Clinical trial NCT06694363: New Biomarker-based Strategy to Screen and Monitor for Activated Phosphoinositide 3-kinase Δ Syndrome
Official title: New Biomarker-based Strategy to Screen and Monitor for Activated Phosphoinositide 3-kinase Δ Syndrome
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Activated PI3K Delta Syndrome
Keywords: Activated PI3K delta syndromes
APDS
Leniolisib
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2024-11-19
Enrollment: 14
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with genetic diagnosis of APDS type 1 or type 2 and planned to be treated by PI3Kδ selective inhibitor leniolisib and patients with genetic diagnosis of APDS type 1 or type 2 already treated by PI3Kδ selective inhibitor leniolisib in the last 2 years

Brief summary: The study would like to compare patient samples at different time points using state-of the art-phenotyping tools.

Collection of blood samples of APDS patients undergoing PI3K inhibitor treatment will be collected when feasible according to the standard of care planning (a blood test is supposed to be performed for these patients at M0-M3-M6-M12 then each 6 months for a total period of 2 years from the beginning of the PI3K inhibitor treatment).

The whole blood will be processed in order to isolate the peripheral blood mononuclear cells (PBMC) and the plasma. Serum, RNA and DNA extraction will be performed on a separate sample.

Detailed description: Activated PI3K delta syndromes (PI3Kδ) (APDS type 1 and type 2) are combined immunodeficiencies with variable clinical manifestations caused by heterozygous gain-of-function mutations of the PIK3CD gene. APDS is a very young onset disease, most clinical manifestations appear in pediatric age. Patients may experience severe, disabling, and life-threatening clinical manifestations. Additionally, they may exhibit autoimmunity in addition to immune deficiency. APDS patients present a high risk of developing tumors especially B lymphomas. Hematopoietic stem cell transplantation (HSCT) is the only curative option and, given the risks, may be considered for patients with severe APDS (including those who have developed lymphoma). HSCT is curative, but carries a 10 to 20% mortality risk and cannot guarantee reversibility of organ damage. Positive data from the phase II/III study of the PI3Kδ selective inhibitor leniolisib met the co-primary criteria of reduced lymph node size and increased percentage of B naïve cells in patients with APDS. In addition, safety data from the study showed that leniolisib was well tolerated by participants. The drug is also under review by the European Medicines Agency and a marketing authorization for APDS patients older than 12 years old will be soon available. In the meantime the access to this drug is available by compassionate use for patients older than 12 years old.

In this context, it will be interesting to evaluate the clinical and biological profile of these patients before and after leniolisib treatment in order to identify useful biomarkers for the follow up of the disease. In addition, carful long-term monitoring of patients under PI3Kδ inhibitors is mandatory to detect adverse effects of iatrogenic overinhibition of the PI3K pathway.

Eligibility criteria: Inclusion Criteria:

Group 1:

* Patients with genetic diagnosis of APDS type 1 or type 2 and planned to be treated by PI3Kδ selective inhibitor leniolisib
* Primary immunodeficient patients with new disease-causing variants in the PIK3CD gene or PIK3R1 gene
* Minimum age 12 years old
* Patients or holders of parental authority do not oppose participation in this research.
* Patients affiliated to a Health Insurance scheme or beneficiaries

Group 2 :

* Patients with genetic diagnosis of APDS type 1 or type 2 already treated by PI3Kδ selective inhibitor leniolisib in the last 2 years
* Patients whose pre-treatment samples are available/analyzable
* Minimum age 12 years old
* Patients or holders of parental authority do not oppose participation in this research.
* patients affiliated to a Health Insurance scheme or beneficiaries

Exclusion Criteria:

* Bone marrow transplantation
* Refusal to participate to the study.

Primary outcomes:
measure: Biomarker
timeFrame: At 0 day, 3 months, 6 months, 12 months, 18 months and 24 months of treatment
Secondary outcomes:
measure: activation-induced cytidine deaminase (AID) off-target activity
timeFrame: At 0 day, 3 months, 6 months, 12 months, 18 months and 24 months of treatment
measure: Correlation between biological data with the clinical data
timeFrame: At 0 day, 3 months, 6 months, 12 months, 18 months and 24 months of treatment
measure: Enteric virus infection research
timeFrame: At 0 day, 3 months, 6 months, 12 months, 18 months and 24 months of treatment
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Hôpital Haut Levêque - BORDEAUX
city: Bordeaux
country: France
facility: Hôpital Pellerin Enfants - BORDEAUX
city: Lille
country: France
facility: Hôpital Jeanne de Flandres - LILLE
city: Marseille
country: France
facility: Hôpital La Timone adulte - MARSEILLE
city: Paris
country: France
facility: Hôpital Necker Enfants Malades - PARIS
city: Toulouse
country: France
facility: CHU IUCT Oncopole - TOULOUSE
city: Toulouse
country: France
facility: Hôpital des enfants - TOULOUSE
Study officials:
affiliation: Institut National de la Santé Et de la Recherche Médicale, France
name: Sven Kracker, PHD
role: STUDY_DIRECTOR
References: