| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| relapsed or refractory multiple myeloma (MM) |
| Mieloma múltiple (MM) recidivante o refractario |
|
| E.1.1.1 | Medical condition in easily understood language |
| (Blood cancer) certain blood cells multiply abnormally in the bone marrow, impair the production of other blood cells and produce proteins that cumulate in other organs impairing their functioning |
| Cáncer de sangre,ciertas células de sangre se multiplican anormalmente en médula,ponen en peligro producción de célula de sangre,producen proteínas acumulándose en órganos impidiendo su funcionamiento |
|
| 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 |
|
| 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 POM + BTZ + LD-DEX with BTZ + LD-DEX in subjects with relapsed or refractory MM |
| Comparar la eficacia de POM + BTZ + BD-DEX frente a BTZ + BD-DEX en sujetos con MM recidivante o refractario |
|
| E.2.2 | Secondary objectives of the trial |
| To evaluate the safety and additional efficacy of POM + BTZ + LD-DEX versus BTZ + LD-DEX in subjects with relapsed or refractory MM. |
| Evaluar la seguridad y eficacia adicional de POM + BTZ + BD-DEX frente a BTZ + BD-DEX en sujetos con MM recidivante o refractario |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Must be >= 18 years
2. Understand and voluntarily sign an informed consent document
3. Adhere to the study visit schedule and other protocol requirements.
4. Diagnosis of multiple myeloma and have measurable disease by serum or urine protein electrophoresis (sPEP or uPEP): sPEP >= 0.5 g/dL or uPEP >= 200 mg/24 hours.
5. At least 1 but no greater than 3 prior anti-myeloma regimens.
6. Documented disease progression during or after their last anti-myeloma therapy.
7. Must have received prior treatment with a lenalidomide-containing regimen for at least 2 consecutive cycles.
8. ECOG 0, 1, or 2.
9. Females of childbearing potential (FCBP) must agree to utilize two reliable forms of contraception simultaneously or practice complete abstinence from heterosexual contact for at least 4 weeks before starting study treatment, while participating in the study (including dose interruptions), and for at least 4 weeks after study treatment discontinuation, and must agree to regular pregnancy testing during this timeframe.
10. Females must agree to abstain from breastfeeding during study participation and 4 weeks after study treatment discontinuation.
11. Males must agree to use a latex or synthetic condom
12. Males must also agree to refrain from donating sperm
13. All subjects must agree to refrain from donating blood
14. All subjects must agree not to share medication. |
1.Tener >= 18 años.
2.comprender y firmar voluntariamente un documento de consentimiento informado
3.Ser capaz de cumplir con el calendario de visitas del estudio y con el resto de los requisitos del protocolo.
4.tener un diagnóstico documentado de mieloma múltiple y tener enfermedad mensurable por electroforesis de proteínas, ya sean séricas o urinarias (EFPS o EFPU): EFPS >= 0,5 g/dl o EFPU >= 200 mg/24 horas.
5.haber recibido al menos 1, pero no más de 3 tratamientos previos antimieloma
6.tener progresión de la enfermedad documentada durante o después de su último tratamiento antimieloma.
7.Todos los sujetos deben haber recibido un tratamiento anterior con lenalidomida durante al menos 2 ciclos consecutivos.
8.ECOG de 0, 1 o 2.
9.Las mujeres potencialmente fértiles (MPF) deben acceder a utilizar simultáneamente dos métodos anticonceptivos fiables o a practicar la abstinencia completa de contactos heterosexuales durante al menos 4 semanas antes de iniciar el tratamiento del estudio, durante su participación en el estudio (incluidas las interrupciones de la dosis), y al menos hasta 4 semanas después de la suspensión del tratamiento, y debe acceder a someterse a pruebas de embarazo regulares durante todo este tiempo.
10.Las mujeres deberán estar de acuerdo en no dar el pecho durante su participación en el estudio y al menos durante 4 semanas después de suspender el tratamiento del estudio.
