E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic lymphocytic leukemia (CLL) |
Leucemia linfocitica cronica |
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E.1.1.1 | Medical condition in easily understood language |
Chronic lymphocytic leukemia (CLL) |
Leucemia linfocitica cronica |
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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 | PT |
E.1.2 | Classification code | 10008958 |
E.1.2 | Term | Chronic lymphocytic leukaemia |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10029104 |
E.1.2 | Term | Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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 |
-To determine the effect of GS-1101 on the onset, magnitude, and duration of tumor control; -To compare tumor control in subjects receiving rituximab alone in Study GS-US-312-0116 to that observed in the same subjects when receiving the standard dose of GS-1101 alone in Study GS-US- 312-0117; -To assess the effect of GS-1101 on measures of subject well-being, including overall survival (OS), health related quality of life (HRQL), and performance status; -To assess the effects of GS-1101 on disease associated biomarkers and to evaluate potential mechanisms of resistance to GS-1101; -To characterize exposure to GS-1101 as determined by treatment administration and evaluation of GS-1101 plasma concentrations over time; - To describe the safety profile observed with GS-1101; - To estimate health resource utilisation. |
•Determinare l’effetto di GS-1101 sull’esordio, l’entita' e la durata del controllo del tumore; •Confrontare il controllo del tumore nei soggetti che hanno ricevuto solo rituximab nello Studio GS-US-312-0116 rispetto a quello osservato negli stessi soggetti quando ricevono la dose standard di solo GS-1101 nello Studio GS-US-312-0117; •Valutare l’effetto di GS-1101 sugli indicatori del benessere del soggetto, compresa la sopravvivenza globale, la qualita' di vita correlata alla salute e il performance status; •Valutare gli effetti di GS-1101 sui biomarcatori associati alla patologia e valutare i potenziali meccanismi di resistenza a GS-1101; •Caratterizzare l’esposizione a GS-1101 determinata dalla somministrazione del trattamento e dalla valutazione delle conc. plasmatiche di GS-1101 nel tempo; • Descrivere il profilo di sicurezza di GS-1101 •Stimare l’impiego di risorse sanitarie. |
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E.2.2 | Secondary objectives of the trial |
Determining the effect of GS-1101 on the onset, magnitude, and duration of tumor control; overall survival (OS); health-related quality of life (HRQL); changes in subject performance status; disease-associated biomarkers and potential mechanisms of resistance; safety; health resource utilization. |
- Determinare l'effetto di GS-1101 sull’esordio,l’entita' e la durata del controllo del tumore; sopravvivenza globale (OS); qualita' della vita correlata alla salute (HRQL); variazioni del performance status nei pazienti; determinare biomarkers associati alla patologia e potenziali meccanismi di resistenza; sicurezza; impegno delle risorse sanitarie. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Participation in Study GS-US-312-0116; - Occurrence of confirmed, definitive CLL progression while receiving study drug therapy (GS 1101/placebo) in Study GS US 312 0116. Note: Definitive disease progression is CLL progression based on standard criteria and occurring for any reason (ie, increasing lymphadenopathy, organomegaly, or bone marrow involvement; decreasing platelet count, hemoglobin, or neutrophil count; or worsening of disease-related symptoms) other than lymphocytosis. Subjects must have confirmation by the sponsor working in collaboration with an independent review committee (IRC) that the disease has progressed on the clinical trial (Study GS-US-312-0116) before receiving secondary GS 1101 therapy on this extension trial (Study GS-US-312-0117); -Presence of radiographically measurable lymphadenopathy (defined as the presence of ≥1 nodal lesion that measures ≥2.0 cm in the longest dimension [LD] and ≥1.0 cm in the longest perpendicular dimension [LPD] as assessed by CT or MRI); -Permanent cessation of Study GS-US-312-0116 treatment (rituximab and GS-1101/placebo) and no intervening or continuing therapy (including radiotherapy, chemotherapy, immunotherapy, systemic corticosteroids, or investigational therapy) for the treatment of CLL; -The time from permanent cessation of Study GS-US-312-0116 treatment (rituximab and/or GS-1101/placebo) and the initiation of Study GS-US-312-0117 therapy is ≤12 weeks. Note: Study procedures performed as part of Study GS-US-312-0116 need not be repeated and can be used as screening procedures for Study GS-US-312-0117 if performed within 4 weeks prior to initiation of study drug therapy on Study GS-US-312-0117; -Karnofsky performance score of ≥40; -Required baseline laboratory data (within 4 weeks prior to initiation of study treatment). |
