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

NCT05948943 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: CBYL719P122012023-504146-60-00
• Study Type: interventional
• Target: 232
• Locations: 10 countries
• Sites: 54

Brief Summary

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.

Conditions

Lymphatic Malformations

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Stage 2:Radiological response rate at Week 24 of Stage 2 (adult and pediatric (6 - 17 years of age) participants)

  Radiological response defined by achieving at least 20% reduction in the sum of target lesion volumes (1 to 3 lesions), assessed by MRI by a BIRC at Week 24, provided that none of the individual target lesions has at least 20% increase from baseline and in absence of progression of non-target lesions and without new lesions. The percentage of participants with a radiological response at Week 24 of Stage 2 in adult and pediatric (6-17 years of age) groups will be assessed

  Baseline, Week 24

Secondary Outcomes (18)

• Stage 2: Percentage of participants with at least a 1-point improvement compared to baseline based on patient global impression of severity (PGI-S) scale at Week 24 of Stage 2 (adult and pediatric (6 - 17 years of age) participants)

  Baseline, Week 24

• Stage 2: Percentage of participants with a radiological response at Week 24 of Stage 2 (pediatric participants 0-5 years of age)

  Baseline, Week 24

• Stage 2: Change from baseline in patient global impression of change (PGI-C) scale (adult and pediatric (6-17 years of age) participants)

  Up to approximately 8 years

• Stage 2: Change from baseline in patient-reported outcomes measurement information system (PROMIS) profile domains(adult and pediatric (6-17 years of age) participants)

  Up to approximately 8 years

• Stage 2: Change from baseline in investigator global impression of change (IGIC) scale (adult and pediatric (6-17 years of age) participants)

  Up to approximately 8 years

Study Arms (9)

Adult participants, alpelisib dose 1 (Stage 1)

EXPERIMENTAL

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)

Drug: Alpelisib

Adult participants, alpelisib dose 2 (Stage 1)

EXPERIMENTAL

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).

Drug: Alpelisib

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

EXPERIMENTAL

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)

Drug: Alpelisib

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

EXPERIMENTAL

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).

Drug: Alpelisib

Adult participants, alpelisib (Stage 2)

EXPERIMENTAL

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

Drug: Alpelisib

Adult participants, placebo (Stage 2)

PLACEBO COMPARATOR

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

Drug: Placebo

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

EXPERIMENTAL

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

Drug: Alpelisib

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

PLACEBO COMPARATOR

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

Drug: Placebo

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

EXPERIMENTAL

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

Drug: Alpelisib

Interventions

Alpelisib 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

Also known as: BYL719

Adult participants, alpelisib (Stage 2); Adult participants, alpelisib dose 1 (Stage 1); Adult participants, alpelisib dose 2 (Stage 1); Pediatric participants (0-5 years of age), alpelisib (Stage 2); Pediatric participants (6-17 years of age), alpelisib (Stage 2); Pediatric participants (6-17 years of age), alpelisib dose 2 (Stage 1); Pediatric participants (6-17 years of age), alpelisib dose 3 (Stage 1)

Placebo DRUG

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

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

Eligibility Criteria

• Age: 0 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent and assent (when applicable) from the participant, parent, legal authorized representative or guardian.
• 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.
• 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).
• 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.
• Participant has evidence of a somatic mutation(s) in the PIK3CA gene prior to randomization.
• Participant has at least one measurable LyM lesion confirmed by BIRC assessment prior to randomization.
• 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.

You may not qualify if:

• Participant has a physician-confirmed and documented diagnosis of PROS at the time of informed consent.
• 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.
• Participant has a known history of Stevens-Johnson syndrome, erythema multiforme, or toxic epidermal necrolysis at the time of informed consent.
• Participant has an established diagnosis of type I diabetes mellitus or uncontrolled type II diabetes mellitus at the time of informed consent.
• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (54)

UCSF Benioff Children s Hospital

Oakland, California, 94609, United States

RECRUITING

Lucile Packard Childrens Hosp

Palo Alto, California, 94304, United States

RECRUITING

Childrens National Medical Center

Washington D.C., District of Columbia, 20010-2970, United States

RECRUITING

Nemours Childrens Clinic

Jacksonville, Florida, 32207, United States

RECRUITING

Childrens Hosp Boston Dept of Heme

Boston, Massachusetts, 02115, United States

RECRUITING

WA Uni School Of Med

St Louis, Missouri, 63110, United States

RECRUITING

Cinn Children Hosp Medical Center

Cincinnati, Ohio, 45206, United States

RECRUITING

Univ Hospital Of Cleveland

Cleveland, Ohio, 44106, United States

RECRUITING

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

RECRUITING

Nationwide Children s Hospital

Columbus, Ohio, 43205, United States

RECRUITING

Oregon Health Science University

Portland, Oregon, 97239, United States

RECRUITING

CHOP Abramson Pediatric Resch Ctr

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Childrens Hosp Pittsburgh UPMC

