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 | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028228 |
E.1.2 | Term | Multiple myeloma |
E.1.2 | System Organ Class | 100000004864 |
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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 |
The primary objective is to determine if the addition of daratumumab to VMP will prolong PFS compared with VMP. |
El objetivo principal es determinar si la adición de daratumumab a VMP prolonga la supervivencia sin progresión (SSP) en comparación con VMP. |
|
E.2.2 | Secondary objectives of the trial |
- To determine if the addition of daratumumab to VMP will improve clinical outcome as measured by: Time to disease progression (TTP) Stringent CR (sCR) rate CR rate PFS2 (defined as time from randomization to progression on the next line of therapy or death, whichever comes first) Time to next treatment Overall response rate (CR + partial response [PR] rate) Proportion of subjects who achieve very good partial response (VGPR) or better Duration of response Overall survival - To determine the ability of daratumumab to reduce minimal residual disease (MRD) - To assess patient reported outcomes and heath economic/resource utilization - To determine the pharmacokinetics and immunogenicity of daratumumab - To assess the safety and tolerability of daratumumab when administered in combination with VMP - To evaluate clinical efficacy of daratumumab when added to VMP in high risk molecular subgroups. |
-Determinar si la adición de daratumumab a VMP mejora el desenlace clínico en su valoración mediante: Tiempo hasta la progresión de la enfermedad Tasa de respuesta completa estricta Tasa de respuesta completa SSP2 Tiempo hasta el siguiente tratamiento Tasa de respuesta global (tasa de RC+respuesta parcial) % de sujetos que alcancen una respuesta parcial muy buena o mejor Duración de la respuesta Supervivencia global -Determinar la capacidad del daratumumab para reducir la enfermedad residual mínima -Evaluar los resultados comunicados por el paciente y la economía sanitaria/utilización de recursos -Determinar la farmacocinética y la inmunogenia del daratumumab -Evaluar la seguridad y la tolerabilidad del daratumumab administrado en combinación con VMP -Evaluar la eficacia clínica del daratumumab añadido a VMP en subgrupos moleculares de alto riesgo |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Participant with documented multiple myeloma satisfying the CRAB criteria and measurable disease - Participants who are newly diagnosed and not considered candidate for high-dose chemotherapy with stem cell transplantation (SCT) due to: being age >=65 years, or in participants <65 years: presence of important comorbid conditions likely to have a negative impact on tolerability of high dose chemotherapy with stem cell transplantation - Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2 - Meet the clinical laboratory criteria as specified in the protocol - A woman of childbearing potential must have a negative serum pregnancy test at screening within 7 days prior to randomization - Women of childbearing potential must commit to either abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control simultaneously. This includes one highly effective form of contraception (tubal ligation, intrauterine device, hormonal [birth control pills, injections, hormonal patches, vaginal rings or implants] or partner´s vasectomy) and one additional effective contraceptive method (male latex or synthetic condom, diaphragm, or cervical cap). Contraception must begin prior to dosing. Reliable contraception is indicated even where there has been a history of infertility, unless due to hysterectomy or bilateral oophorectomy |
-Con mieloma múltiple documentado que cumpla los criterios CRAB y enfermedad medible ? -Sujeto con diagnóstico reciente y considerado inadecuado para quimioterapia en dosis altas con trasplante de células madre por: Edad >/= 65 años, o en sujetos <65 años: una o varias enfermedades concomitantes importantes que probablemente influyan negativamente en la tolerabilidad de la quimioterapia en dosis altas con trasplante de células madre. -Puntuación del estado funcional del ECOG de 0, 1 o 2 -Resultados de los análisis clínicos antes del tratamiento que cumplan los criterios especificados en el protocolo -Las mujeres potencialmente fértiles deben presentar un resultado negativo en una prueba de embarazo en suero u orina en la selección, en el plazo de los 7 días anteriores la aleatorización. -Las mujeres potencialmente fértiles deben comprometerse a abstenerse en todo momento de mantener relaciones heterosexuales o a utilizar dos métodos anticonceptivos fiables simultáneamente, lo que comprende un anticonceptivo de alta eficacia (ligadura de trompas, dispositivo intrauterino, anticonceptivo hormonal [oral, inyectable, en parches, en anillos vaginales o en implantes] o vasectomía de la pareja) y otro método anticonceptivo eficaz (preservativo masculino de látex o sintético, diafragma o capuchón cervical). La anticoncepción debe comenzar antes del tratamiento. La anticoncepción fiable está indicada incluso con antecedentes de infertilidad, excepto que se deba a histerectomía u ovariectomía bilateral |
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E.4 | Principal exclusion criteria |
- Participant has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, or smoldering multiple myeloma - Participant has a diagnosis of Waldenstrom´s disease, or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions - Participant has prior or current systemic therapy or stem cell transplantation (SCT) for multiple myeloma, with the exception of an emergency use of a short course of corticosteroids before treatment - Participant has peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the national cancer institute common terminology criteria for adverse events (NCI CTCAE) Version 4 - Participant has a history of malignancy (other than multiple myeloma) within 3 years before the date of randomization (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years) - Participant has any concurrent medical or psychiatric condition or disease (example active systemic infection, uncontrolled diabetes, acute diffuse infiltrative pulmonary disease) that is likely to interfere with the study procedures or results, or that in the opinion of the investigator, would constitute a hazard for participating in this study. |
-Sujeto con diagnóstico de amiloidosis primaria, gammapatía monoclonal de significación indeterminada o mieloma múltiple quiescente. -Sujeto con diagnóstico de enfermedad de Waldenström u otros procesos con proteína M de tipo IgM en ausencia de una infiltración de plasmocitos clonales con lesiones óseas líticas. -Sujeto con tratamiento sistémico anterior o actual o trasplante de células madre por mieloma múltiple, excepto la administración de urgencia de un ciclo corto de corticosteroides antes del tratamiento. -Sujeto con neuropatía periférica o dolor neuropático de grado 2 o superior, según la definición de los NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), versión 4. -Sujeto con antecedentes de neoplasia maligna (distinta del mieloma múltiple) en el plazo de los 3 años anteriores a la fecha de la aleatorización (son excepciones el carcinoma cutáneo espinocelular o basocelular y el carcinoma in situ de cuello uterino, así como toda neoplasia maligna que, en opinión del investigador y de acuerdo con el monitor médico del promotor, se considere curada y con un riesgo mínimo de recidiva en un plazo de 3 años). -Sujeto con enfermedad o proceso médico o psiquiátrico concomitante (por ejemplo, infección sistémica activa, diabetes no controlada, neumopatía infiltrativa difusa aguda) que probablemente vaya interferir en los procedimientos o resultados del estudio, o que, en opinión del investigador, suponga un riesgo para la participación en este estudio. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Progression-free Survival (PFS) |
supervivencia sin progresión |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Assess at approximately 41 months from randomization |
Valoración aproximadamente 41 meses desde la aleatorización |
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E.5.2 | Secondary end point(s) |
1. Time to DiseaseProgression (TTP) 2. Percentage of Participants Achieving Stringent Complete Response (sCR) 3. Percentage of Participants Achieving Complete Response (CR) 4. Progression-free Survival on Next Line of Therapy (PFS2) 5. Percentage of Participants With Minimal Residual Disease (MRD) 6. Time to Next Treatment 7. Overall Response Rate (ORR) 8. Percentage of Participants Achieving Very Good Partial Response (VGPR) or Better 9. Duration of Response 10. Overall Survival (OS) |
1.Tiempo hasta la progresión de la enfermedad (THP) 2.Porcentaje de sujetos que alcancen una Respuesta completa estricta (RCe) 3.Porcentaje de sujetos que alcancen una Respuesta completa (RC) 4.Supervivencia sin progresión con la siguiente línea de tratamiento (SSP2) 5.Porcentaje de sujetos con la enfermedad residual mínima (ERM) 6.Tiempo hasta el siguiente tratamiento 7.Tasa de respuesta global (TRG) 8.Porcentaje de sujetos que alcancen una RPMB o mejor 9.Duración de la respuesta 10.Supervivencia global (SG) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- For secondary end points 1-4, 6-9 = Assess at approximately 41 months from randomization - For secondary end points 5 = Week 58, 84, and 110 - For secondary end points 10 = Assess at approximately 41 months after first patient randomized up to a maximum of 5 years after last participant is dosed |
- Para los criterios de valoración secundarios 1-4, 6-9 = Valoración aproximadamente en 41 meses desde la aleatorización - Para el critero secundario de valoración 5 = Semana 58, 84 y 110 - Para el criterio de valoración 10 = Valoración aproximadamente 41 meses desde la aleatorización del primer paciente hasta un máximo de 5 años después de la finalización del último paciente. |
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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 | No |
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 | 129 |
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 |
Argentina |
Australia |
Belgium |
Brazil |
Bulgaria |
Canada |
Croatia |
Czech Republic |
Georgia |
Germany |
Greece |
Hungary |
Italy |
Japan |
Macedonia, the former Yugoslav Republic of |
Poland |
Portugal |
Romania |
Russian Federation |
Serbia |
Spain |
Turkey |
Ukraine |
United Kingdom |
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 end of the study will occur when 330 subjects have died, or 5 years after the last subject is randomized, whichever comes first. |
Lo siguiente está incluido en el protocolo: El fin del estudio tendrá lugar cuando hayan fallecido 330 sujetos, o 5 años después de la aleatorización del último sujeto, lo que suceda antes. |
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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 | 8 |
E.8.9.1 | In the Member State concerned days | 8 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |