E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Multiple Myeloma |
Myélome multiple |
|
E.1.1.1 | Medical condition in easily understood language |
Cancer of plasma cells |
Cancer des cellules plasmatiques |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028228 |
E.1.2 | Term | Multiple myeloma |
E.1.2 | System Organ Class | 100000004864 |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
- To assess overall response rate (ORR) up to 8 cycles |
Evaluer le taux de réponse global (TRG) jusqu’à 8 cycles |
|
E.2.2 | Secondary objectives of the trial |
- To assess overall response rate (ORR) - To assess the individual iCR, sCR, CR, VGPR rates - To assess progression free survival (PFS) - To assess overall survival (OS) - To evaluate overall safety of the combination of PAN, BTZ and Dex - To assess pharmacokinetics - To assess exposure-response (efficacy and safety) relationship - To assess Time to Progression (TTP), Time to Response (TTR), Duration of Response (DOR) - To assess health-related quality of life (HRQoL) |
- Evaluer le TRG - Evaluer les taux individuels de RCi, RCs, RC, TBRP - Evaluer la survie sans progression (SSP) - Evaluer la survie globale (SG) - Evaluer la tolérance globale de l’association PAN, BTZ et Dex - Evaluer la pharmacocinétique (PK) - Evaluer le lien exposition-réponse (efficacité et tolérance) - Evaluer le temps jusqu’à la progression (TAP), le temps de réponse (TR), la durée de réponse (DR) - Evaluer la qualité de vie liée à la santé (HRQoL) |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Multiple Myeloma as per IMWG 2014 definition - Requiring treatment for relapsed or relapsed/refractory disease - Measurable disease based on central protein assessment - 1 to 4 prior lines of therapy - Prior IMiD exposure - Acceptable lab values prior to starting study treatment Other protocol-defined inclusion criteria may apply. |
- Myélome multiple selon la définition IMWG 2014 - Nécessite un traitement pour une maladie en recuchute ou réfractaire - Maladie mesurable basée sur l'évaluation de la protéine centrale - 1 à 4 traitements antérieurs - Une exposition préalable IMiD - Les valeurs de laboratoire acceptable avant de commencer le traitement à l'étude Autres critères d'inclusion définis par le protocole d'utilisation. |
|
E.4 | Principal exclusion criteria |
- Primary refractory myeloma - Refractory to bortezomib i.e. patients who progressed while receiving salvage therapy with BTZ, or patients who progressed within 60 days of their most recent BTZ containing treatment. - Concomitant anti-cancer therapy (other than BTZ/Dex and bisphosphonates) - Prior treatment with DAC inhibitors - Clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 month prior to screening) - Unresolved diarrhea ≥ CTCAE grade 2 or presence of medical condition associated with chronic diarrhea (such as irritable bowel syndrome, inflammatory bowel disease) Other protocol-defined exclusion criteria may apply. |
- Myélome primitif réfractaire - Réfractaire au bortézomib c'est-à-dire aux patients qui ont progressé tout en recevant un traitement de rattrapage avec BTZ, ou aux patients qui ont progressé dans les 60 jours suivant leur dernier traitement contenant du BTZ. - traitement anti-cancereux concomitant (autre que BTZ / Dex et bisphosphonates) - Un traitement antérieur par des inhibiteurs de DAC - Cardiopathie cliniquement significative, non contrôlée et/ou évènement cardiaque récent (durant les 6 mois précédant la sélection), - Diarrhée persistante de grade CTCAE ≥ 2 ou être atteint d’une maladie associée à des diarrhées chroniques (telle que le syndrome du côlon irritable, la maladie intestinale inflammatoire) Autres critères d'exclusion définis par le protocole d'utilisation. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
ORR (according to IMWG criteria by IRC assessment) comprised of immunophenotypic CR (iCR), stringent Complete Response (sCR), Complete Response (CR), Very Good Partial Response (VGPR) and Partial Response (PR) |
TRG selon les critères du groupe international de travail sur le myélome (IMWG) (évalué par un comité d'évaluation indépendant (IRC)) y compris : réponse complète immunophénotypique (RCi), réponse complète stricte (RCs), réponse complète (RC), très bonne réponse partielle (TBRP) et réponse partielle (RP)
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Approximately after 30 months |
Après environ 30 mois |
|
E.5.2 | Secondary end point(s) |
- ORR (according to IMWG criteria by IRC assessment) - iCR, sCR, CR, VGPR rates (according to IMWG criteria by IRC assessment) - PFS (according to IMWG criteria by IRC assessment) - OS - AEs (graded by CTCAE v4.03), SAEs Abnormalities in vital signs, ECG parameters, and laboratory test values. This will include events up to 30 days after discontinuation of study treatment. - Cmax (PAN, BTZ), C24h (PAN), Cmin (BTZ) and AUC0-8h (PAN, BTZ) - ORR, Grade 3/4 Thrombocytopenia, Grade 3/4 Diarrhea (relationship with PAN, BTZ PK parameters derived from NCA or Pop PK analysis) - TTP, TTR, DOR (according to IMWG criteria by IRC assessment) - HRQoL as measured by EORTC QLQ-C30 and FACT/GOG-Ntx |
-TRG (selon les critères IMWG) évalué par l’IRC - Taux de RCi, RCs, RC, TBRP (selon les critères IMWG) évalué par l’IRC - SSP (selon les critères IMWG) évalué par l’IRC - SG - Effets indésirables selon les critères de terminologie communs pour les effets indésirables (CTCAE v.4.03), effets indésirables graves, anomalies des signes vitaux, des paramètres électrocardiographiques (à l’ECG), et des bilans biologiques. Les effets indésirables seront consignés jusqu’à 30 jours après l’arrêt du traitement - Cmax (PAN, BTZ), C24h (PAN), Cmin (BTZ) et AUC0-8h (PAN, BTZ) - TRG, thrombocytopénie de grade 3/4, diarrhée de grade 3/4 (la relation avec les paramètres PK de PAN, BTZ dérivés des analyses PK non-compartimentées [NCA] ou les autres analyses PK) - TAP, TR, DR (selon les critères IMWG) évalué par l’IRC) - HRQoL mesurée par EORTC QLQ-C30 and FACT/GOG-Ntx |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
- best ORR: approximately after 70 months - individual iCR, sCR, CR, VGPR rates: approximatively after 30 and 70 months - PFS: approximatively after 30 and 70 months - OS: approximatively after 30 and 70 months - Overall safety of combination of PAN, BTZ and Dex: approximatively after 30 and 70 months - Pharmacokinetics: approximatively after 30 months - Exposure-response:a pproximatively after 30 months - TTP, TTR, DOR: approximatively after 30 and 70 months - HRQoL: approximatively after 30 and 70 months |
- meilleur TRG: environ après 70 mois - individuels RCi, taux RCs, RC, TBRP: approximativement après 30 et 70 mois - SSP: approximativement après 30 et 70 mois - SG: approximativement après 30 et 70 mois - La tolérance globale de l'association de PAN, BTZ et Dex: approximativement après 30 et 70 mois - Pharmacocinétiques: approximativement après 30 mois - Exposition-réponse: approximativement après 30 mois - TAP, TR, DR: approximativement après 30 et 70 mois - HRQoL: approximativement après 30 et 70 mois |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 63 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Brazil |
Canada |
Korea, Republic of |
Lebanon |
Thailand |
United States |
France |
Poland |
Sweden |
Netherlands |
Spain |
Czechia |
Germany |
Greece |
Italy |
Belgium |
Hungary |
Norway |
Portugal |
Russian Federation |
Turkey |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
LVLS |
Dernière visite du dernier patient |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 6 |