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 |
Hematological B-cell malignancy characterized by dysregulated proliferation of BM plasma cells. |
Malignità ematologica dei linfociti B caratterizzata da proliferazione disregolata delle plasmacellule BM. |
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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 | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028228 |
E.1.2 | Term | Multiple myeloma |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028228 |
E.1.2 | Term | Multiple myeloma |
E.1.2 | System Organ Class | 100000004864 |
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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 |
To compare the efficacy of elranatamab (Arm A) versus lenalidomide (Arm B) |
Confrontare l’efficacia di elranatamab (Braccio A) con quella di lenalidomide (Braccio B) |
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E.2.2 | Secondary objectives of the trial |
• To compare the efficacy of Arm A vs Arm B • To determine the safety and tolerability of elranatamab • To evaluate the PK of elranatamab • To evaluate the immunogenicity of elranatamab • To evaluate the impact of study intervention on participant healthrelated quality of life (HRQoL) |
- Confrontare l’efficacia del Braccio A con quella del Braccio B - Determinare la sicurezza e tollerabilità di elranatamab - Valutare la PK di elranatamab - Valutare l'immunogenicità di elranatamab - Valutare l’impatto del trattamento dello studio sulla qualità della vita correlata alla salute (HRQoL) dei partecipanti |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Diagnosis of MM as defined according to IMWG criteria (Rajkumar, 2014) History of induction therapy and autologous stem cell transplant. Randomization must occur within 120 days from the stem cell transplant. For participants who receive consolidation therapy after ASCT, randomization must occur within 60 days of consolidation and within 6 months from ASCT. - Partial Response or better according to IMWG criteria at the time of randomization - MRD positive (=10^-5) at screening by central laboratory NGS test (ClonoSEQ assay) Must have an archival bone marrow aspirate sample(s) that identified the dominant malignant (index) clone that is used to track MRD status. This sample should preferably be collected before induction treatment (eg, at diagnosis) or before transplant. - ECOG performance status = 1 - Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade = 1 - Not pregnant and willing to use contraception |
- Precedente diagnosi di MM come definito in base ai criteri IMWG (Rajkumar et al., 2014). Ananmesi di terapia di induzione e di trapianto autologo di cellule staminali. La randomizzazione deve avvenire entro 120 giorni dal trapianto di cellule staminali. Per i partecipanti che ricevono terapia di consolidamento dopo ASCT, la randomizzazione deve avvenire entro 60 giorni dal consolidamento e entro 6 mesi dall'ASCT. - Risposta Parziale (PR) o migliore secondo i criteri IMWG al momento della randomizzazione. - MRD positiva (=10-5) allo screening mediante test NGS del laboratorio centrale (test clonoSEQ® di Adaptive Biotechnologies). - I partecipanti devono disporre di un campione (o campioni) di aspirato di midollo osseo archiviato/i che identifichi(no) il clone maligno dominante (indice) utilizzato per monitorare lo stato della MRD. Questo campione deve essere prelevato preferibilmente prima del trattamento di induzione (ad es., alla diagnosi) o prima del trapianto. - Stato di validità - Elettrocorticografia (ECOG) =1. - Effetti acuti risolti di qualsiasi terapia precedente fino al basale di gravità o grado =1 secondo i Criteri della Terminologia Comune per gli Eventi Avversi (CTCAE). - Partecipante non incinta e disposta ad usare contraccezione. |
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E.4 | Principal exclusion criteria |
- Plasma cell leukemia - POEMS syndrome - Systematic amyloid light chain amyloidosis - Previous MM maintenance treatment - Prior treatment with BCMA targeted therapy - Any other active malignancy within 3 years prior to enrolment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ - Active, uncontrolled bacterial, fungal, or viral infection, including (but not limited to) HBV, HCV, and known HIV or AIDS-related illness - Previous administration with an investigational drug or vaccine within 30 days (or as determined by the local requirement) or 5 half lives preceding the first dose of study intervention used in this study (whichever is longer) |
