E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed or refractory chronic lymphocytic leukemia (CLL) |
leucemia linfocitica cronica recidivante o refrattaria (LLC) |
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E.1.1.1 | Medical condition in easily understood language |
Relapsed or refractory chronic lymphocytic leukemia (CLL) |
leucemia linfocitica cronica recidivante o refrattaria (LLC) |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008976 |
E.1.2 | Term | Chronic lymphocytic leukemia |
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 overall purpose of the study is to determine if MEDI-551, when used in combination with salvage chemotherapy (bendamustine) in patients with relapsed or refractory CLL who are not eligible for Autologous Stem Cell Transplant (ASCT), has superior efficacy compared to rituximab in the same population. |
L'obiettivo generale dello studio è determinare se MEDI-551, quando usato in combinazione con la chemioterapia di salvataggio (bendamustina) in pazienti affetti da LLC recidiva o refrattaria, che non sono eleggibili per il trapianto autologo di cellule staminali (ASCT), ha una efficacia superiore rispetto a rituximab nella stessa popolazione. |
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E.2.2 | Secondary objectives of the trial |
To assess the safety and tolerability, antitumor activity, overall survival, pharmakokinectics and immunogenicity of MEDI-551 when used in combination with Bendamustine |
Per valutare la sicurezza e la tollerabilità,l'attività antitumorale,la sopravvivenza globale,farmacocinetica e immunogenicità di MEDI-551 quando usato in combinazione con bendamustina |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Histologically confirmed aggressive B-cell Chromic Lymphocytic Leukemia( CLL) according to the National Cancer Institute criteria •Adequate hematological function |
•leucemia linfocitica cronica a cellule B aggressive istologicamente confermata secondo i criteri del National Cancer Institute •adeguata funzionalità ematologica |
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E.4 | Principal exclusion criteria |
• Any chemotherapy, radiotherapy, immunotherapy, biologic, investigational or hormonal therapy for treatment of lymphoma within 42 days prior to treatment • Exposure to Bendamustine within 180 days before study enrollment • Any active secondary malignancy • Prior autologous or allogeneic stem cell transplantation SCT • Clinically significant abnormality on ECG • History of other invasive malignancy within 5 years except for localized/in situ, carcinomas such as cervical carcinoma in situ or basal/squamous skin cancer. • Evidence of active infection • Documented current central nervous system involvement by leukemia or lymphoma |
•Qualsiasi chemioterapia, radioterapia, immunoterapia, biologica, ormonale o terapia sperimentale per il trattamento del linfoma entro 42 giorni prima del trattamento •L'esposizione a bendamustina entro 180 giorni precedenti l'arruolamento dello studio •Qualsiasi tumore maligno secondario attivo •Precedente trapianto SCT allogenico o autologo di cellule staminali •Anomalia dell' ECG clinicamente significativa •Storia di altre neoplasie invasive entro 5 anni, tranne per i carcinomi localizzati/in situ, come il carcinoma cervicale in situ o il cancro della pelle basale/squamoso. •Prove di infezione attiva •Coinvolgimento attuale e documentato del sistema nervoso centrale da leucemia o linfoma |
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E.5 End points |
E.5.1 | Primary end point(s) |
Evaluation of the Overall Response Rate (ORR), including Complete Response (CR) and Partial Response (PR), in adult subjects with relapsed or refractory CLL treated with up to 6 cycles of MEDI-551 in combination with bendamustine versus rituximab in combination with bendamustine. |
Valutazione della ORR, definita come la percentuale di soggetti adulti con LLC recidivante o refrattaria che manifestano una risposta completa o parziale trattati fino a 6 cicli di MED-551 in combinazione con bendamustina rispetto a rituximab in combinazione con bendamustina. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Antitumor activity: Includes Complete Response (CR) rate, Minimal Residual Disease (MRD) negative CR rate, Time to Response (TTR), Time to Progression (TTP), Progression Free Survival (PFS); Overall Survival (OS). Acceptable Dose: Benefit/Risk Analysis of Safety and Efficacy to be determined. Safety and Tolerability: The safety endpoints include Adverse Events (AEs), Serious Adverse Events (SAEs) occurring during the protocol specified reporting period and changes in clinical laboratory evaluations, Electrocardiogram (ECGs), vital signs, and weight from baseline. Immunogenicity (IM): Number and percentage of subjects who develop detectable anti-drug antibodies Pharmacokinetics (PK): Area Under Curve, CMAX, T1-half, Clearance (CL) |
Attività antitumorale: Include il tasso di risposta completa (CR), il tasso di CR negativa senza malattia residua minima (MRD), il tempo alla risposta (TTR), il tempo alla progressione (TTP), la sopravvivenza libera da progressione (PFS) e la sopravvivenza globale (OS). Dose Accettabile: valutazione del rischio/beneficio della sicurezza e dell'efficacia da determinare. Sicurezza e tollerabilità: Gli endpoint di sicurezza includono eventi avversi (EA), eventi avversi seri (SAE) che si verificano durante il periodo specificato dal protocollo e i cambiamenti rispetto al basale nei risultati di laboratorio clinico, negli elettrocardiogrammi (ECG) e nei segni vitali e nel peso. Immunogenicità (IM): Numero e percentuale di soggetti che sviluppano anticorpi anti-farmaco rilevabili. Farmacocinetica (PK): area sotto la curva, CMAX, T1-mezzo, la clearance (CL) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Antitumor activity: Study Day 720 Acceptable dose: Study Day 56 Safety and Tolerability: Study Day 720 IM: Up to Study Day 720 PK: Study Day 1, Study Day 8, Study Day 15, Study Day 22, Study Day 29, Study Day 57, Study Day 85, Study Day 113, Study Day 141, Study Day 169, Study Day 197, Study Day 227, Study Day 255 |
Attività antitumorale: giorno 720 Dose accettabile: giorno 56 Sicurezza e tollerabilità: giorno 720 IM: fino al giorno 720 PK: giorno 1, 8, 15, 22, 29, 57, 85, 113, 141, 169, 197, 227, 255 |
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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 | 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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
E.8.2.3.1 | Comparator description |
rituximab - Stesso farmaco ad altro dosaggio |
rituximab - same IMP used at different dosage |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 16 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 32 |
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 |
Canada |
Israel |
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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The end of the study (''study completion'') is defined as the date of the last protocol-specified visit/assessment (including telephone contact) for the last subject in the study. This date will be after a combined total of 82 deaths occur in the rituximab arm and the selected MEDI-551 arm, or 24 months from the date the last subject is randomized into the study, or the date the sponsor stops the study, whichever occurs first. |
La fine dello studio è definita come la data dell'ultima visita/valutazione specificata dal protocollo(compreso il contatto telefonico) per l'ultimo paziente.Questa data sarà dopo82decessi totali avvenuti in un braccio o 24 mesi dalla LPI. |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 68 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
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 | 68 |