Treosulfan Therapeutic Drug Monitoring in Pediatric Hematopoietic Stem Cell Transplant Recipients

NCT ID: NCT06861257

Last Updated: 2025-03-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

70 participants

Study Classification

OBSERVATIONAL

Study Start Date

2021-02-24

Study Completion Date

2025-12-31

Brief Summary

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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.

Detailed Description

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Conditions

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Pediatric Hematopoietic Stem Cell Transplantation Malignant Disorders Non-malignant Disorders

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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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.

No interventions assigned to this group

Eligibility Criteria

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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.
Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fondazione IRCCS Policlinico San Matteo di Pavia

OTHER

Sponsor Role lead

Responsible Party

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Marco Zecca

Head of Pediatric Oncohematology Department

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Policlinico Sant'Orsola Malpighi, Clinica Pediatrica Oncologia Ed Ematologia Pediatrica "Lalla Seràgnoli"

Bologna, bOLOGNA, Italy

Site Status RECRUITING

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

Brescia, Brescia, Italy

Site Status RECRUITING

IRCCS Istituto Giannina Gaslini, U.O.S.D. Centro Trapianto di Midollo Osseo

Genova, Genova, Italy

Site Status RECRUITING

Ospedale San Raffaele, U.O. Immunoematologia Pediatrica

Milan, Milano, Italy

Site Status RECRUITING

Fondazione IRCCS San Gerardo dei Tintori - Clinica Pediatrica

Monza, monza-brianza, Italy

Site Status RECRUITING

Azienda Ospedaliera di Padova, Oncoematologia Pediatrica

Padua, Padova, Italy

Site Status RECRUITING

Fondazione IRCCS Policlinico San Matteo, S.C. Ematologia 2 - Oncoematologia Pediatrica

Pavia, pavia, Italy

Site Status RECRUITING

AOU Città della Salute e della Scienza Di Torino, SC Oncoematologia Pediatrica e Centro Trapianti

Torino, torino, Italy

Site Status RECRUITING

IRCCS Materno Infantile "Burlo Garofolo", SC Oncoematologia Pediatrica e SS Trapianto Di Midollo

Trieste, Trieste, Italy

Site Status RECRUITING

Ospedale Donna Bambino Azienda Ospedaliera Universitaria Integrata, U.O.C. Oncoematologia Pediatrica

Verona, VR, Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Marco Zecca, MD

Role: CONTACT

+390382502848

Facility Contacts

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Arcangelo Prete

Role: primary

+39051346044

Fulvio Porta

Role: primary

Maura Faraci

Role: primary

+3901056362405

Maria Ester Bernardo

Role: primary

+390226434875

Sonia Bonanomi

Role: primary

+392332442

Elisabetta Calore

Role: primary

+390498218030

Marco Zecca

Role: primary

Franca Fagioli

Role: primary

+390113135230

Natalia Maximova

Role: primary

+390403785565

Simone cesaro

Role: primary

+390458127874

Other Identifiers

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TREO

Identifier Type: -

Identifier Source: org_study_id

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