- Leucemia plasmacellulare - Sindrome POEMS - Amiloidosi sistemica da amiloide a catena leggera - Precedente trattamento di mantenimento per MM - Precedente trattamento con terapia mirata basata sull’Antigene di Maturazione delle Cellule B (BCMA) - Qualsiasi altro tumore maligno attivo nei 3 anni precedenti l’arruolamento, fatta eccezione per il carcinoma cutaneo basocellulare o squamocellulare adeguatamente trattato, o carcinoma in situ. - Partecipanti con infezione batterica, fungina o virale attiva, non controllata, tra cui a titolo esemplificativo: Virus dell’Epatite B (HBV), Virus dell’Epatite C (HCV) e nota malattia correlata all’HIV o all’AIDS. - Precedente somministrazione di un farmaco sperimentale o vaccino 30 giorni (o secondo quanto stabilito dai requisiti locali) oppure 5 emivite prima della prima dose del trattamento dello studio utilizzato nel presente studio (a seconda di quale sia il periodo più lungo). |
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E.5 End points |
E.5.1 | Primary end point(s) |
• MRD negativity rate per IMWG as assessed via NGS • PFS by BICR per IMWG |
- Tasso di negatività della MRD secondo IMWG valutato mediante Sequenziamento Genetico di Nuova Generazione (NGS) - PFS valutata mediante Riesame Centrale Indipendente in Cieco (BICR) secondo IMWG |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
MRD negativity rate - 12 months after randomization per IMWG as assessed via NGS PFS - Assessed approximately every 28 days and for approximately 5 years |
- Tasso di negatività della MRD - 12 mesi dopo la randomizzazione secondo IMWG valutato tramite NGS - PFS - Valutata circa ogni 28 giorni e per circa 5 anni |
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E.5.2 | Secondary end point(s) |
• PFS by investigator per IMWG • Overall MRD negativity rate per IMWG • Duration of MRD negativity per IMWG • Sustained MRD negativity per IMWG • CRR by BICR and investigator per IMWG • DOCR by BICR and investigator per IMWG • OS • AEs and laboratory abnormalities as graded by NCI CTCAE v5.0. • Severity of CRS and ICANS assessed according to ASTCT criteria (Lee et al, 2019). • Pre- and postdose concentrations of elranatamab • ADAs and NAbs against elranatamab • EORTC QLQ-C30+MY20 |
- PFS valutata dallo sperimentatore secondo IMWG - Tasso complessivo di negatività della MRD secondo IMWG - Durata della negatività della MRD secondo IMWG - Negatività sostenuta della MRD secondo IMWG - Tasso di Risposta Completa (CRR) valutato tramite BICR e dallo sperimentatore secondo IMWG - Durata della Risposta Completa (DOCR) valutata tramite BICR e dallo sperimentatore secondo IMWG - Sopravvivenza Globale (OS) - EA e anomalie di laboratorio classificati secondo i Criteri Terminologici Comuni per gli Eventi Avversi (CTCAE) del National Cancer Institute (NCI) v5.0. - Severity of CRS and ICANS assessed according to ASTCT criteria (Lee et al, 2019). - Concentrazioni pre-dose e post-dose di elranatamab - ADA e NAb anti-elranatamab - Questionario sulla Qualità della Vita Core 30 (QLQ-C30) e Mieloma 20 (MY20) dell’EORTC |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• PFS - Assessed approx. every 28 days and for approx. 5 years • MRD negativity rate (Overall, Duration and Sustained) - Assessed every 6 months and for approx. 5 years • CRR & DOCR - Assessed approximately every 28 days and for approx. 5 years • OS - Assessed For approx. 5 years • AEs and laboratory abnormalities - Up to 90 days after last dose for AE frequency and at every cycle (each cycle ~ 28 days) for lab abnormalities • Severity of CRS and ICANS - Assessed at every cycle • Pre- and post-dose concentrations of elranatamab - Assessed approx. every 1 - 3 cycles • ADAs and NAbs against elranatamab - Assessed approx. every 1 to 6 cycles • EORTC QLQ-C30+MY20 - Assessed every cycle for year 1, every 3 cycles for year 2 and then once every 6 cycles |
Per ulteriori dettagli si rimanda al protocollo di studio allegato alla presente. |
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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 | 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 | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity; Biomarkers; Genetic |
Immunogenicità; Biomarkers; Genetica |
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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 | 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) | 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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
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 | Information not present in EudraCT |
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 |
Canada |
India |
Israel |
Japan |
Korea, Republic of |
Russian Federation |
Taiwan |
Turkey |
United States |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
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 | 5 |
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 |