Clinical trial NCT03664427: Pharmacogenetics of VOD in Children With HSCT
Official title: Pharmacogenetics of Veno-Occlusive Disease (VOD) in Children With Haematological Stem Cell Transplantation (HSCT)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cancer
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2018-09-10
Enrollment: 436
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: This study concerns children with cancer aged less than 18 years treated for their first HSCT between 2000 and 2011 in France.

Brief summary: This project aims to identify common pharmacogenetic biomarkers predisposing children with cancer to develop hepatic VOD during their cancer treatment including HSCT. The impact of VOD occurrence and significant biomarkers will also be evaluated on outcome at day 100 and one year after HSCT. It should help to highlight factors that can contribute to the initiation of hepatic VOD.

Understanding mechanisms of this toxicity and to know individual parameters of disease susceptibility becomes an important issue in the care of these children. The ultimate goal of research in this area would be to develop a personalized predictive medicine and, hopefully, prevent the occurrence of VOD from a therapeutic adaptation to each patient according to his pharmacogenetic profile (adapted prophylaxis, dose adjustment, drug combinations ...). A prospective identification of patients at risk of hepatic VOD will increase the safe use of anticancer.

Detailed description: Hematopoietic stem cells transplantation (HSCT) in children with cancer is source of veno-occlusive disease (VOD). This complication is unpredictable and serious by involving the vital prognosis of the child. In addition, this complication may affect the patient's quality of life and have serious long-term sequelae. The incidence varies from 15 to 60% and the mortality is greater than 60% after severe VOD. The risk factors of occurrence of these complications are, to date, unknown except for a susceptibility to some therapeutic (busulfan, radiotherapy ...). Pharmacogenetic aspects of hepatic VOD susceptibility are supposed and targeted screening supported this hypothesis. But pharmacogenetic predisposition to VOD was never explored with as many polymorphisms and considering the whole exome.

Eligibility criteria: Inclusion Criteria:

* Children with cancer aged less than 18 years old treated for their first HSCT between 2000 and 2011 in France.
* Patients are selected from the database ProMise regarding pediatric patients treated in any center of the French Society of Stem Cell transplantation (SFGM).
* Clinical data (age, sex, initial pathology, conditioning treatment, type of graft cells, VOD occurence or not, survival status at 100 days and 1 year after transplantation) were extracted from this database.

Exclusion Criteria:

-

Primary outcomes:
measure: Pharmacogenetic biomarkers
timeFrame: 12 months
Secondary outcomes:
measure: Survival status at 100 days post HSCT
timeFrame: 100 days
measure: Survival status at 1 year post HSCT
timeFrame: 12 months
Other outcomes:
Locations:
city: Paris
country: France
facility: Robert Debre Hospital
Study officials:
affiliation: APHP
name: Evelyne Jacqz-Aigrain, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: