Iron OverloadNCT04423237

Risk Factors and Measures to Prevent Liver and Pancreas Complications in Pediatric Patients After HSCT

An observational study of Iron Overload, run by University of Pisa at 1 site in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages Up to 17 years
Conditions the study is for: Iron Overload
What is being tested?: Deferasirox
How many people: 39 participants
Where: 1 siteItaly
Study dates: 30 Sep 2020to 31 Dec 2024
Phase: Observational
Are there results?: None posted in the registry

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 17 years
All sexes
No healthy volunteers
Child

Study population: Pediatric inpatients who a) underwent a HSCT at the Bone Marrow Transplant Center, IRCCS Burlo Garofalo, and b) had a ≥2-year follow-up after transplant. All procedures were performed according to clinical routine protocols

Who may be able to join

one or more allogeneic HSCT
any type of disease (blood-oncological or genetic), from any type of donor (sibling, MUD, haploidentical) and with any source of stem cells (spinal cord, peripheral blood stem cells, cord blood)
diagnosis of moderate-to-severe siderosis (by nuclear magnetic resonance imaging, MRI) and who needed a chelation treatment with deferasirox
one or more liver biopsies in the post-transplant period to perform histological examinations
Complete results from lab analyses
2-year follow-up after HSCT
therapeutic drug monitoring (TDM) protocol for deferasirox plasma concentration as per clinical routine
Sign of the informed consent by the parents or legal representatives

Who cannot join

Lack of liver biopsies after transplantation, results from laboratory analyses or TDM or MRI
Lack of informed consent

Trial locations and contacts

1 site in 1 country.

Italy1 site

IRCCS Burlo Garofolo
Trieste, 34137

Other trials in Italy

About this study

Official title: Identification of Risk Factors and Measures to Prevent Liver and Pancreas Complications in Pediatric Patients Undergoing a Hematopoietic Stem Cell Transplant (HSCT)

Hematopoietic Stem Cell Transplantation (HSCT) is currently a standard procedure for a wide range of blood-oncological diseases and genetic disorders. Recent improvements in transplant technologies, infection prevention and graft-versus-host-disease (GVHD) management procedures have significantly reduced the transplant-related mortality (TRM). However, approximately 50% of pediatric patients may develop liver dysfunction before HSCT and 74% to 85.5% after HSCT, with a TRM related to liver dysfunction reaching 46%. The liver and pancreas complications still remain too high for the difficulties and diagnostic inefficiencies and, consequently, for the lack of targeted and safer therapies. The diagnostic problems can be summarized in 3 major points: a) the histological examination of liver and pancreas parenchyma cannot be routinely performed because of the organ anatomy and the relative risk of the bioptic procedures; b) the lack of specific biomarkers or advanced imaging techniques appropriate for the diagnosis of HSCT complications; c) the multifactorial causes of organ complications, as well as drug toxicities, GVHD, siderosis, ductopenia (considered as an index of hepatic GVHD), the accumulation of potentially toxic substances favored by siderosis and ductopenia. In more than 50% of HSCT patients, siderosis and/or ductopenia may represent common pathological conditions. Furthermore, international guidelines issued by onco-hematology and transplantation scientific societies recommend a chelating treatment with deferasirox in all hematological and oncological patients undergoing an intense transfusion regimen. However, in the presence of siderosis and marked ductopenia, patients receiving deferasirox may experience both severe renal and hematological toxicities and lack of effectiveness of the chelating treatment.

Therefore, the principal aim of the present retrospective study will be the evaluation of the transplant-related mortality (TRM) in patients requiring a chelation treatment according to the Italian guidelines in pediatric patients

Read the detailed description

The present retrospective study will be conducted at the Bone Marrow Transplant Center, IRCCS Burlo Garofolo, Trieste, Italy. All pediatric patients who underwent one or more allogeneic HSCTs between 2010 and 2018 will be enrolled according to inclusion/exclusion criteria.

The following data will be collected in a retrospective manner:

Data on the underlying disease (diagnosis, therapeutic protocol, transfusion regimen, possible relapses, type of transplant, conditioning regimen, infectious complications, immunosuppressive treatment, including use of steroids);
Pre-transplant liver and pancreatic function, as well as quantification of iron content by nuclear magnetic resonance (MRI);
Pre-transplant histological evaluation of liver parenchyma in case of pre-existing liver disease;
Post-transplant liver and pancreatic function and the evaluation of parenchymal accumulation of Fe+;
Length and doses of DFX treatment, and corresponding drug plasma concentrations as per routine drug monitoring protocols;
Treatment tolerability according to CTC-AE grading V5.0, November 27, 2017 The post-transplant data will be collected within 2 years from HSCT (or the last HSCT when more than one).

