E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Multiple myeloma |
Mieloma Múltiple |
|
E.1.1.1 | Medical condition in easily understood language |
Multiple myeloma |
Mieloma Múltiple |
|
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. |
El objetivo principal es comparar la eficacia de daratumumab combinado con VELCADE (bortezomib) y dexametasona (DVd) con la de VELCADE y dexametasona (Vd) en la supervivencia libre de progresión (SSP) en sujetos con mieloma múltiple en recaída o refractario al tratamiento. |
|
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). |
? Evaluar los criterios de valoración clínicos, incluidos el tiempo hasta la progresión de la enfermedad (TPE), la tasa de respuesta global (TRG) y la supervivencia global (SG).
? Evaluar la proporción de sujetos con una respuesta parcial muy buena (RPMB) o mejor.
? Evaluar la duración de la respuesta y el tiempo hasta la respuesta.
? Evaluar la seguridad y la tolerabilidad de daratumumab cuando se administra combinado con Vd.
? Evaluar la enfermedad residual mínima (ERM) en sujetos que logren una respuesta ? RPMB.
? Evaluar la farmacocinética de daratumumab en combinación con Vd.
? Evaluar la inmunogenicidad de daratumumab.
? Evaluar los efectos del tratamiento en los resultados comunicados por el paciente (RCP), incluidas las puntuaciones obtenidas en los cuestionarios EuroQol-5 Dimensiones (EQ-5D-5L) y EORTC QLQ-C30.
? Evaluar la eficacia clínica de DVd en subgrupos moleculares de alto riesgo (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 |
- El sujeto deberá tener mieloma múltiple comprobado,
- El sujeto deberá haber recibido al menos una línea previa de tratamiento para el mieloma múltiple
- El sujeto deberá tener pruebas documentadas de progresión de la enfermedad (PE), definida por los criterios del IMWG, en o después del último régimen.
- El sujeto deberá tener una puntuación del estado funcional del ECOG de 0, 1 ó 2.
- El sujeto deberá haber conseguido una respuesta (respuesta parcial [RP] o mejor) al menos a un régimen previo |
|
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 |
- El sujeto ha recibido previamente daratumumab u otros tratamientos anti-CD38.
- El sujeto no responde a VELCADE (es decir, el sujeto presenta progresión de la enfermedad durante el tratamiento con VELCADE o en los 60 días siguientes a la finalización del tratamiento con VELCADE).
- El sujeto es intolerante a VELCADE (es decir, ha tenido que suspender la medicación por algún acontecimiento adverso aparecido durante el tratamiento con VELCADE).
- El sujeto ha recibido tratamiento contra el mieloma en las dos semanas o cinco semividas farmacocinéticas del tratamiento previas a la fecha de aleatorización, lo que sea más largo.
- El sujeto tiene antecedentes de neoplasia maligna (distinta del mieloma múltiple) en los tres años previos a la fecha de aleatorización.
- El sujeto sufre cualquier proceso médico o enfermedad concurrente (p. ej., infección sistémica activa) que es probable que interfiera en los procedimientos del estudio. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of participants with progression-free survival (PFS) |
Porcentaje de participantes con supervivencia libre de progresión (SLP) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline, up to the end of the study |
Visita basal, hasta el final del estudio |
|
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. Tiempo hasta la progresión de la enfermedad
2. Tasa de respuesta global.
3. Duración de la respuesta.
4. Tiempo hasta la respuesta.
5. Proporción de participantes con respuesta parcial muy buena (RPMB) o mejor.
6. Proporción de participantes con enfermedad mínima residual (EMR).
7. Proporción de sujetos con supervivencia global (SG) |
|
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 |
- Para todos los objetivos secundarios excepto el 4, desde la visita basal hasta el fin del estudio.
- Para el objetivo secundario 4 desde la visita basal hasta la primera respuesta documentada |
|
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 | 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 | No |
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 | 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 | 7 |
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. |
|
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 | 2 |
E.8.9.1 | In the Member State concerned days | 27 |
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 |