11.Los varones deberán usar obligatoriamente preservativos de látex o sintéticos
12.Los varones deben estar de acuerdo en no donar semen
13.Todos los sujetos también deben estar de acuerdo en no donar sangre
14.Todos los sujetos deben comprometerse a no compartir la medicación. |
|
| E.4 | Principal exclusion criteria |
1. Subjects who had documented progressive disease during therapy or within 60 days of the last dose of a bortezomib-containing therapy under the 1.3 mg/m2 dose twice weekly dosing schedule
2. Peripheral neuropathy Grade 3, Grade 4 or Grade 2 with pain within 14 days prior to randomization
3. Non-secretory multiple myeloma
4. Abnormal lab values (see protocol):
5. Subjects with severe renal impairment (Creatinine Clearance [CrCl] <30 mL/min) requiring dialysis
6. Subjects with prior history of malignancies, other than MM, unless the subject has been free of the disease for >= 5 years with the exception of the following non-invasive malignancies (see protocol)
7. Previous therapy with pomalidomide
8. History of anaphylaxis or hypersensitivity to thalidomide, lenalidomide, bortezomib, boron, mannitol, or dexamethasone
9. >= Grade 3 rash during prior thalidomide or lenalidomide therapy
10. Incidence of gastrointestinal disease that may significantly alter the absorption of pomalidomide
11. Subjects with any one of the following (see protocolo)
12. Subjects who received any of the following within the last 14 days of initiation of study treatment (see protocol)
13. Use of any investigational agents within 28 days or 5 half-lives (whichever is longer) of treatment
See protocol for the rest of exclusion criteria |
1.Sujetos que hayan presentado progresión de la enfermedad documentada durante el tratamiento o en los 60 días de la última dosis de un tratamiento con bortezomib conforme a la pauta de 1,3 mg/m2/dos veces por semana.
2.Neuropatía periférica de grado 3, grado 4 o grado 2 con dolor en los 14 días anteriores a la aleatorización.
3.Mieloma múltiple no secretor.
4.Cualquier anomalía de laboratorio descrita en el protocolo
5.Sujetos con insuficiencia renal severa (aclaramiento de creatinina [ClCr] < 30 mL/min) que requiere diálisis
6.Sujetos con antecedentes de neoplasias malignas, distintas del MM, a menos que el sujeto no haya presentado la enfermedad durante >= 5 años, a excepción de (ver protocolo)
7.Tratamiento anterior con pomalidomida
8.Antecedentes de anafilaxia o hipersensibilidad a la talidomida, lenalidomida, bortezomib, boro, manitol o dexametasona
9.Erupción cutánea >= grado 3 durante un tratamiento anterior con talidomida o lenalidomida
10.Incidencia de enfermedad gastrointestinal que pueda alterar de forma significativa la absorción de la pomalidomida
11.Sujetos que presenten alguno de los siguientes factores (ver protocolo)
12.Sujetos que hayan recibido cualquiera de los siguientes tratamientos en los 14 días anteriores al inicio del tratamiento del estudio (ver protocolo)
13.Uso de cualquier agente en fase de investigación dentro de los 28 días o 5 semividas (el que sea mayor) del tratamiento
Ver protocolo para el resto de criterios de exclusión |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Progression-Free Survival (PFS) |
| Supervivencia Sin Progresión (SSP) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
PFS will be assessed by:
- Bone Marrow Aspiration and/or Biospy ? Screening and as Clinically indicated or to confirm CR
- Quantitative Serum Immunoglobulins, serum-protein electrophoresis (sPEP), 24-hour urine protein electrophoresis, serum and urine immunofixation, serum free light-chain assay, and extramedullary plasmacytoma (EMPs) at Screening and Day 1 of each cycle and PFS Follow-up (if applicable). If EMPs are only assessable radiographically, scans are to be conducted at Screening, C3D1, every 3 cycles thereafter during treatment, at treatment discontinuation, every 63 days (3 cycles) during the PFS follow-up phase, at PFS follow-up phase discontinuation, and when clinically indicated to confirm response (> or = PR)
-Skeletal Surveys ? Screening and when clinically indicated |
-Aspirado o biopsia de MO-Selección y cuando se indique clínicamente o confirme RC
-Niveles de inmunoglobulinas en suero, Electroforesis de proteínas séricas y electroforesis en orina de 24h, Inmunofijación en suero y orina, Análisis de las cadenas ligeras libres en suero y Evaluaciones de los plasmocitomas extramedulares en la selección y D1 de cada ciclo y seguimiento de SSP(si necesario).Si los PEM solo se pueden evaluar radiográficamente,dicha evaluación se llevará a cabo en la selección,el D1C3, cada 3 ciclos a partir de entonces (D1C6, D1C9,etc.) durante y al interrumpir el tratamiento,cada 63 días durantey al interrumpir la fase de seguimiento de la SSP y cuando se indique clínicamente para confirmar la respuesta (? RP).
