E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Multiple myeloma |
Mieloma multiplo |
|
E.1.1.1 | Medical condition in easily understood language |
Multiple myeloma |
Mieloma multiplo |
|
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 | 17.0 |
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 compare the efficacy of daratumumab when combined with VELCADE and dexamethasone (DVd) to that of VELCADE and dexamethasone (Vd), in terms of progression-free survival (PFS) in subjects with relapsed or refractory multiple myeloma. |
Consiste nel confrontare l'efficacia di daratumumab in combinazione con VELCADE (bortezomib) e desametasone (DVd) rispetto a quella di VELCADE e desametasone (Vd), in termini di sopravvivenza senza progressione (PFS), in soggetti con mieloma multiplo recidivante o refrattario. |
|
E.2.2 | Secondary objectives of the trial |
The major secondary objectives are as follows:
- To evaluate clinical outcomes including time to disease progression (TTP), overall response rate (ORR), and overall survival (OS).
- To evaluate the proportion of subjects with a response of very good partial response (VGPR) or better.
- To evaluate duration of and time to response.
- To assess the safety and tolerability of daratumumab when administered in combination with Vd.
- To assess Minimal Residual Disease (MRD) in subjects who achieve ≥VGPR.
- To assess the pharmacokinetics of daratumumab in combination with Vd.
- To assess the immunogenicity of daratumumab.
- To evaluate treatment effects on patient reported outcomes (PROs) including the EuroQol-5 Dimensions (EQ-5D-5L) and EORTC QLQ-C30.
- To evaluate clinical efficacy of DVd in high risk molecular subgroups (del17p, t(4;14), t(14;20), UAMS-70). |
Gli obiettivi secondri principali sono:
•Valutare i risultati clinici tra cui tempo prima della progressione della malattia (TTP), tasso di risposta generale (ORR) e sopravvivenza globale (OS).
•Valutare la proporzione dei soggetti con risposta parziale molto buona (VGPR) o migliore.
•Valutare la durata della risposta e il tempo trascorso prima della risposta.
•Determinare la sicurezza e la tollerabilità di daratumumab somministrato in combinazione con Vd.
•Valutare la malattia residua minima (MRD) in soggetti che raggiungono >VGPR.
•Valutare la farmacocinetica di daratumumab in combinazione con Vd.
• Valutare l'immunogenicità di daratumumab.
•Valutare gli effetti del trattamento sugli esiti riferiti dai pazienti (PRO) tra cui dimensioni EuroQol-5 (EQ-5D-5L) e EORTC QLQ-C30.
•Valutare l'efficacia clinica di DVd nei sottogruppi molecolari a rischio elevato (del17p, t(4;14), t(14;20),UAMS-70).
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Must have documented multiple myeloma
- Must have received at least 1 prior line of therapy for multiple myeloma
- Must have documented evidence of progressive disease as defined by the
International Myeloma Working Group criteria on or after their last regimen
- Must have an Eastern Cooperative Oncology Group Performance Status score of 0, 1, or 2
- Must have achieved a response (partial response or better) to at least 1 prior regimen |
-Presentare un mieloma multiplo documentato
-Aver ricevuto almeno una precedente linea terapeutica per il mieloma multiplo
-Mostrare una evidenza documentata di progressione di malattia definita in base ai criteri IMWG durante o dopo l'ultimo regime
-Presentare un punteggio dello stato di performance ECOG pari a 0, 1 o 2
-Avere raggiunto una risposta (risposta parziale o migliore) almeno ad un precedente regime |
|
E.4 | Principal exclusion criteria |
- Has received daratumumab or other anti-CD38 therapies previously
- Is refractory to VELCADE (had progression of disease while receiving VELCADE therapy or within 60 days of ending VELCADE therapy
- Is intolerant to VELCADE (ie, discontinued due to any adverse event while on VELCADE treatment)
- Has received anti-myeloma treatment within 2 weeks or 5 pharmacokinetic half-lives of the treatment, whichever is longer, before the date of randomization
- Has a history of malignancy (other than multiple myeloma) within 3 years before the date of randomization
- Has any concurrent medical condition or disease (eg, active systemic infection) that is likely to interfere with study procedures |
-Il soggetto ha ricevuto precedenti terapie con daratumumab o altre terapie anti-CD38.
-Il soggetto è refrattario a VELCADE (cioè il soggetto ha manifestato una progressione della malattia durante la terapia con VELCADE o entro 60 giorni dal termine della terapia con VELCADE).
-Il soggetto è intollerante a VELCADE (cioè ne ha interrotto l'assunzione a causa di eventi avversi manifestatisi durante il trattamento con
VELCADE).
-Il soggetto ha ricevuto un trattamento anti-mieloma entro 2 settimane o 5 emivite farmacocinetiche dal trattamento, a seconda del periodo più lungo, prima della data della randomizzazione.
-Il soggetto ha una storia di tumore maligno (diverso dal mieloma multiplo) sviluppato nei 3 anni precedenti la data di randomizzazione 8. Il soggetto presenta un coinvolgimento meningeo noto del mieloma multiplo.
-Il soggetto presenta una condizione o patologia medica concomitante (ad es., infezione sistemica attiva) che può interferire con le procedure |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of participants with progression-free survival (PFS) |
Percentuale di partecipanti senza progressione di malattia (PFS)
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline, up to the end of the study |
Dalla visita di baseline fino alla fine dello studio |
|
E.5.2 | Secondary end point(s) |
1. Time to disease progression (TTP)
2. Percentage of Participants With Overall Response
3. Duration of response
4. Time to Response
5. Percentage of participants with a very good partial response (VGPR) or better
6. Percentage of participants with Minimal Residual Disease (MRD)
7. Percentage of participants with overall survival (OS) |
1. Tempo alla progressione di malattia (TTP)
2. Percentuale di partecipanti con risposta
3. Durata della risposta
4. Tempo alla risposta
5. Percentuale di partecipanti con una risposta veramente buona (VGPR) o migliore
6. Percentuale di partecipanti con malattia minima residua (MRD)
7. Percentuale di partecipanti in sopravvivenza (OS) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
- For all secondary end points except 4 is Baseline, up to the end of the study
- for secondary end point 4 is Baseline until first documented response |
-Per tutti gli end-points secondari eccetto il nr. 4 è dalla visita di baseline fino alla fine dello studio
-Per end-point secondario nr. 4 è dalla visita di baseline fino alla prima risposta documentata |
|
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 | No |
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 | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 14 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 78 |
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 |
Czech Republic |
Germany |
Hungary |
Italy |
Korea, Republic of |
Mexico |
Netherlands |
Poland |
Russian Federation |
Spain |
Sweden |
Turkey |
Ukraine |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
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
|
the following is included in the protocol : The study is considered completed after 320 deaths have occurred. |
definizione in protocollo: lo studio è considerato completo al raggiungimento di 320 decessi |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 27 |