Alpelisib in Pediatric and Adult Patients With Lymphatic Malformations Associated With a PIK3CA Mutation.

NCT ID: NCT05948943

Last Updated: 2025-11-12

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

RECRUITING

Clinical Phase

PHASE2/PHASE3

Total Enrollment

232 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-11-24

Study Completion Date

2033-05-02

Brief Summary

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The main purpose of this study in participants with PIK3CA-mutated LyM is to assess the change in radiological response and symptom severity upon treatment with alpelisib film-coated tablets (FCT) as compared to placebo.

Detailed Description

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This is a phase II/III multi-center study with two stages:

* Stage 1 is designed to select the dose(s) for the confirmatory phase (DSCP) for alpelisib in Stage 2 and will comprise a 24-week open-label core phase in adult (≥18 years of age) and pediatric participants (6-17 years of age) with PIK3CA-mutated LyM, followed by an extension. After eligibility has been confirmed at screening, participants will be randomized in a 1:1 ratio to the different alpelisib doses according to their age. Depending on the results at the end of Stage 1 core phase, the Stage 2 will be opened to adult and/or pediatric participants or the study may be stopped.
* Stage 2 is designed to confirm the efficacy and assess safety of alpelisib at the DSCP in participants with PIK3CA-mutated LyM and will comprise a 24-week randomized, double blind, placebo-controlled confirmatory phase in adult (≥18 years of age) and pediatric participants 6-17 years of age followed by an open-label extension. After eligibility has been confirmed at screening participants will be randomized in a 2:1 ratio to alpelisib or placebo.

Additionally, in parallel, Stage 2 will include a 24-week open-label core phase in pediatric participants 0-5 years of age followed by an extension, if pediatric participants will be enrolling in Stage 2.

Based on the results of the 24-week open-label core phase of Stage 1, the dose(s) for Stage 2 will be selected by Novartis in consultation with the Steering Committee (SC). During the 24-week randomized, double blind, placebo-controlled core phase of Stage 2, an Independent Data Monitoring Committee (DMC) will conduct periodic safety and efficacy reviews to assess the risk benefit profile of the treatment.

Conditions

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Lymphatic Malformations

Keywords

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Lymphatic malformations (LyM) Cystic lymphangioma Cystic hygroma Lymphangioma circumscriptum Cavernous lymphangioma Lymphangioma Macrocystic lymphatic malformation Microcystic lymphatic malformationn Alpelisib

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Pediatric participants (6-17 years of age), alpelisib dose 2 (Stage 1)

Pediatric participants 6-17 years of age who will receive dose 2 of alpelisib in an open-label fashion for at least 24 weeks unless they discontinue earlier (Stage 1)

Group Type EXPERIMENTAL

Alpelisib

Intervention Type DRUG

In Stage 1: adult participants (≥18 years of age) will receive dose 1 or dose 2 of alpelisib; pediatric participants (6-17 years of age) will receive dose 2 or dose 3 of alpelisib.

In Stage 2: Adult participants will receive alpelisib at the dose selected for confirmatory phase in adult participants; pediatric participants (6-17 years of age) will will receive alpelisib at the dose selected for confirmatory phase in pediatric participants; and pediatric participants of 0-5 years of age will receive dose 3 of alpelisib

Pediatric participants (6-17 years of age), alpelisib dose 3 (Stage 1)

Pediatric participants 6-17 years of age who will receive dose 3 of alpelisib in an open-label fashion for at least 24 weeks unless they discontinue earlier (Stage 1).

Group Type EXPERIMENTAL

Alpelisib

Intervention Type DRUG

In Stage 1: adult participants (≥18 years of age) will receive dose 1 or dose 2 of alpelisib; pediatric participants (6-17 years of age) will receive dose 2 or dose 3 of alpelisib.

In Stage 2: Adult participants will receive alpelisib at the dose selected for confirmatory phase in adult participants; pediatric participants (6-17 years of age) will will receive alpelisib at the dose selected for confirmatory phase in pediatric participants; and pediatric participants of 0-5 years of age will receive dose 3 of alpelisib

Adult participants, alpelisib (Stage 2)

Adult participants (≥18 years of age) who will receive alpelisib at the dose selected for confirmatory phase in adult participants (Stage 2)

Group Type EXPERIMENTAL

Alpelisib

Intervention Type DRUG

In Stage 1: adult participants (≥18 years of age) will receive dose 1 or dose 2 of alpelisib; pediatric participants (6-17 years of age) will receive dose 2 or dose 3 of alpelisib.

In Stage 2: Adult participants will receive alpelisib at the dose selected for confirmatory phase in adult participants; pediatric participants (6-17 years of age) will will receive alpelisib at the dose selected for confirmatory phase in pediatric participants; and pediatric participants of 0-5 years of age will receive dose 3 of alpelisib

Adult participants, placebo (Stage 2)

Adult participants (≥18 years of age) who will receive matching placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

In Stage 2, participants will receive matching placebo for 24 weeks of the study

Pediatric participants (6-17 years of age), alpelisib (Stage 2)

Pediatric participants (6-17 years of age) who will receive alpelisib at the dose selected for confirmatory phase in pediatric participants (Stage 2)

Group Type EXPERIMENTAL

Alpelisib

Intervention Type DRUG

In Stage 1: adult participants (≥18 years of age) will receive dose 1 or dose 2 of alpelisib; pediatric participants (6-17 years of age) will receive dose 2 or dose 3 of alpelisib.