Pittsburgh, Pennsylvania, 15224, United States

RECRUITING

Baylor College Of Medicine

Houston, Texas, 77030, United States

RECRUITING

U of TX Health Science Ct

Houston, Texas, 77030, United States

RECRUITING

Childrens Hospital and Regional Medical Center

Seattle, Washington, 98105, United States

RECRUITING

Novartis Investigative Site

CABA, Buenos Aires, C1181ACH, Argentina

RECRUITING

Novartis Investigative Site

CABA, Buenos Aires, C1425BEA, Argentina

RECRUITING

Novartis Investigative Site

Capital Federal, C1023AAB, Argentina

RECRUITING

Novartis Investigative Site

Sydney, New South Wales, 2010, Australia

RECRUITING

Novartis Investigative Site

Sydney, New South Wales, 2031, Australia

RECRUITING

Novartis Investigative Site

Brisbane, Queensland, 4101, Australia

RECRUITING

Novartis Investigative Site

Brussels, 1200, Belgium

RECRUITING

Novartis Investigative Site

Angers, 49933, France

RECRUITING

Novartis Investigative Site

Bordeaux, 33076, France

RECRUITING

Novartis Investigative Site

Bron, 69677, France

RECRUITING

Novartis Investigative Site

Caen, 14033, France

RECRUITING

Novartis Investigative Site

Dijon, 21000, France

RECRUITING

Novartis Investigative Site

Lille, 59000, France

RECRUITING

Novartis Investigative Site

Marseille, 13885, France

RECRUITING

Novartis Investigative Site

Montpellier, 34295, France

RECRUITING

Novartis Investigative Site

Paris, 75010, France

RECRUITING

Novartis Investigative Site

Paris, 75015, France

RECRUITING

Novartis Investigative Site

Toulouse, 31054, France

RECRUITING

Novartis Investigative Site

Tours, 37044, France

RECRUITING

Novartis Investigative Site

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

RECRUITING

Novartis Investigative Site

Mannheim, Baden-Wurttemberg, 68305, Germany

WITHDRAWN

Novartis Investigative Site

Cologne, North Rhine-Westphalia, 50937, Germany

RECRUITING

Novartis Investigative Site

Leipzig, Saxony, 04103, Germany

RECRUITING

Novartis Investigative Site

Berlin, 13353, Germany

RECRUITING

Novartis Investigative Site

Bologna, BO, 40138, Italy

RECRUITING

Novartis Investigative Site

Milan, MI, 20122, Italy

RECRUITING

Novartis Investigative Site

Roma, RM, 00165, Italy

RECRUITING

Novartis Investigative Site

Roma, RM, 00168, Italy

RECRUITING

Novartis Investigative Site

Torino, TO, 10126, Italy

RECRUITING

Novartis Investigative Site

Naples, 80122, Italy

RECRUITING

Novartis Investigative Site

Nijmegen, Gelderland, 6500HB, Netherlands

RECRUITING

Novartis Investigative Site

Rotterdam, South Holland, 3015 GD, Netherlands

RECRUITING

Novartis Investigative Site

Palma, Balearic Islands, 07120, Spain

RECRUITING

Novartis Investigative Site

Esplugues, Barcelona, 08950, Spain

RECRUITING

Novartis Investigative Site

A Coruña, 15006, Spain

RECRUITING

Novartis Investigative Site

Madrid, 28009, Spain

RECRUITING

Novartis Investigative Site

Madrid, 28046, Spain

RECRUITING

Novartis Investigative Site

Lausanne, 1011, Switzerland

RECRUITING

MeSH Terms

Conditions

Lymphatic Abnormalities; Lymphangioma, Cystic; Lymphangioma

Interventions

Alpelisib

Condition Hierarchy (Ancestors)

Lymphatic Diseases; Hemic and Lymphatic Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neoplasm, Lymphatic Tissue; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

Novartis Pharmaceuticals

CONTACT

1-888-669-6682; novartis.email@novartis.com

Novartis Pharmaceuticals

CONTACT

+41613241111; novartis.email@novartis.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: July 4, 2023
• First Posted: July 17, 2023
• Study Start: November 24, 2023
• Primary Completion (Estimated): May 31, 2028
• Study Completion (Estimated): May 2, 2033
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

DE (5); IT (6); NL (2); ES (5); US (16); FR (12); BE (1); AU (3); AR (3); CH (1)