-serie ósea radiográfica?Selección y cuando se indique |
|
| E.5.2 | Secondary end point(s) |
-Overall Survival (OS)
-Safety (type, frequency, seriousness and severity of AEs, and relationship of AEs to study drug or comparator)
-Overall response rate (ORR) (using the International Myeloma Working Group Uniform [IMWG] response criteria)
-Duration of response |
?Supervivencia global (SG)
?Seguridad (tipo, frecuencia, gravedad e intensidad de los AA, así como la relación de los AA con el fármaco del estudio o el fármaco comparativo)
?Tasa de supervivencia global (TRG) según los criterios de respuesta del Grupo de Trabajo Internacional del Mieloma (IMWG)
?Duración de la respuesta |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
OS: All long-term follow-up phase subjects will be contacted four (4) times a year (every 3 months) to obtain survival status for at least 5 years after the last subject is randomized into the study, or longer if clinically indicated
Safety: i. AEs: After signing ICF and until 28 days after treatment discontinuation; ii. SPM: After signing ICF up to and including the long-term follow-up period and up to 5 years after last subject enrolled
Overall Response Rate (ORR): when assessable
Duration of Response: when assessable |
SG: Se contactará con todos los sujetos incorporados a la fase de seguimiento a largo plazo cuatro (4) veces al año (cada 3 meses) para obtener su estado de supervivencia durante un mínimo de 5 años a partir de la aleatorización del último sujeto en el estudio, o más si está clínicamente indicado.
Seguridad: i. EAs: Después de firmar CI y hasta 28 días después de la discontinuación de tratamiento; ii. SNMP: Después de firmar CI hasta e incluyendo la fase se seguimiento a largo plazo y hasta 5 años a partir de la aleatorización del último sujeto en el estudio
Tasa de respuesta global: cuando sea evaluable
Duración de la respuesta: cuando sea evaluable |
|
| 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 | No |
| 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 100 |
| 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 |
| Austria |
| Belgium |
| Canada |
| Czech Republic |
| Denmark |
| Finland |
| France |
| Germany |
| Greece |
| Hungary |
| Ireland |
| Israel |
| Italy |
| Japan |
| Korea, Republic of |
| Mexico |
| Netherlands |
| Norway |
| Poland |
| Portugal |
| Puerto Rico |
| Slovakia |
| Spain |
| Sweden |
| Switzerland |
| Taiwan |
| Turkey |
| 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 End of Trial is defined as either the date of the last visit of the last subject to complete the study, or the date of receipt of the last data point from the last subject that is required for primary, secondary and/or exploratory analysis, whichever is the later date as pre-specified in the protocol and/or the Statistical Analysis Plan |
| El final del ensayo se define como: - la fecha de la última visita del último sujeto que complete el estudio, o - la fecha de recepción del último punto de datos del último sujeto que se precise para análisis principal, secundario o exploratorio, preestablecida en el protocolo o en el plan de análisis estadístico (PAE), la que sea posterior. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 8 |
| E.8.9.1 | In the Member State concerned months | 4 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 10 |
| 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 |
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