E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Lymphoid or myeloid neoplasm with 8p11 rearrangement known to lead to FGFR1 activation |
Neoplasia linfoide o mieloide con riarrangiamento 8p11 noto per portare all¿attivazione di FGFR1 |
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E.1.1.1 | Medical condition in easily understood language |
Lymphoid or myeloid neoplasm with 8p11 rearrangement |
Tumore linfoide o mieloide con riarrangiamento 8p11 |
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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 | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10072680 |
E.1.2 | Term | Fibroblast growth factor 23 increased |
E.1.2 | System Organ Class | 10022891 - Investigations |
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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 | 10009714 |
E.1.2 | Term | CNS neoplasia |
E.1.2 | System Organ Class | 100000004864 |
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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 |
The primary objective of this study is to evaluate the efficacy of INCB054828 in subjects with myeloid/lymphoid neoplasms with fibroblast growth factor receptor (FGFR) 1 rearrangement. |
L¿obiettivo principale di questo studio ¿ valutare l¿efficacia di INCB054828 in soggetti affetti da neoplasie mieloidi/linfoidi con riarrangiamento del recettore del fattore di crescita dei fibroblasti (FGFR) 1. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to evaluate the safety of INCB054828 in subjects with myeloid/lymphoid neoplasms with FGFR1 rearrangement. |
L¿obiettivo secondario ¿ valutare la sicurezza di INCB054828 in soggetti affetti da neoplasie mieloidi/linfoidi con riarrangiamento FGFR1. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Men and women, aged 18 or older. • Documented lymphoid or myeloid neoplasm with 8p11 rearrangement known to lead to FGFR1 activation, based on standard diagnostic cytogenetic evaluation performed locally, before signing informed consent for this study. • Only subjects who are not candidates for stem cell transplantation, or have relapsed after stem cell transplantation and delayed lymphocyte infusion and who have progressed and are not candidates for other disease-modifying therapies are eligible for the study. All relapsed/refractory subjects must have evidence of either cytogenetic or hematological disease and have no evidence of residual toxicity (eg, graft-versus-host disease requiring treatment). • Life expectancy = 12 weeks. • ECOG performance status 0 to 2. |
• Uomini o donne di età =18 anni. • Neoplasia mieloide o linfoide con riarrangiamento 8p11, nota per portare all’attivazione di FGFR1, documentata prima di firmare il modulo di consenso informato per questo studio.
• Aspettativa di vita =12 settimane. • Stato di validità ECOG da 0 a 2.
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E.4 | Principal exclusion criteria |
• Prior receipt of a selective FGFR inhibitor. • History and/or current evidence of ectopic mineralization/calcification, including but not limited to soft tissue, kidneys, intestine, myocardia, or lung, except calcified lymph nodes and asymptomatic arterial or cartilage/tendon calcifications. • Current evidence of corneal disorder/keratopathy, including but not limited to bullous/band keratopathy, corneal abrasion, inflammation/ulceration, and keratoconjunctivitis, as confirmed by ophthalmologic examination. • Use of any potent cytochrome P450 3A4 inhibitors or inducers within 14 days or 5 half-lives (whichever is shorter) before the first dose of study drug. |
• Trattamento pregresso con un inibitore selettivo di FGFR. • Anamnesi e/o evidenza corrente di mineralizzazione/calcificazione ectopica, comprese a titolo esemplificativo ma non esaustivo quelle a livello di tessuto molle, reni, intestino, miocardio o polmoni, eccetto linfonodi calcificati e calcificazioni asintomatiche a livello di arterie o di cartilagine/tendine. • Evidenza corrente di disturbo corneale/cheratopatia, comprese a titolo esemplificativo ma non esaustivo cheratopatia bollosa/a banda, abrasione corneale, infiammazione/ulcera e cheratocongiuntivite, come confermato da esame oftalmologico. • Uso di qualsiasi inibitore o induttore potente del citocromo P450 3A4 nei 14 giorni o nelle 5 emivite (qualsiasi sia il periodo più breve) che precedono la prima dose del farmaco dello studio.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this study is the proportion of subjects who achieve CR as determined by investigator assessment according to the response criteria listed in Appendix D of the protocol |
L’endpoint primario di questo studio è la percentuale di soggetti che raggiungono una risposta completa (CR), determinata dalla valutazione dello sperimentatore secondo i criteri relativi alla risposta elencati nell'Appendice D del protocollo. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Bone marrow biopsies or aspirates will be obtained before randomization and then every 3 cycles starting from Cycle 2 Day 1. After the first 12 months of treatment, a bone marrow biopsy or aspirate will be obtained every 6 cycles for subjects who have not yet achieved complete cytogenic response (CCyR) or every 12 cycles if the subject has a confirmed CCyR until Month 24. Following Month 24, a bone marrow biopsy or aspirate will be obtained every 12 months until disease progression or end of treatment. |