-Aver partecipato allo Studio GS-US-312-0116; -Insorgenza di progressione definitiva e confermata della LLC mentre ricevono la terapia con il farmaco dello studio (GS-1101/placebo) nello Studio GS-US-312-0116. Nota: la progressione definitiva della malattia e' la progressione della LLC basata su criteri standard e che insorge per qualsiasi ragione (cioe', linfoadenopatia in aumento, organomegalia o coinvolgimento del midollo osseo; riduzione della conta piastrinica, dell'emoglobina o della conta dei neutrofili; oppure peggioramento dei sintomi correlati alla malattia) diversa dalla linfocitosi. I soggetti devono ricevere la conferma dallo sponsor che opera in collaborazione con un comitato di revisione indipendente (Independent Review Committee, IRC) della progressione della malattia durante la sperimentazione clinica principale (Studio GS-US-312-0116) prima di ricevere la terapia secondaria con GS-1101 in questo studio di estensione (Studio GS-US-312-0117); -La presenza di linfadenopatia misurabile (definita come la presenza di ≥1 lesione nodale della misura di ≥2,0 cm nella dimensione massima [Longest Dimension, LD] e ≥1,0 cm nella massima dimensione perpendicolare [Longest Perpendicular Dimension, LPD] in base a valutazione della tomografia computerizzata [CT ] o della risonanza magnetica [RM]); -Cessazione permanente del trattamento dello Studio GS-US-312-0116 (rituximab e/o GS-1101/placebo) e nessuna terapia intercorrente o proseguita (comprese radioterapia, chemioterapia, immunoterapia, corticosteroidi sistemici o terapia sperimentale) per il trattamento della LLC; -Il periodo di tempo dalla cessazione permanente del trattamento dello Studio GS-US-312-0116 (rituximab e/o GS-1101/placebo) e l’inizio della terapia dello Studio GS-US-312-0117 e' ≤12 settimane. Nota: le procedure di studio eseguite nell’ambito dello Studio GS-US-312-0116 non devono essere ripetute e possono essere utilizzate come procedure di screening per lo Studio GS-US-312-0117 se eseguite entro le 4 settimane precedenti l’inizio della terapia con il farmaco dello Studio GS-US-312-0117; -Punteggio del performance status secondo Karnofsky pari a ≥ 40; -Dati di laboratorio richiesti al basale (entro 4 settimane prima dell’inizio del trattamento dello studio). |
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E.4 | Principal exclusion criteria |
Known histological transformation from CLL to an aggressive lymphoma (ie, Richter transformation); Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of the start of study treatment (Visit 2). Note: Subjects with localized fungal infections of skin or nails are eligible. Subjects may be receiving prophylactic antiviral or antibacterial therapies at the discretion of the investigator; anti-pneumocystis prophylaxis is encouraged; Pregnancy or breastfeeding; Intentional breaking of the blind in Study GS-US-312-0116 by the investigator or the study subject; Concurrent participation in another therapeutic clinical trial; -Prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, electrocardiogram (ECG) finding, or laboratory abnormality that, in the investigator’s opinion, could adversely affect the safety of the subject or impair the assessment of study results. |
Trasformazione istologica nota da LLC in linfoma aggressivo (ovvero, trasformazione di Richter); Evidenza di infezione sistemica batterica, fungina o virale in atto al momento dell’inizio del trattamento dello studio (Visita 2). Nota: i soggetti con infezioni fungine cutanee o ungueali localizzate sono idonei. I soggetti possono ricevere terapie profilattiche antivirali o antibatteriche, a discrezione dello sperimentatore; e' incoraggiata la profilassi anti-Pneumocystis; Gravidanza o allattamento; Violazione intenzionale del cieco nello Studio GS-US-312-0116 da parte dello sperimentatore o del soggetto dello studio; Contemporanea partecipazione ad un’altra sperimentazione clinica terapeutica; Malattia clinicamente significativa pregressa o in atto, condizioni mediche, storia di interventi chirurgici, reperti obiettivi, reperti elettrocardiografici (ECG) o anomalie di laboratorio che, a giudizio dello sperimentatore, potrebbero compromettere la sicurezza del soggetto o la valutazione dei risultati dello studio. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression-free survival (PFS); Overall response rate (ORR); Time to response (TTR); Duration of response (DOR); Time to treatment failure (TTF). |
Determinate la progressione libera da malattia (PFS); Il tasso di risposta globale (ORR); Tempo alla risposta (TTR); Durata della risposta (DOR); Tempo al fallimento del trattamento (TTF). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Every 8-12 weeks. |
Ogni 8-12 settimane. |
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E.5.2 | Secondary end point(s) |
Percent change in lymph node area; Lymph node response rate; Splenomegaly response rate; Hepatomegaly response rate; Platelet response rate; Hemoglobin response rate; Neutrophil response rate. |
Valutare la percentuale di variazione dell'area linfonodale; Tasso di risposta linfonodale; Tasso di risposta splenomegalica; Tasso di risposta epatomegalica; Tasso di risposta piastrinica; Tasso di risposta emoglobinico; Tasso di risposta dei neutrofili. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Every 8-12 weeks. |
Ogni 8-12 settimane. |
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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 | No |
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 | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
- Stesso farmaco ad altro dosaggio |
- same IMP used at different dosage |
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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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
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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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 | 30 |
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 | 30 |
E.8.9.2 | In all countries concerned by the trial days | 0 |