The data entered in an appropriate anonymous database will be processed by descriptive statistics and uni- multivariate statistical analyses according to study endpoints. DFX plasma concentrations will be analyzed by means of to a nonlinear mixed effect modeling approach to elaborate a population pharmacokinetic (POP/PK) model. POP/PK findings will be further analyzed together with clinical and laboratory data.

Conditions: Iron Overload
Being tested: Deferasirox
Keywords: iron overload, deferasirox, children, HSCT, toxicity, ductopenia
Medical subject headings: Iron Overload

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

DeferasiroxDrug
Also called Exjade or Deferasirox Milan
DEFERASIROX administered as per clinical practice and according to technical note

Study groups in NCT04423237
Study group	Role	What they receive
Severe Iron Overload (SIO)		Children affected by Severe Iron Overload who received DEFERASIROX Receives: Drug: Deferasirox
Severe Iron Overload + Ductopenia (SIO+D)		Children affected by Severe Iron Overload + Ductopenia who received DEFERASIROX Receives: Drug: Deferasirox

What is being measured

The primary outcome is the main question the study is designed to answer.

Transplant-related mortality (TRM)
TRM in SIO/SIO+D patients treated with deferasirox as per Italian guidelines
Measured: 0-24 months after transplant

Secondary outcomes (5)

Post-HSCT liver and pancreatic complications
Incidence of post-HSCT liver and pancreatic complications in SIO/SIO+D patients treated with deferasirox as per Italian guidelines
Measured: 0-24 months after transplant
Time to iron concentration normalization
The times required for the normalization of the Iron Concentration in SIO and SIO+D patients
Measured: 0-24 months after transplant
Statistical analysis of risk factors for ductopenia
The correlation between ductopenia and potential risk factors will be investigated by uni- and multi-variate analyses. The following data will be included in the analyses as potential risk factors: chemo-radiotherapy regimens prior to HSCT (drugs and doses), number of blood transfusions
Measured: 0-24 months after transplant
Minimum plasma concentrations of deferasirox
In SIO/SIO+D patients, a factorial analysis for mixed data and a nonlinear mixed effect modeling approach will be used to investigate plasma pharmacokinetics of deferasirox in terms of patients' exposure (minimum plasma concentration, Cmin) and to evaluate the effect of identified covariates on drug disposition.
Measured: 0-24 months after transplant
Correlation of minimum plasma concentrations of deferasirox with drug tolerability
In SIO/SIO+D patients, uni- and multi-variate analyses will be adopted to assess the correlation of Cmin with treatment tolerability
Measured: 0-24 months after transplant

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

30 Sep 202031 Dec 2024

First posted9 Jun 2020
Study start30 Sep 2020
Primary completion30 Jun 2024
Study completion31 Dec 2024

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Iron OverloadStudies of the same condition, open and under way.
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: Case-control
Time perspective: Retrospective
Enrolment: 39 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04423237
Sponsor's protocol ID: 1105/2015
Status last verified: Jun 2025
First submitted: 30 May 2020
Last updated: 3 Jun 2025
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

Publications

Maximova N, Zanon D, Pascolo L, Zennaro F, Gregori M, Grosso D, Sonzogni A. Metal accumulation in the renal cortex of a pediatric patient with sickle cell disease: a case report and review of the literature. J Pediatr Hematol Oncol. 2015 May;37(4):311-4. doi: 10.1097/MPH.0000000000000322.
PubMed 25811747
Galeotti L, Ceccherini F, Fucile C, Marini V, Di Paolo A, Maximova N, Mattioli F. Evaluation of Pharmacokinetics and Pharmacodynamics of Deferasirox in Pediatric Patients. Pharmaceutics. 2021 Aug 11;13(8):1238. doi: 10.3390/pharmaceutics13081238.
PubMed 34452199

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Iron Overload trials

Study at a glance

From the registry record, last updated by the sponsor on 3 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Identification of Risk Factors and Measures to Prevent Liver and Pancreas Complications in Pediatric Patients Undergoing a Hematopoietic Stem Cell Transplant (HSCT)
ClinicalTrials.gov ID: NCT04423237
Acronym / sponsor ID: 1105/2015
Conditions: Iron Overload
Keywords: iron overload, deferasirox, children, HSCT, toxicity, ductopenia
Study type: Observational
Recruitment status: Completed
Enrolment: 39 participants (actual)
Lead sponsor: University of PisaUniversity, hospital or other
Collaborators: IRCCS Burlo Garofolo, University of Genova
Study start: 30 Sep 2020 (actual)
Primary completion: 30 Jun 2024 (actual)
Study completion: 31 Dec 2024 (actual)
First posted: 9 Jun 2020 (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.

