Treosulfan Therapeutic Drug Monitoring in Pediatric Hematopoietic Stem Cell Transplant Recipients

April 23, 2026 updated by: Marco Zecca, Fondazione IRCCS Policlinico San Matteo di Pavia
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
70

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Italy
    • Brescia
      • Brescia, Brescia, Italy, 25123
        • Recruiting
        • Ospedali Civili, Presidio Ospedale Dei Bambini, Oncoematologia Pediatrica e TMO
        • Contact:
          • Fulvio Porta
    • Genova
      • Genova, Genova, Italy, 16147
        • Recruiting
        • IRCCS Istituto Giannina Gaslini, U.O.S.D. Centro Trapianto di Midollo Osseo
        • Contact:
          • Maura Faraci
          • Phone Number: +3901056362405
    • Milano
      • Milan, Milano, Italy, 20132
        • Recruiting
        • Ospedale San Raffaele, U.O. Immunoematologia Pediatrica
        • Contact:
          • Maria Ester Bernardo
          • Phone Number: +390226434875
    • Monza-brianza
      • Monza, Monza-brianza, Italy, 20900
        • Recruiting
        • Fondazione IRCCS San Gerardo dei Tintori - Clinica Pediatrica
        • Contact:
          • Sonia Bonanomi
          • Phone Number: +392332442
    • Padova
      • Padova, Padova, Italy, 35128
        • Recruiting
        • Azienda Ospedaliera di Padova, Oncoematologia Pediatrica
        • Contact:
          • Elisabetta Calore
          • Phone Number: +390498218030
    • Pavia
      • Pavia, Pavia, Italy, 27100
        • Recruiting
        • Fondazione IRCCS Policlinico San Matteo, S.C. Ematologia 2 - Oncoematologia Pediatrica
        • Contact:
    • Torino
      • Torino, Torino, Italy, 10126
        • Recruiting
        • AOU Città della Salute e della Scienza Di Torino, SC Oncoematologia Pediatrica e Centro Trapianti
        • Contact:
          • Franca Fagioli
          • Phone Number: +390113135230
    • Trieste
      • Trieste, Trieste, Italy, 34137
        • Recruiting
        • IRCCS Materno Infantile "Burlo Garofolo", SC Oncoematologia Pediatrica e SS Trapianto Di Midollo
        • Contact:
          • Natalia Maximova
          • Phone Number: +390403785565
    • VR
      • Verona, VR, Italy, 37126
        • Recruiting
        • Ospedale Donna Bambino Azienda Ospedaliera Universitaria Integrata, U.O.C. Oncoematologia Pediatrica
        • Contact:
          • Simone cesaro
          • Phone Number: +390458127874
    • bOLOGNA
      • Bologna, bOLOGNA, Italy, 40138
        • Recruiting
        • Policlinico Sant'Orsola Malpighi, Clinica Pediatrica Oncologia Ed Ematologia Pediatrica "Lalla Seràgnoli"
        • Contact:
          • Arcangelo Prete
          • Phone Number: +39051346044

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

70 pediatric patients (aged 0 to 18 years) affected by malignant or non-malignant disorders and with an indication for HSCT will be enrolled at 13 transplantation sites

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Pediatric patients with a indication for HSCT and who will will receive TREO
Pediatric patients (aged 0 to 18 years) affected by malignant or non-malignant disorders and with an indication for HSCT and who will will receive TREO as part of the pre-transplant conditioning regimen, in combination with other chemotherapy agents.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
within 24 hours from the first dose

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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%).
100 days post HSCT
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
day 0-3
To study the cumulative incidence of non-relapse mortality at 100 days post HSCT
Time Frame: 100 days post HSCT
100 days post HSCT
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
1 year post HSCT

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Fondazione IRCCS Policlinico San Matteo di Pavia

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 24, 2021

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 31, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 31, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 24, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 28, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 6, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 24, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 23, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2026

More Information

Terms related to this study

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • TREO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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.

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