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NCT Number: NCT06861257

Treosulfan Therapeutic Drug Monitoring in Pediatric Hematopoietic Stem Cell Transplant Recipients

One of the major challenges to improve the outcome of hematopoietic stem cell transplantation (HSCT) is the reduction of toxicity and non-relapse mortality caused by the pre-transplant conditioning regimen, while maintaining efficacy. Treosulfan (TREO) (L-treitol-1,4-bis-methanesulfonate) is a busulfan analogue with a distinct site of alkylation that results in a more favourable toxicity profile in comparison with busulfan and total body irradiation. TREO is the prodrug of L-epoxybutane, a water-soluble bifunctional alkylating agent with remarkable myeloablative and immunosuppressive properties. The use of TREO, in combination with other chemotherapy agents, as part of the conditioning regimen for hematopoietic stem cell transplantation (HSCT) in children has progressively increased during the last decade for both malignant and non-malignant disorders. Data on TREO pharmacokinetics in the pediatric population are still scarce. To date, only a few studies, including small numbers of pediatric patients, have investigated the PK profile of TREO. These studies reported high variability of TREO pharmacokinetics, and the relationship between TREO exposure, toxicity and clinical outcome is still unresolved. Therefore, therapeutic drug monitoring with a personalized approach may be an important tool to optimize outcomes in the pediatric population. The aim of the investigators' study is to characterize TREO PK/PD profiles in children undergoing HSCT and to evaluate the relationship between TREO exposure and early toxicity and clinical outcome.

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Key information

Conditions

Pediatric Hematopoietic Stem Cell Transplantation Malignant Disorders Non-malignant Disorders

Age range

Up to 18 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Ospedali Civili, Presidio Ospedale Dei Bambini, Oncoematologia Pediatrica e TMO, Brescia, Italy

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • Age range 0 - 18 years.
  • Life expectancy > 12 weeks.
  • Diagnosis of malignant or non-malignant disorder.
  • Pre-HSCT Lansky / Karnofsky score ≥ 40%.
  • Indication to allogeneic or autologous HSCT with TREO as part of the pre-transplant conditioning regimen.
  • Negativity of pregnancy test for female patients.
  • Written informed consent signed by the parents or guardians.

Exclusion criteria

  • Absence of written informed consent signed by the parents or guardians.
  • Current clinically active infectious disease (including positive HIV serology or viral RNA).
  • Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure or left ventricular ejection fraction <40%).
  • Liver dysfunction (AST/ALT ≥ 3 times institutional upper limit normal value -ULN- or bilirubin > 3 times ULN).
  • Renal dysfunction: serum creatinine > 1.5 times ULN or calculated creatinine clearance < 60 ml/min/1.73 m2
  • End stage irreversible multi-system organ failure.
  • Pregnant or breast feeding female patient.

Treatment and study plan

Primary outcomes

  1. percentage of patients in therapeutic range after the first dose of TREO during the pre-transplant conditioning regimen

    Time frame: within 24 hours from the first dose

    proposed cumulative therapeutic target AUC 4800 mg x h /L; range 3840 -6000 mg x h /L

Secondary outcomes

  1. correlation between TREO exposure and early toxicity using the NCI Common Toxicity Criteria (Toxicity score 1- 5 for each organ/system) at 100 days post HSCT

    Time frame: 100 days post HSCT

    treo exposure is calculated by plasma concentration AUC measurement; correlation of out-of-range AUC(0-∞) and NCI grade will be analysed using the chi-square test. Intra and inter-individual variability will be estimated with a coefficient of variation (CV%).

  2. To evaluate the inter-individual and intra-individual variability of PK profile

    Time frame: day 0-3

    a PK profile will be performed by collecting plasma samples for treo plasma concentration AUC measure

  3. To study the cumulative incidence of non-relapse mortality at 100 days post HSCT

    Time frame: 100 days post HSCT

  4. correlation between TREO exposure (measured by AUC) and efficacy

    Time frame: 1 year post HSCT

    measured as time to engraftment and donor chimerism percentage post-HSCT

Study contacts

Contact information is provided by the study sponsor or research team.

Marco Zecca, MD

CONTACT

[email protected]

+390382502848

Sponsors and collaborators

Lead sponsor

Fondazione IRCCS Policlinico San Matteo di Pavia

Other

Registry information

Important dates

Study start
2021
Primary completion
2027
Study completion
2027
First posted
Mar 6, 2025
Registry last updated
Apr 24, 2026

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

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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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