treosulfan infusion in children prior to allogeneic haematopoietic stem cell transplantation.
timeFrame: Day -7 and day -5 pre HSCT
Secondary outcomes:
measure: 1) Assess interindividual and intraindividual variability of PK parameters in children of different age and weight;
timeFrame: day -7 and -5 pre HSCT
measure: 2) Assess the relationship between PK parameters and patient characteristics;
timeFrame: day -7 and -5 pre HSCT
measure: 3) Assess the relationship between Treosulfan PK and regimen related toxicity (using the NCI toxicity criteria scoring system) and survival;
timeFrame: from day -7 pre HSCT to day +100 post HSCT
measure: 4) Assess the relationship between Treosulfan PK and efficacy parameters, such as rate of engraftment and donor chimerism.
timeFrame: from day -7 pre HSCT to day + 360 post HSCT
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children
city: Newcastle Upon Tyne
country: United Kingdom
facility: Great North Childrens Hospital
Study officials:
affiliation: Great Ormond Street Hospital, London, UK
name: Robert Chiesa, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Great North Childrens Hospital, Newcastle upon Tyne, UK
name: Mary Slatter, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Slatter MA, Rao K, Amrolia P, Flood T, Abinun M, Hambleton S, Nademi Z, Goulden N, Davies G, Qasim W, Gaspar HB, Cant A, Gennery AR, Veys P. Treosulfan-based conditioning regimens for hematopoietic stem cell transplantation in children with primary immunodeficiency: United Kingdom experience. Blood. 2011 Apr 21;117(16):4367-75. doi: 10.1182/blood-2010-10-312082. Epub 2011 Feb 16.