Detailed description

The following data will be collected in a retrospective manner:

Data on the underlying disease (diagnosis, therapeutic protocol, transfusion regimen, possible relapses, type of transplant, conditioning regimen, infectious complications, immunosuppressive treatment, including use of steroids);
Pre-transplant liver and pancreatic function, as well as quantification of iron content by nuclear magnetic resonance (MRI);
Pre-transplant histological evaluation of liver parenchyma in case of pre-existing liver disease;
Post-transplant liver and pancreatic function and the evaluation of parenchymal accumulation of Fe+;
Length and doses of DFX treatment, and corresponding drug plasma concentrations as per routine drug monitoring protocols;
Treatment tolerability according to CTC-AE grading V5.0, November 27, 2017 The post-transplant data will be collected within 2 years from HSCT (or the last HSCT when more than one).

Study design

Observational model: Case-control
Time perspective: Retrospective
Number of arms: 2

Arm	Type	Receives
Severe Iron Overload (SIO)	–	Drug: DeferasiroxChildren affected by Severe Iron Overload who received DEFERASIROX
Severe Iron Overload + Ductopenia (SIO+D)	–	Drug: DeferasiroxChildren affected by Severe Iron Overload + Ductopenia who received DEFERASIROX

Who may qualify

Ages: Up to 17 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child
Study population: Pediatric inpatients who a) underwent a HSCT at the Bone Marrow Transplant Center, IRCCS Burlo Garofalo, and b) had a ≥2-year follow-up after transplant. All procedures were performed according to clinical routine protocols

Key inclusion criteria (8 listed)

one or more allogeneic HSCT
any type of disease (blood-oncological or genetic), from any type of donor (sibling, MUD, haploidentical) and with any source of stem cells (spinal cord, peripheral blood stem cells, cord blood)
diagnosis of moderate-to-severe siderosis (by nuclear magnetic resonance imaging, MRI) and who needed a chelation treatment with deferasirox
one or more liver biopsies in the post-transplant period to perform histological examinations
Complete results from lab analyses

Key exclusion criteria (2 listed)

Lack of liver biopsies after transplantation, results from laboratory analyses or TDM or MRI
Lack of informed consent

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
DeferasiroxAlso: Exjade or Deferasirox MilanDEFERASIROX administered as per clinical practice and according to technical note	Drug	Severe Iron Overload (SIO), Severe Iron Overload + Ductopenia (SIO+D)

Primary outcome

Transplant-related mortality (TRM)
Time frame: 0-24 months after transplant
TRM in SIO/SIO+D patients treated with deferasirox as per Italian guidelines

5 secondary outcomes

Post-HSCT liver and pancreatic complications
Time frame: 0-24 months after transplant
Time to iron concentration normalization
Time frame: 0-24 months after transplant
Statistical analysis of risk factors for ductopenia
Time frame: 0-24 months after transplant
Minimum plasma concentrations of deferasirox
Time frame: 0-24 months after transplant
Correlation of minimum plasma concentrations of deferasirox with drug tolerability
Time frame: 0-24 months after transplant

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2025.
Background: PubMed 25811747Maximova N, Zanon D, Pascolo L, Zennaro F, Gregori M, Grosso D, Sonzogni A. Metal accumulation in the renal cortex of a pediatric patient with sickle cell disease: a case report and review of the literature. J Pediatr Hematol Oncol. 2015 May;37(4):311-4. doi: 10.1097/MPH.0000000000000322.
Results publication: PubMed 34452199Galeotti L, Ceccherini F, Fucile C, Marini V, Di Paolo A, Maximova N, Mattioli F. Evaluation of Pharmacokinetics and Pharmacodynamics of Deferasirox in Pediatric Patients. Pharmaceutics. 2021 Aug 11;13(8):1238. doi: 10.3390/pharmaceutics13081238.

Related trials for Iron Overload

Active, not recruitingPhase 2
Treatment of Hemochromatosis
Hemochromatosis
Active, not recruitingObservational study
Ethnic Differences in Iron Absorption (FeGenes)
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Active, not recruitingObservational study
Heme and Non-heme Iron Intakes, Gut Microbiota, and Influence on Host Iron Absorption
Anemia, Iron Deficiency, Iron Overload
Active, not recruitingPhase 2
Efficacy and Safety of Vamifeport in Adult Participants With Homeostatic Iron Regulator Gene (HFE)-Related Hereditary Hemochromatosis
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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. This study is not recruiting at the moment.

Natalia Maximova, MD study director

Institute for Maternal and Child Health, IRCCS Burlo Garofalo, Trieste, Italy

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

An observational study of Iron Overload, run by University of Pisa at 1 site 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 8 inclusion and 2 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: finished, as of the sponsor's last update on 3 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Transplant-related mortality (TRM) (time frame: 0-24 months after transplant). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04423237, which also lists 2 linked publications.

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 3 Jun 2025.