Treosulfan Therapeutic Drug Monitoring in Pediatric Hematopoietic Stem Cell Transplant Recipients

NCT06861257 | Recruiting

• 1 other identifier: TREO
• Study Type: observational
• Target: 70
• Locations: 1 country
• Sites: 10

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.

Conditions

Malignant Disorders; Non-malignant Disorders; Pediatric Hematopoietic Stem Cell Transplantation

Outcome Measures

Primary Outcomes (1)

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

  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 Outcomes (4)

• 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

  100 days post HSCT

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

  day 0-3

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

  100 days post HSCT

• correlation between TREO exposure (measured by AUC) and efficacy

  1 year post HSCT

Study Arms (1)

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.

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• 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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fondazione IRCCS Policlinico San Matteo di Pavia: lead

Study Sites (10)

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

Bologna, bOLOGNA, 40138, Italy

RECRUITING

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

Brescia, Brescia, 25123, Italy

RECRUITING

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

Genova, Genova, 16147, Italy

RECRUITING

Ospedale San Raffaele, U.O. Immunoematologia Pediatrica

Milan, Milano, 20132, Italy

RECRUITING

Fondazione IRCCS San Gerardo dei Tintori - Clinica Pediatrica

Monza, Monza-brianza, 20900, Italy

RECRUITING

Azienda Ospedaliera di Padova, Oncoematologia Pediatrica

Padova, Padova, 35128, Italy

RECRUITING

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

Pavia, Pavia, 27100, Italy

RECRUITING

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

Torino, Torino, 10126, Italy

RECRUITING

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

Trieste, Trieste, 34137, Italy

RECRUITING

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

Verona, VR, 37126, Italy

RECRUITING

Central Study Contacts

Marco Zecca, MD

CONTACT

+390382502848; m.zecca@smatteo.pv.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Pediatric Oncohematology Department

Study Record Dates

• First Submitted: February 24, 2025
• First Posted: March 6, 2025
• Study Start: February 24, 2021
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): July 31, 2027
• Last Updated: April 24, 2026

Record last verified: 2026-04

Locations

IT (10)