Prima della randomizzazione e poi ogni 3 cicli a partire dal giorno 1 del ciclo 2 saranno prelevati campioni bioptici o di agoaspirato di midollo osseo. Dopo i primi 12 mesi di trattamento sarà eseguita la biopsia o l’agoaspirato del midollo osseo ogni 6 cicli per i soggetti che non hanno ancora raggiunto una risposta citogenica completa (CCyR) o ogni 12 cicli se i soggetti presentano una CCyR confermata, fino al mese 24. Dopo il mese 24 sarà eseguito il prelievo di un campione bioptico o di agoaspirato di midollo osseo ogni 12 mesi fino a progressione della malattia o conclusione del trattamento. |
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E.5.2 | Secondary end point(s) |
• The proportion of subjects who achieve response, defined as a best response of CR or PR, as determined by investigator assessment according to the response criteria listed in Appendix D of the protocol. • The proportion of subjects who achieve a complete cytogenetic response (CCyR) as assessed by local analysis and investigator evaluation. • The proportion of subjects who achieve a partial cytogenetic response (PCyR) as assessed by local analysis and investigator evaluation. • Duration of CR, defined as the time from first assessment of CR to the earlier of disease progression or death due to any cause. • Duration of response, defined as the time from first assessment of CR or PR to the earlier of disease progression or death due to any cause. - Progression-free survival. - Overall survival. - Safety and tolerability, as assessed by evaluating the frequency, duration, and severity of adverse events; through review of findings of physical examinations, changes in vital signs, and electrocardiograms (ECGs); and through clinical laboratory blood and urine sample evaluations. |
- percentuale di pazienti che raggiungono una risposta, definita come migliore risposta di CR o risposta parziale (PR), determinata dalla valutazione dello sperimentatore secondo i criteri relativi alla risposta dell'Appendice D del protocollo; • percentuale di pazienti che raggiungono una risposta citogenetica completa (CCyR) determinata dall'analisi locale e dalla valutazione dello sperimentatore; • percentuale di pazienti che raggiungono una risposta citogenetica parziale (PCyR) determinata dall'analisi locale e dalla valutazione dello sperimentatore; • durata della CR, definita come il tempo dalla prima valutazione della CR alla primissima progressione della malattia o morte per ogni causa; • durata della risposta, definita come il tempo dalla prima valutazione della CR o PR alla primissima progressione della malattia o morte per ogni causa - Sopravvivenza libera da progressione. - Sopravvivenza generale. - Sicurezza e tollerabilit¿ valutate in base a frequenza, durata e gravit¿ degli eventi avversi, mediante esame dei riscontri degli esami obiettivi, variazione dei parametri vitali ed elettrocardiogrammi (ECG) e analisi cliniche di laboratorio di campioni ematici e di urina. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Bone marrow biopsies or aspirates (or peripheral blood if the marrow aspiration is a dry tap) will be obtained within 6 weeks before enrollment (Cycle 1 Day 1), after 6 (± 1) weeks on treatment, and then every 9 (± 1) weeks for the first 12 months of treatment. After the first 12 months of treatment, a bone marrow biopsy or aspirate will be obtained every 18 (± 1) weeks for subjects who have not yet achieved complete cytogenetic response (CCyR) or every 36 (± 1) weeks if the subject has a confirmed CCyR until Month 24. Following Month 24, a bone marrow biopsy or aspirate will be obtained every 52 (± 2) weeks until disease progression or EOT. |
I campioni bioptici di midollo osseo o agoaspirato (or sangue periferico se il midollo raccolto è insufficiente) saranno ottenuti entro 6 settimane dall'arruolamento (Ciclo 1 giorno 1), dopo 6 (± 1) settimane dal trattamento, e poi dopo ogni 9 (± 1) settimane dai primi 12 mesi di trattamento. Dopo i primi 12 mesi di trattamento sarà eseguita la biopsia o l'agoaspirato del midollo osseo ogni 18 (± 1) settimane per i soggetti che non hanno ancora raggiunto la risposta citogenica completa (CCyR) o ogni 36 (± 1) settimane se i soggetti presentano una CCyR confermata, fino al mese 24. Dopo il mese 24 sarà eseguito il prelievo di un campione bioptico o di agoaspirato di midollo osseo ogni 52 (± 2) settimane fino a progressione della malattia o conclusione del trattamento. |
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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 | 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) | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 1 |