Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2023-504146-60-00 | Registry Identifier | EU CTIS number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
This is a phase II/III multi-center study with two stages:
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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) |
|
| 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). |
|
| 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) |
|
| 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). |
|
| 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) |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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) | PGI-S is a single item measure to assess the overall severity of a patient's condition. This single item instrument uses a 5-point rating scale, which ranges from 1 (no symptoms) to 5 (very severe). Lower scores indicate better health status. The percentage of participants with at least a 1-point improvement compared to baseline at Week 24 of Stage 2 in adult and pediatric (6-17 years of age) groups will be assessed |
Not provided
Key inclusion criteria:
Key exclusion criteria:
Other inclusion/exclusion criteria may apply
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Novartis Pharmaceuticals | Contact | 1-888-669-6682 | novartis.email@novartis.com | |
| Novartis Pharmaceuticals | Contact | +41613241111 | novartis.email@novartis.com |
| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCSF Benioff Children s Hospital | Recruiting | Oakland | California | 94609 | United States |
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Adult participants, placebo (Stage 2) | Placebo Comparator | Adult participants (≥18 years of age) who will receive matching 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) |
|
| Pediatric participants (6-17 years of age), placebo (Stage 2) | Placebo Comparator | Pediatric participants (6-17 years of age) who will receive matching 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 |
|
|
|
| Placebo | Drug | In Stage 2, participants will receive matching placebo for 24 weeks of the study |
|
| 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) | 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 pediatric participants 0-5 years of age will be assessed | 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) | PGI-C is a single item measure to assess the change in overall symptoms severity since the start of study. This single item instrument uses a 7-point rating scale, which ranges from 1 (very much improved) to 7 (very much worse). Lower scores indicate better health status. The change from baseline in PGI-C score will be assessed in 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) | The PROMIS-29 plus 2 Profile v2.1 (completed by adult participant) includes 29 items across domains of depression, anxiety, physical function, pain interference, fatigue, sleep disturbance, ability to participant in social roles and activities, cognitive function abilities and pain intensity. The PROMIS Pediatric-25 Profile v2.0 (completed by children over 8 years of age) and PROMIS Parent-Proxy-25 Profile v2.0 (completed by parents for children under 8 years of age) include 25 items across the domains of depressive symptoms, anxiety, physical function-mobility, pain interference, fatigue, and peer relationships and pain intensity All items (except the pain intensity item) use a 5-point Likert scale, which ranges from 1 (not at all) to 5 (very much). The pain intensity item is scored on a 0-10 numeric rating scale, where 0 represents "no pain" and 10 represents "worst imaginable pain". The change from baseline in PROMIS domains will be assessed | 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) | The IGIC involves a single question that asks the investigator to rate the change in the patient's condition since the start of treatment or intervention, using a 7-point scale ranging from 1 (Very much improved) to 7 (Very much worse). The change from baseline in IGIC score will be assessed in adult and pediatric (6-17 years of age) participants | Up to approximately 8 years |
| Stage 2: Change from baseline in health utilities of the EuroQol 5-dimension (EQ-5D) (adult and pediatric (6-17 years of age) participants) | The EQ-5D-5L (completed by adult participants) includes 5 items addressing dimensions of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each with 5 response options, ranging from 1=no problems to 5=extreme problems The EQ-5D-Y (completed by children over 8 years of age) and EQ-5D-Y Proxy version (completed by parent for participants under 8 years of age or unable to record for themselves) includes 5 items addressing dimensions of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each with 3 response options, ranging from 1= no problems to 3= a lot of problems | Up to approximately 8 years |
| Stage 1 and 2: Duration of response (DOR) in adult and pediatric participants who receive alpelisib | DOR is defined as the time from first documented response until progression of LyM lesions by BIRC or death. This analysis only applies to participants who are on treatment with alpelisib (Stage 1 and 2) and who achieve response. | Up to approximately 8 years |
| Stage 1: Radiological response rate of alpelisib in 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 (adult and pediatric 6-17 years of age) with radiological response at Week 24 of Stage 1 will be assessed. | Baseline, Week 24 |
| Stage 1 and 2: Radiological response rate of alpelisib in adult and pediatric 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, 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 who receive alpelisib (Stage 1 and 2) with radiological response will be assessed. | Up to approximately 8 years |
| Stage 1 and 2: Alpelisib plasma concentrations | Alpelisib plasma concentrations in adult and pediatric participants (Stage 1 and 2). | On Day 1 of Week 8, 16, 24, 48 and 120 |
| Stage 1 and 2: Percentage of participants with of LyM-related symptoms, complications, and comorbidities on treatment with alpelisib in adult and pediatric participants at Week 24 | Percentage of participants with of LyM-related symptoms, complications, and comorbidities on treatment with alpelisib in adult and pediatric participants at Week 24 (Stage 1 and 2) | Week 24 |
| Stage 1 and 2: Percentage of participants with of LyM-related symptoms, complications, and comorbidities on treatment with alpelisib in adult and pediatric participants | Percentage of participants with of LyM-related symptoms, complications, and comorbidities on treatment with alpelisib in adult and pediatric participants (Stage 1 and 2) | Up to approximately 8 years |
| Stage 1 and 2: Change from baseline in LyM lesions in adult and pediatric participants at Week 24 | Change from baseline in the sum of target lesion volumes, the sum of MRI-measurable non-target lesion (if applicable) volumes, and the sum of all MRI-measurable lesion (target and non-target) volumes as assessed by BIRC at Week 24 in adult and pediatric participants (Stage 1 and 2) | Baseline, Week 24 |
| Stage 1 and 2: Change from baseline in LyM lesions in adult and pediatric participants | Change from baseline in the sum of target lesion volumes, the sum of MRI-measurable non-target lesion (if applicable) volumes, and the sum of all MRI-measurable lesion (target and non-target) volumes as assessed by BIRC in adult and pediatric participants (Stage 1 and 2) | Up to approximately 8 years |
| Stage 1 and 2: Percentage of participants with changes in non-target lesions in adult and pediatric participants at Week 24 | Percentage of participants with changes in non-target lesions as assessed by BIRC at Week 24 in adult and pediatric participants (Stage 1 and 2) | Baseline, Week 24 |
| Stage 1 and 2: Percentage of participants with changes in non-target lesions in adult and pediatric participants | Percentage of participants with changes in non-target lesions as assessed by BIRC in adult and pediatric participants (Stage 1 and 2) | Up to approximately 8 years |
| Stage 1 and 2: Percentage of participants with new lesions in adult and pediatric participants at Week 24 | The percentage of participants with new lesions as assessed by BIRC at Week 24 in adult and pediatric participants (Stage 1 and 2) | Baseline, Week 24 |
| Stage 1 and 2: Percentage of participants with new lesions in adult and pediatric participants | The percentage of participants with new lesions as assessed by BIRC in adult and pediatric participants (Stage 1 and 2) | Up to approximately 8 years |
| Lucile Packard Childrens Hosp | Recruiting | Palo Alto | California | 94304 | United States |
|
| Childrens National Medical Center | Recruiting | Washington D.C. | District of Columbia | 20010-2970 | United States |
|
| Nemours Childrens Clinic | Recruiting | Jacksonville | Florida | 32207 | United States |
|
| Childrens Hosp Boston Dept of Heme | Recruiting | Boston | Massachusetts | 02115 | United States |
|
| WA Uni School Of Med | Recruiting | St Louis | Missouri | 63110 | United States |
|
| UNC Chapel Hill | Recruiting | Chapel Hill | North Carolina | 27599 | United States |
|
| Cinn Children Hosp Medical Center | Recruiting | Cincinnati | Ohio | 45229-3039 | United States |
|
| Univ Hospital Of Cleveland | Recruiting | Cleveland | Ohio | 44106 | United States |
|
| Cleveland Clinic Foundation | Recruiting | Cleveland | Ohio | 44195 | United States |
|
| Nationwide Children s Hospital | Recruiting | Columbus | Ohio | 43205 | United States |
|
| Oregon Health Science University | Recruiting | Portland | Oregon | 97239 | United States |
|
| CHOP Abramson Pediatric Resch Ctr | Recruiting | Philadelphia | Pennsylvania | 19104 | United States |
|
| Childrens Hosp Pittsburgh UPMC | Recruiting | Pittsburgh | Pennsylvania | 15224 | United States |
|
| Baylor College Of Medicine | Recruiting | Houston | Texas | 77030 | United States |
|
| U of TX Health Science Ct | Recruiting | Houston | Texas | 77030 | United States |
|
| Childrens Hospital and Regional Medical Center | Recruiting | Seattle | Washington | 98105 | United States |
|
| Novartis Investigative Site | Recruiting | CABA | Buenos Aires | C1181ACH | Argentina |
| Novartis Investigative Site | Recruiting | CABA | Buenos Aires | C1425BEA | Argentina |
| Novartis Investigative Site | Recruiting | Capital Federal | C1023AAB | Argentina |
| Novartis Investigative Site | Recruiting | Sydney | New South Wales | 2010 | Australia |
| Novartis Investigative Site | Recruiting | Sydney | New South Wales | 2031 | Australia |
| Novartis Investigative Site | Recruiting | Brisbane | Queensland | 4101 | Australia |
| Novartis Investigative Site | Recruiting | Brussels | 1200 | Belgium |
| Novartis Investigative Site | Recruiting | Brno | 625 00 | Czechia |
| Novartis Investigative Site | Recruiting | Angers | 49933 | France |
| Novartis Investigative Site | Recruiting | Bordeaux | 33076 | France |
| Novartis Investigative Site | Recruiting | Bron | 69677 | France |
| Novartis Investigative Site | Recruiting | Caen | 14033 | France |
| Novartis Investigative Site | Recruiting | Dijon | 21000 | France |
| Novartis Investigative Site | Recruiting | Lille | 59000 | France |
| Novartis Investigative Site | Recruiting | Marseille | 13885 | France |
| Novartis Investigative Site | Recruiting | Montpellier | 34295 | France |
| Novartis Investigative Site | Recruiting | Paris | 75010 | France |
| Novartis Investigative Site | Recruiting | Paris | 75015 | France |
| Novartis Investigative Site | Recruiting | Toulouse | 31054 | France |
| Novartis Investigative Site | Recruiting | Tours | 37044 | France |
| Novartis Investigative Site | Recruiting | Freiburg im Breisgau | Baden-Wurttemberg | 79106 | Germany |
| Novartis Investigative Site | Withdrawn | Mannheim | Baden-Wurttemberg | 68305 | Germany |
| Novartis Investigative Site | Recruiting | Cologne | North Rhine-Westphalia | 50937 | Germany |
| Novartis Investigative Site | Recruiting | Leipzig | Saxony | 04103 | Germany |
| Novartis Investigative Site | Recruiting | Berlin | 13353 | Germany |
| Novartis Investigative Site | Recruiting | Ulm | 89081 | Germany |
| Novartis Investigative Site | Recruiting | Bologna | BO | 40138 | Italy |
| Novartis Investigative Site | Recruiting | Milan | MI | 20122 | Italy |
| Novartis Investigative Site | Recruiting | Roma | RM | 00165 | Italy |
| Novartis Investigative Site | Recruiting | Roma | RM | 00168 | Italy |
| Novartis Investigative Site | Recruiting | Torino | TO | 10126 | Italy |
| Novartis Investigative Site | Recruiting | Naples | 80122 | Italy |
| Novartis Investigative Site | Recruiting | Nijmegen | Gelderland | 6500HB | Netherlands |
| Novartis Investigative Site | Recruiting | Rotterdam | South Holland | 3015 GD | Netherlands |
| Novartis Investigative Site | Recruiting | Palma | Balearic Islands | 07120 | Spain |
| Novartis Investigative Site | Recruiting | Esplugues | Barcelona | 08950 | Spain |
| Novartis Investigative Site | Recruiting | L'Hospitalet de Llobregat | Barcelona | 08907 | Spain |
| Novartis Investigative Site | Recruiting | A Coruña | 15006 | Spain |
| Novartis Investigative Site | Recruiting | Barcelona | 08035 | Spain |
| Novartis Investigative Site | Recruiting | Madrid | 28009 | Spain |
| Novartis Investigative Site | Recruiting | Madrid | 28046 | Spain |
| Novartis Investigative Site | Recruiting | Lausanne | 1011 | Switzerland |
| ID | Term |
|---|---|
| D044148 | Lymphatic Abnormalities |
| D018191 | Lymphangioma, Cystic |
| D008202 | Lymphangioma |
| ID | Term |
|---|---|
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D018190 | Neoplasm, Lymphatic Tissue |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
Not provided
Not provided
| ID | Term |
|---|---|
| C585539 | Alpelisib |
Not provided
Not provided
Not provided