Treosulfan Pharmacokinetics in Children Undergoing Allogeneic HSCT

NCT02048800 | Completed

• 1 other identifier: 10MI28
• Study Type: observational
• Target: 61
• Locations: 1 country
• Sites: 2

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).

Conditions

Allogeneic Haematopoietic Stem Cell Transplantation

Keywords

Treosulfan pharmacokinetics; Children; Any condition that requires an allogeneic HSCT

Outcome Measures

Primary Outcomes (3)

• 1) Assess maximum concentration (Cmax) after Treosulfan infusion in children prior to allogeneic haematopoietic stem cell transplantation.

  day -7 and day -5 pre HSCT

• 2) Assess half life after Treosulfan infusion in children prior to allogeneic haematopoietic stem cell transplantation.

  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.

  Day -7 and day -5 pre HSCT

Secondary Outcomes (4)

• 1) Assess interindividual and intraindividual variability of PK parameters in children of different age and weight;

  day -7 and -5 pre HSCT

• 2) Assess the relationship between PK parameters and patient characteristics;

  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;

  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.

  from day -7 pre HSCT to day + 360 post HSCT

Study Arms (1)

Treosulfan PK

Children with indication to HSCT receiving Treosulfan

Drug: Treosulfan

Interventions

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)

Treosulfan PK

Eligibility Criteria

• Age: 28 Days - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Children affected by malignant or non-malignant diseases with an indication to allogeneic HSCT.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Great Ormond Street Hospital for Children NHS Foundation Trust: lead
• Newcastle-upon-Tyne Hospitals NHS Trust: collaborator

Study Sites (2)

Great Ormond Street Hospital for Children

London, WC1N 3JH, United Kingdom

Location

Great North Childrens Hospital

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 21325599 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma will be stored for Treosulfan PK analysis.

MeSH Terms

Interventions

treosulfan

Study Officials

• Robert Chiesa, MD

  Great Ormond Street Hospital, London, UK

  PRINCIPAL INVESTIGATOR

• Mary Slatter, MD

  Great North Childrens Hospital, Newcastle upon Tyne, UK

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2014
• First Posted: January 29, 2014
• Study Start: March 1, 2014
• Primary Completion: July 31, 2017
• Study Completion: July 31, 2017
• Last Updated: September 4, 2019

Record last verified: 2019-09

Locations

GB (2)