Pediatric Hematopoietic Stem Cell TransplantationNCT06861257
Treosulfan Therapeutic Drug Monitoring in Pediatric Hematopoietic Stem Cell Transplant Recipients
An observational study of Pediatric Hematopoietic Stem Cell Transplantation and Malignant Disorders, run by Fondazione IRCCS Policlinico San Matteo di Pavia at 10 sites in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 18 years
- Conditions the study is for
- Pediatric Hematopoietic Stem Cell Transplantation, Malignant Disorders, Non-malignant Disorders
- How many people
- 70 participants
- Where
- 10 sitesItaly
- Study dates
- 24 Feb 2021to 31 Jul 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
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
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
10 sites in 1 country. Contact the study team or a site near you to ask about taking part.
10 sites in 1 country
Italy10 sites, 10 recruiting
- Recruiting
Policlinico Sant'Orsola Malpighi, Clinica Pediatrica Oncologia Ed Ematologia Pediatrica "Lalla Seràgnoli"
Bologna, bOLOGNA, 40138
Arcangelo Prete, +39051346044
- Recruiting
Ospedali Civili, Presidio Ospedale Dei Bambini, Oncoematologia Pediatrica e TMO
Brescia, Brescia, 25123
Fulvio Porta
- Recruiting
IRCCS Istituto Giannina Gaslini, U.O.S.D. Centro Trapianto di Midollo Osseo
Genova, Genova, 16147
Maura Faraci, +3901056362405
- Recruiting
Ospedale San Raffaele, U.O. Immunoematologia Pediatrica
Milan, Milano, 20132
Maria Ester Bernardo, +390226434875
- Recruiting
Fondazione IRCCS San Gerardo dei Tintori - Clinica Pediatrica
Monza, Monza-brianza, 20900
Sonia Bonanomi, +392332442
- Recruiting
Azienda Ospedaliera di Padova, Oncoematologia Pediatrica
Padova, Padova, 35128
Elisabetta Calore, +390498218030
- Recruiting
Fondazione IRCCS Policlinico San Matteo, S.C. Ematologia 2 - Oncoematologia Pediatrica
Pavia, Pavia, 27100
Marco Zecca, m.zecca@smatteo.pv.it
- Recruiting
AOU Città della Salute e della Scienza Di Torino, SC Oncoematologia Pediatrica e Centro Trapianti
Torino, Torino, 10126
Franca Fagioli, +390113135230
- Recruiting
IRCCS Materno Infantile "Burlo Garofolo", SC Oncoematologia Pediatrica e SS Trapianto Di Midollo
Trieste, Trieste, 34137
Natalia Maximova, +390403785565
- Recruiting
Ospedale Donna Bambino Azienda Ospedaliera Universitaria Integrata, U.O.C. Oncoematologia Pediatrica
Verona, VR, 37126
Simone cesaro, +390458127874
About this study
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.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
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%).
Measured: 100 days post HSCT
To evaluate the inter-individual and intra-individual variability of PK profile
a PK profile will be performed by collecting plasma samples for treo plasma concentration AUC measure
Measured: day 0-3
To study the cumulative incidence of non-relapse mortality at 100 days post HSCT
Measured: 100 days post HSCT
correlation between TREO exposure (measured by AUC) and efficacy
measured as time to engraftment and donor chimerism percentage post-HSCT
Measured: 1 year post HSCT
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2025
- Study start24 Feb 2021
- Primary completion31 Jul 2027 (estimated)
- Study completion31 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pediatric Hematopoietic Stem Cell TransplantationStudies of the same condition, open and under way.
- More trials run by Fondazione IRCCS Policlinico San Matteo di PaviaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fondazione IRCCS Policlinico San Matteo di Pavia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Marco Zecca, Fondazione IRCCS Policlinico San Matteo di Pavia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06861257
- Sponsor's protocol ID
- TREO
- Status last verified
- Apr 2026
- First submitted
- 24 Feb 2025
- Last updated
- 24 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treosulfan Therapeutic Drug Monitoring in Pediatric Hematopoietic Stem Cell Transplant Recipients
- ClinicalTrials.gov ID
- NCT06861257
- Acronym / sponsor ID
- TREO
- Conditions
- Pediatric Hematopoietic Stem Cell Transplantation, Malignant Disorders, Non-malignant Disorders
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- Fondazione IRCCS Policlinico San Matteo di PaviaUniversity, hospital or other
- Study start
- 24 Feb 2021 (actual)
- Primary completion
- 31 Jul 2027 (estimated)
- Study completion
- 31 Jul 2027 (estimated)
- First posted
- 6 Mar 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- Up to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- 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
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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
4 secondary outcomes
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
To evaluate the inter-individual and intra-individual variability of PK profile
Time frame: day 0-3
To study the cumulative incidence of non-relapse mortality at 100 days post HSCT
Time frame: 100 days post HSCT
correlation between TREO exposure (measured by AUC) and efficacy
Time frame: 1 year post HSCT
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Pediatric Hematopoietic Stem Cell Transplantation and Malignant Disorders, run by Fondazione IRCCS Policlinico San Matteo di Pavia at 10 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 24 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Marco Zecca, MD (+390382502848, m.zecca@smatteo.pv.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2026.