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NCT Number: NCT02048800

Treosulfan Pharmacokinetics in Children Undergoing Allogeneic 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).

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Key information

Conditions

Allogeneic Haematopoietic Stem Cell Transplantation

Age range

28 day–18 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Great Ormond Street Hospital for Children, London, United Kingdom

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Treosulfan

Drug

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)

Primary outcomes

  1. 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

  2. 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

  3. 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

Secondary outcomes

  1. 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.

  2. 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).

  3. 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

  4. 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.

Sponsors and collaborators

Lead sponsor

Great Ormond Street Hospital for Children NHS Foundation Trust

Other

Collaborators

  • Newcastle-upon-Tyne Hospitals NHS Trust

Registry information

Official study title

Evaluation of Treosulfan Pharmacokinetics (PK) in Children Undergoing Allogeneic Haematopoietic Stem Cell Transplantation (HSCT)

Acronym: TreoPK

Important dates

Study start
2014
Primary completion
2017
Study completion
2017
First posted
Jan 29, 2014
Registry last updated
Sep 4, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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