In Stage 2: Adult participants will receive alpelisib at the dose selected for confirmatory phase in adult participants; pediatric participants (6-17 years of age) will will receive alpelisib at the dose selected for confirmatory phase in pediatric participants; and pediatric participants of 0-5 years of age will receive dose 3 of alpelisib

Pediatric participants (6-17 years of age), placebo (Stage 2)

Pediatric participants (6-17 years of age) who will receive matching placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

In Stage 2, participants will receive matching placebo for 24 weeks of the study

Pediatric participants (0-5 years of age), alpelisib (Stage 2)

Pediatric participants of 0-5 years who will dose 3 of alpelisib in an open-label fashion for at least 24 weeks unless they discontinue earlier

Group Type EXPERIMENTAL

Alpelisib

Intervention Type DRUG

In Stage 1: adult participants (≥18 years of age) will receive dose 1 or dose 2 of alpelisib; pediatric participants (6-17 years of age) will receive dose 2 or dose 3 of alpelisib.

In Stage 2: Adult participants will receive alpelisib at the dose selected for confirmatory phase in adult participants; pediatric participants (6-17 years of age) will will receive alpelisib at the dose selected for confirmatory phase in pediatric participants; and pediatric participants of 0-5 years of age will receive dose 3 of alpelisib

Adult participants, alpelisib dose 1 (Stage 1)

Adult participants (≥18 years of age) who will receive dose 1 of alpelisib an open-label fashion for at least 24 weeks unless they discontinue earlier (Stage 1)

Group Type EXPERIMENTAL

Alpelisib

Intervention Type DRUG

In Stage 1: adult participants (≥18 years of age) will receive dose 1 or dose 2 of alpelisib; pediatric participants (6-17 years of age) will receive dose 2 or dose 3 of alpelisib.

In Stage 2: Adult participants will receive alpelisib at the dose selected for confirmatory phase in adult participants; pediatric participants (6-17 years of age) will will receive alpelisib at the dose selected for confirmatory phase in pediatric participants; and pediatric participants of 0-5 years of age will receive dose 3 of alpelisib

Adult participants, alpelisib dose 2 (Stage 1)

Adult participants (≥18 years of age) who will receive dose 2 of alpelisib in an open-label fashion for at least 24 weeks unless they discontinue earlier (Stage 1).

Group Type EXPERIMENTAL

Alpelisib

Intervention Type DRUG

In Stage 1: adult participants (≥18 years of age) will receive dose 1 or dose 2 of alpelisib; pediatric participants (6-17 years of age) will receive dose 2 or dose 3 of alpelisib.

In Stage 2: Adult participants will receive alpelisib at the dose selected for confirmatory phase in adult participants; pediatric participants (6-17 years of age) will will receive alpelisib at the dose selected for confirmatory phase in pediatric participants; and pediatric participants of 0-5 years of age will receive dose 3 of alpelisib

Interventions

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Alpelisib

In Stage 1: adult participants (≥18 years of age) will receive dose 1 or dose 2 of alpelisib; pediatric participants (6-17 years of age) will receive dose 2 or dose 3 of alpelisib.

In Stage 2: Adult participants will receive alpelisib at the dose selected for confirmatory phase in adult participants; pediatric participants (6-17 years of age) will will receive alpelisib at the dose selected for confirmatory phase in pediatric participants; and pediatric participants of 0-5 years of age will receive dose 3 of alpelisib

Intervention Type DRUG

Placebo

In Stage 2, participants will receive matching placebo for 24 weeks of the study

Intervention Type DRUG

Other Intervention Names

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BYL719

Eligibility Criteria

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Inclusion Criteria

1. Signed informed consent and assent (when applicable) from the participant, parent, legal authorized representative or guardian.
2. Participant must be willing to remain at the clinical site as required by the protocol and be willing to adhere to study restrictions and examination schedules.
3. Participant has a physician confirmed and documented diagnosis of a symptomatic LyM at the time of informed consent (Note: the physician must confirm that the LyM cannot be included under the PROS diagnostic criteria).
4. Participant is not considered as a candidate for or is not willing to receive non-drug therapies including but not limited to sclerotherapy, embolization, and surgery until the completion of Week 24 in Stage 1 and 2.
5. Participant has evidence of a somatic mutation(s) in the PIK3CA gene prior to randomization.
6. Participant has at least one measurable LyM lesion confirmed by BIRC assessment prior to randomization.
7. Participants must be able to ingest study drug (either in tablet form or as a drinkable suspension \[Groups 1 to 4\] or granules or as an oral suspension \[Group 5\]) as assessed within 7 days before study treatment start. Drug administration via feeding tubes is allowed.

Exclusion Criteria

1. Participant has a physician-confirmed and documented diagnosis of PROS at the time of informed consent.
2. Participant has a physician-confirmed and documented diagnosis of a Central Conducting Lymphatic Anomaly, General Lymphatic Anomaly, Gorham-Stout disease, Kaposiform lymphangiomatosis at the time of informed consent.
3. Participant has a known history of Stevens-Johnson syndrome, erythema multiforme, or toxic epidermal necrolysis at the time of informed consent.
4. Participant has an established diagnosis of type I diabetes mellitus or uncontrolled type II diabetes mellitus at the time of informed consent.
5. Participant had previous treatment with alpelisib and/or any other PI3K inhibitors with treatment duration longer than 2 weeks at the time of informed consent.
Minimum Eligible Age

0 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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UCSF Benioff Children s Hospital

Oakland, California, United States

Site Status RECRUITING

Lucile Packard Childrens Hosp

Palo Alto, California, United States

Site Status RECRUITING

Childrens National Medical Center

Washington D.C., District of Columbia, United States

Site Status RECRUITING

Childrens Hosp Boston Dept of Heme

Boston, Massachusetts, United States

Site Status RECRUITING

WA Uni School Of Med

St Louis, Missouri, United States

Site Status RECRUITING

Cinn Children Hosp Medical Center

Cincinnati, Ohio, United States

Site Status RECRUITING

Univ Hospital Of Cleveland

Cleveland, Ohio, United States

Site Status RECRUITING

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status RECRUITING

Oregon Health Science University

Portland, Oregon, United States

Site Status RECRUITING

CHOP Abramson Pediatric Resch Ctr

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Baylor College Of Medicine

Houston, Texas, United States

Site Status RECRUITING

U of TX Health Science Ct

Houston, Texas, United States

Site Status RECRUITING

Childrens Hospital and Regional Medical Center

Seattle, Washington, United States

Site Status RECRUITING

Novartis Investigative Site

Sydney, New South Wales, Australia

Site Status RECRUITING

Novartis Investigative Site

Sydney, New South Wales, Australia

Site Status RECRUITING

Novartis Investigative Site

Brisbane, Queensland, Australia

Site Status RECRUITING

Novartis Investigative Site

Brussels, , Belgium

Site Status RECRUITING

Novartis Investigative Site

Bordeaux, , France

Site Status RECRUITING

Novartis Investigative Site

Bron, , France

Site Status RECRUITING

Novartis Investigative Site

Caen, , France

Site Status RECRUITING

Novartis Investigative Site

Dijon, , France

Site Status RECRUITING

Novartis Investigative Site

Lille, , France

Site Status RECRUITING

Novartis Investigative Site

Marseille, , France

Site Status RECRUITING

Novartis Investigative Site

Montpellier, , France

Site Status RECRUITING

Novartis Investigative Site

Paris, , France

Site Status RECRUITING

Novartis Investigative Site

Paris, , France

Site Status RECRUITING

Novartis Investigative Site

Tours, , France

Site Status RECRUITING

Novartis Investigative Site

Freiburg im Breisgau, Baden-Wurttemberg, Germany

Site Status RECRUITING

Novartis Investigative Site

Mannheim, Baden-Wurttemberg, Germany

Site Status RECRUITING

Novartis Investigative Site

Cologne, North Rhine-Westphalia, Germany

Site Status RECRUITING

Novartis Investigative Site

Leipzig, Saxony, Germany

Site Status RECRUITING

Novartis Investigative Site

Berlin, , Germany

Site Status RECRUITING

Novartis Investigative Site

Bologna, BO, Italy

Site Status RECRUITING

Novartis Investigative Site

Milan, MI, Italy

Site Status RECRUITING

Novartis Investigative Site

Roma, RM, Italy

Site Status RECRUITING

Novartis Investigative Site

Roma, RM, Italy

Site Status RECRUITING

Novartis Investigative Site

Napoli, , Italy

Site Status RECRUITING

Novartis Investigative Site

Esplugues, Barcelona, Spain

Site Status RECRUITING

Novartis Investigative Site

A Coruña, , Spain

Site Status RECRUITING

Novartis Investigative Site

Madrid, , Spain

Site Status RECRUITING

Novartis Investigative Site

Madrid, , Spain

Site Status RECRUITING

Countries

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United States Australia Belgium France Germany Italy Spain

Central Contacts

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Novartis Pharmaceuticals

Role: CONTACT

Phone: 1-888-669-6682

Email: [email protected]

Novartis Pharmaceuticals

Role: CONTACT

Phone: +41613241111

Email: [email protected]

Facility Contacts

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Audrey Hernando

Role: primary

Ramrada Lekwuttikarn

Role: primary

Taylor Brice

Role: primary

Kelsey Deemer

Role: primary

Sally Jones

Role: primary

Kimberly Whittaker

Role: primary

Hayley Sluka

Role: primary

Bea Ferreira Alves

Role: primary

Denae Clohessy

Role: primary

Samantha Santos

Role: primary

Derek Cole

Role: primary

Janaei Phillips

Role: primary

Maya Gopalan

Role: primary

Other Identifiers

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2023-504146-60-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

CBYL719P12201

Identifier Type: -

Identifier Source: org_study_id