Clinical trial NCT06861257: Treosulfan Therapeutic Drug Monitoring in Pediatric Hematopoietic Stem Cell Transplant Recipients
Official title: Treosulfan Therapeutic Drug Monitoring in Pediatric Hematopoietic Stem Cell Transplant Recipients
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Pediatric Hematopoietic Stem Cell Transplantation
Malignant Disorders
Non-malignant Disorders
Lead sponsor: Fondazione IRCCS Policlinico San Matteo di Pavia
Sponsor class: OTHER
First posted: 2025-03-06
Enrollment: 70
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: percentage of patients in therapeutic range after the first dose of TREO during the pre-transplant conditioning regimen
timeFrame: within 24 hours from the first dose
Secondary outcomes:
measure: 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
timeFrame: 100 days post HSCT
measure: To evaluate the inter-individual and intra-individual variability of PK profile
timeFrame: day 0-3
measure: To study the cumulative incidence of non-relapse mortality at 100 days post HSCT
timeFrame: 100 days post HSCT
measure: correlation between TREO exposure (measured by AUC) and efficacy
timeFrame: 1 year post HSCT
Other outcomes:
Locations:
city: Monza
country: Italy
facility: Fondazione IRCCS San Gerardo dei Tintori - Clinica Pediatrica
state: Monza-brianza
city: Verona
country: Italy
facility: Ospedale Donna Bambino Azienda Ospedaliera Universitaria Integrata, U.O.C. Oncoematologia Pediatrica
state: VR
city: Bologna
country: Italy
facility: Policlinico Sant'Orsola Malpighi, Clinica Pediatrica Oncologia Ed Ematologia Pediatrica "Lalla Seràgnoli"
city: Brescia
country: Italy
facility: Ospedali Civili, Presidio Ospedale Dei Bambini, Oncoematologia Pediatrica e TMO
city: Genova
country: Italy
facility: IRCCS Istituto Giannina Gaslini, U.O.S.D. Centro Trapianto di Midollo Osseo
city: Milano
country: Italy
facility: Ospedale San Raffaele, U.O. Immunoematologia Pediatrica
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova, Oncoematologia Pediatrica
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo, S.C. Ematologia 2 - Oncoematologia Pediatrica
city: Torino
country: Italy
facility: AOU Città della Salute e della Scienza Di Torino, SC Oncoematologia Pediatrica e Centro Trapianti
city: Trieste
country: Italy
facility: IRCCS Materno Infantile "Burlo Garofolo", SC Oncoematologia Pediatrica e SS Trapianto Di Midollo
Study officials:
References: