Novartis Investigative Site 79106 Freiburg (Baden-Württemberg) GermanyRekrutierend» Google-MapsLucile Packard Childrens Hosp . 94304 Palo Alto United StatesRekrutierend» Google-MapsWashington Uni School of Med Pediatric Hem-Onc 63110 Saint Louis United StatesRekrutierend» Google-Maps Ansprechpartner: Katie Schultz E-Mail: Katie.schultz@wustl.edu» Ansprechpartner anzeigen
Novartis Investigative Site 4101 Brisbane AustraliaRekrutierend» Google-MapsNovartis Investigative Site 69677 Bron Cedex FranceRekrutierend» Google-MapsNovartis Investigative Site 14033 Caen FranceRekrutierend» Google-MapsNovartis Investigative Site 13885 Marseille Cedex 05 FranceRekrutierend» Google-MapsNovartis Investigative Site 34295 Montpellier Cedex FranceRekrutierend» Google-MapsNovartis Investigative Site 37044 Tours 9 FranceRekrutierend» Google-MapsNovartis Investigative Site 28046 Madrid SpainRekrutierend» Google-Maps
1. Stage 2:Radiological response rate at Week 24 of Stage 2 (adult and pediatric (6 - 17 years of age) participants) (Time Frame - Baseline, Week 24): 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
Secondary outcome:
1. 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) (Time Frame - Baseline, Week 24): 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
2. Stage 2: Percentage of participants with a radiological response at Week 24 of Stage 2 (pediatric participants 2-5 years of age) (Time Frame - Baseline, Week 24): 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 2-5 years of age will be assessed
3. Stage 2: Change from baseline in patient global impression of change (PGI-C) scale (adult and pediatric (6-17 years of age) participants) (Time Frame - Up to approximately 6 years): 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
4. Stage 2: Change from baseline in patient-reported outcomes measurement information system (PROMIS) profile domains(adult and pediatric (6-17 years of age) participants) (Time Frame - Up to approximately 6 years): 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 internsity 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
5. Stage 2: Change from baseline in investigator global impression of change (IGIC) scale (adult and pediatric (6-17 years of age) participants) (Time Frame - Up to approximately 6 years): 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
6. Stage 2: Change from baseline in health utilities of the EuroQol 5-dimension (EQ-5D) (adult and pediatric (6-17 years of age) participants) (Time Frame - Up to approximately 6 years): 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
7. Duration of response (DOR) in adult and pediatric participants who receive alpelisib (Stage 1 and 2) (Time Frame - Up to approximately 6 years): 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.
8. Radiological response rate of alpelisib in adult and pediatric (6-17 years of age) participants (Stage 1) (Time Frame - Baseline, Week 24): 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.
9. Radiological response rate of alpelisib in adult and pediatric participants (Stage 1 and 2) (Time Frame - Up to approximately 6 years): 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.
10. Alpelisib plasma concentrations (Stage 1 and 2) (Time Frame - On Day 1 of Week 8, 16, 24, 48 and 120): Alpelisib plasma concentrations in adult and pediatric participants (Stage 1 and 2).
11. 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) (Time Frame - 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)
12. Percentage of participants with of LyM-related symptoms, complications, and comorbidities on treatment with alpelisib in adult and pediatric participants (Stage 1 and 2) (Time Frame - Up to approximately 6 years): Percentage of participants with of LyM-related symptoms, complications, and comorbidities on treatment with alpelisib in adult and pediatric participants (Stage 1 and 2)
13. Change from baseline in LyM lesions in adult and pediatric participants at Week 24 (Stage 1 and 2) (Time Frame - Baseline, 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)
14. Change from baseline in LyM lesions in adult and pediatric participants (Stage 1 and 2) (Time Frame - Up to approximately 6 years): 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)
15. Percentage of participants with changes in non-target lesions in adult and pediatric participants at Week 24 (Stage 1 and 2) (Time Frame - Baseline, 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)
16. Percentage of participants with changes in non-target lesions in adult and pediatric participants (Stage 1 and 2) (Time Frame - Up to approximately 6 years): Percentage of participants with changes in non-target lesions as assessed by BIRC in adult and pediatric participants (Stage 1 and 2)
17. Percentage of participants with new lesions in adult and pediatric participants at Week 24 (Stage 1 and 2) (Time Frame - Baseline, 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)
18. Percentage of participants with new lesions in adult and pediatric participants (Stage 1 and 2) (Time Frame - Up to approximately 6 years): The percentage of participants with new lesions as assessed by BIRC in adult and pediatric participants (Stage 1 and 2)
Experimental: 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)
Experimental: 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).
Experimental: 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)
Experimental: 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).
Experimental: 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)
Placebo Comparator: Adult participants, placebo (Stage 2) Adult participants (≥18 years of age) who will receive matching placebo
Experimental: 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)
Placebo Comparator: Pediatric participants (6-17 years of age), placebo (Stage 2) Pediatric participants (6-17 years of age) who will receive matching placebo
Experimental: Pediatric participants (2-5 years of age), alpelisib (Stage 2) Pediatric participants of 2-5 years who will dose 3 of alpelisib in an open-label fashion for at least 24 weeks unless they discontinue earlier
Alpelisib (BYL719): 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 recieve 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 2-5 years of age will receive dose 3 of alpelisib
Placebo: In Stage 2, participants will receive matching placebo for 24 weeks of the study
Quelle: ClinicalTrials.gov
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"Alpelisib in Pediatric and Adult Patients With Lymphatic Malformations Associated With a PIK3CA Mutation."
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