New Biomarker-based Strategy to Screen and Monitor for Activated Phosphoinositide 3-kinase Δ Syndrome

NCT ID: NCT06694363

Last Updated: 2024-11-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Total Enrollment

14 participants

Study Classification

OBSERVATIONAL

Study Start Date

2024-12-31

Study Completion Date

2029-05-31

Brief Summary

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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

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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.

Conditions

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Activated PI3K Delta Syndrome

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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1 - initiating treatment

10 patients with a genetic diagnosis of APDS type 1 or type 2 who are to be treated with a selective PI3Kδ inhibitor, Lenolisib.

Blood samples

Intervention Type BIOLOGICAL

A maximum of 27 ml of blood collected at each visit for metabolic markers analysis

Urine samples

Intervention Type BIOLOGICAL

One urine sample collected at each visit for enteric virus infection research

Stool samples

Intervention Type BIOLOGICAL

One stool sample collected at each visit for enteric virus infection research

2 - already on treatment

4 patients with a genetic diagnosis of APDS type 1 or type 2 already treated with a selective PI3Kδ inhibitor, Lenolisib.

Blood samples

Intervention Type BIOLOGICAL

A maximum of 27 ml of blood collected at each visit for metabolic markers analysis

Urine samples

Intervention Type BIOLOGICAL

One urine sample collected at each visit for enteric virus infection research

Stool samples

Intervention Type BIOLOGICAL

One stool sample collected at each visit for enteric virus infection research

Interventions

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Blood samples

A maximum of 27 ml of blood collected at each visit for metabolic markers analysis

Intervention Type BIOLOGICAL

Urine samples

One urine sample collected at each visit for enteric virus infection research

Intervention Type BIOLOGICAL

Stool samples

One stool sample collected at each visit for enteric virus infection research

Intervention Type BIOLOGICAL

Eligibility Criteria

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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.
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sven Kracker, PHD

Role: STUDY_DIRECTOR

Institut National de la Santé Et de la Recherche Médicale, France

Locations

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Hôpital Haut Levêque - BORDEAUX

Bordeaux, , France

Site Status

Hôpital Pellerin Enfants - BORDEAUX

Bordeaux, , France

Site Status

Hôpital Jeanne de Flandres - LILLE

Lille, , France

Site Status

Hôpital La Timone adulte - MARSEILLE

Marseille, , France

Site Status

Hôpital Necker Enfants Malades - PARIS

Paris, , France

Site Status

CHU IUCT Oncopole - TOULOUSE

Toulouse, , France

Site Status

Hôpital des enfants - TOULOUSE

Toulouse, , France

Site Status

Countries

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France

Central Contacts

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Michaela SEMERARO, MD, PhD

Role: CONTACT

01 42 19 27 16 ext. +33

Laure CHOUPEAUX, MSc

Role: CONTACT

01 44 38 17 11 ext. +33

Facility Contacts

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Jean François VIALLARD, MD, PhD

Role: primary

Nathalie ALADJIDI, MD

Role: primary

Wadih ABOU-CHALA, MD

Role: primary

Nicolas SCHLEINITZ, MD, PhD

Role: primary

Michaela SEMERARO, MD, PhD

Role: primary

Pierre COUGOUL, MD

Role: primary

Marlène PASQUET, MD

Role: primary

Other Identifiers

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APHP240329

Identifier Type: -

Identifier Source: org_study_id

2024-A01816-41

Identifier Type: REGISTRY

Identifier Source: secondary_id

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