E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Multiple Myeloma |
Mieloma Multiplo |
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E.1.1.1 | Medical condition in easily understood language |
Multiple Myeloma |
Mieloma Multiplo |
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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 | 15.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028228 |
E.1.2 | Term | Multiple myeloma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The objective of this study is to explore the effect of optimized retreatment with bortezomib in combination with dexamethasone followed by prolonged therapy with bortezomib, versus standard retreatment with bortezomib in combination with dexamethasone on PFS |
L'obiettivo primario è quello di valutare l'effetto del ritrattamento ottimizzato con bortezomib in combinazione con desametasone seguito da terapia prolungata con bortezomib rispetto al ritrattamento standard con bortezomib in combinazione con desametasone sulla sopravvivenza libera da progressione (PFS) |
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E.2.2 | Secondary objectives of the trial |
1)Overall response rate (ORR).2)Time to progression (TTP).3)Duration of response (DOR).4)Time to next myeloma therapy (TTNT).5)Overall Survival (OS).6)Eastern Cooperative Oncology Group (ECOG) Performance Status .7)Quality of life (QoL: European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–C30 [EORTC QLQ-C30] and European Quality of Life-5 Dimensions Questionnaire [EQ-5D]).8)Safety |
1)Tasso di risposta global(ORR).2)Tempo alla progressione (TTP).3)Durata della risposta (DOR).4)Tempo alla terapia successiva per il mieloma (TTNT).5)Sopravvivenza globale (OS).6)Performance status secondo la scala ECOG (Eastern Cooperative Oncology Group).7)Qualità della vita (Questionari: QoL: European Organization for Research and treatment of Cancer Quality of Life Questionnaire-C30 [EORTC QLQ-C30] ; and European Quality of Life-5 Dimensions Questionnaire [EQ-5D]).8)Sicurezza |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Have received a bortezomib containing regimen in one of the previous line(s) of therapy and have shown at least PR to the previous bortezomib therapy.Have relapsed / progressed multiple myeloma following 1 or 2 previous lines of therapy as defined in the protocol. Have measurable secretory multiple myeloma: measurable disease for secretory multiple myeloma is defined by at least one of the following measurements: serum M protein greater than or equal to 1 g/dL (≥ 10g/L], urine M-protein of ≥200 mg/24 hours.Have an ECOG performance status of ≤2. Have a life expectancy estimated at screening of ≥6 months. Have a life expectancy estimated at screening of ≥6 months. |
Aver ricevuto un regime terapeutico contenente bortezomib in una delle precedenti linee di terapia ed aver mostrato almeno una PR alla precedente terapia con bortezomib.Presentare recidiva / progressione del mieloma multiplo successivamente a 1 o 2 precedenti linee di terapia come definito nel protocollo.Essere affetto da mieloma multiplo secernente misurabile: la malattia misurabile per il mieloma multiplo secernente è definita da almeno una delle seguenti misurazioni: proteina M nel sangue maggiore o uguale a 1 g/dl (≥10g/l), proteina M nelle urine ≥ 200 mg/24 ore.Avere un performance status secondo la scala ECOG ≤2. Avere una aspettativa di vita stimata allo screening ≥6 mesi. |
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E.4 | Principal exclusion criteria |
Has received more than 2 previous lines of therapy for multiple myeloma or has received no previous bortezomib-containing regimen. Has been refractory to bortezomib, defined as either having progressed during bortezomib therapy or relapsed/progressed within 6 months after the last dose of bortezomib. Has oligosecretory or nonsecretory multiple myeloma. Has a history of a myocardial infarction within 6 months of enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Has peripheral neuropathy or neuropathic pain of grade 2 or greater intensity, as defined by the National Cancer Institute Common Terminology Criteria of Adverse Events (NCI CTCAE), version 4.0. |
Ha ricevuto più di 2 precedenti linee di terapia per il mieloma multiplo o non ha ricevuto alcun regime terapeutico precedente contenente bortezomib. È risultato refrattario a bortezomib, (cioè ha manifestato progressione di malattia durante la terapia con bortezomib o ha manifestato recidiva/progressione entro 6 mesi successivi all'ultima dose somministrata di bortezomib). E’ affetto da mieloma multiplo oligo-secretorio o non secretorio. Presenta una storia di infarto del miocardio entro 6 mesi dall'arruolamento o insufficienza cardiaca di classe III o IV secondo la classificazione NYHA (New York Heart Association), angina non controllata, gravi aritmie ventricolari non controllate o evidenza elettrocardiografica di ischemia acuta o di anomalie attive del sistema di conduzione del cuore. Presenta neuropatia periferica o dolore neuropatico di grado 2 o superiore, come definito dai criteri comuni di terminologia per gli eventi avversi del National Cancer Institute (NCI CTCAE), versione 4.0. |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Once 186 events occured |
una volta verificatisi 186 eventi |
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E.5.2 | Secondary end point(s) |
- ORR - TTP - DOR - TTNT - OS - Changes in ECOG performance status from baseline, and QoL |
- Tasso di risposta global (ORR) - Tempo alla progressione (TTP) - Durata della risposta (DOR) - Tempo alla terapia successiva per il mieloma (TTNT) - sopravvivenza globale (OS) _Variazioni dell'ECOG dal basale, e qualità della vita |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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 | 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) | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
braccio osservazionale |
Observational arm |
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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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 57 |
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 |
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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
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3 years after the 186 events occured |
3 anni dopo 186 eventi occorsi |
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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 | 7 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 |