E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Myelofibrosis (MF) is classified as a myeloproliferative neoplasm (MPN) |
Mielofibrosi (MF) classificata come neoplasia mieloproliferativa (MPN) |
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E.1.1.1 | Medical condition in easily understood language |
Myelofibrosis |
Mielofibrosi |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028537 |
E.1.2 | Term | Myelofibrosis |
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 primary objectives of this study are to evaluate spleen response rate and symptom response rate of 2 dose regimens of imetelstat (9.4 mg/kg and 4.7 mg/kg imetelstat given intravenous [IV] every 3 weeks) in subjects with intermediate-2 or high-risk MF who are relapsed after or refractory to JAK inhibitor treatment. |
Gli obiettivi primari di questo studio sono la valutazione del tasso di risposta della milza e del tasso di risposta dei sintomi a 2 regimi di dosaggio di Imetelstat (9,4 mg/kg e 4,7 mg/kg di Imetelstat somministrati per via endovenosa [IV] ogni 3 settimane) in soggetti con mielofibrosi (MF) a rischio intermedio-2 o alto, recidivi o refrattari al trattamento con inibitore di JAK. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are: - To assess the safety of imetelstat - To assess CR or PR, CI, spleen response, symptoms response, and anemia response per modified 2013 IWG-MRT criteria, duration of responses, and overall survival (OS). - To evaluate the pharmacokinetics of imetelstat - To evaluate the PK/response and pharmacodynamic (PD) relationships with factors that include hemoglobin concentration, spleen size, and platelet count - To evaluate the immunogenicity of imetelstat - To assess the effect of treatment on PROs (patient-reported outcomes) |
Gli obiettivi secondari consistono nel: determinare la sicurezza di Imetelstat; determinare remissione completa (CR) o remissione parziale (PR), miglioramento clinico (CI), risposta della milza, risposta dei sintomi e risposta dell'anemia secondo i criteri dell’International Working Group – Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) modificati nel 2013, durata delle risposte e sopravvivenza generale (OS); valutare la farmacocinetica (PK) di Imetelstat; valutare il rapporto tra la PK/risposta e la farmacodinamica (PD) con i fattori tra cui la concentrazione di emoglobina, le dimensioni della milza e la conta piastrinica; valutare l'immunogenicità di Imetelstat; determinare l'effetto del trattamento in base ai risultati riportati dal paziente (PRO). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Diagnosis of PMF according to the revised WHO criteria; or PET-MF or PPV-MF according to the IWG-MRT criteria - DIPSS intermediate-2 or high risk MF - Measurable splenomegaly prior to study entry as demonstrated by palpable spleen measuring greater than or equal to (>=) 5 cm below the left costal margin OR spleen volume of >= 450 cm^3 measured by MRI
- Active symptoms of MF as demonstrated by a symptom score of at least5 points (on a 0 to 10 scale) on at least one of the symptoms or a score of 3 or greater on at least 2 of the symptoms - Documented progressive disease during or after JAK inhibitor therapy
- ECOG performance status 0, 1 or 2
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-Diagnosi di mielofibrosi primaria (PMF) sulla base dei criteri WHO revisionati o PET-MF o PPV-MF sulla base dei criteri IWG-MRT
-Rischio di MF intermedio-2 o alto secondo il sistema DIPSS
- Splenomegalia misurabile antecedente all'ingresso nello studio, dimostrata da:
• Milza al di sotto del margine costale sinistro (>= a 5cm) alla palpazione
OPPURE
• volume della milza ≥ 450 cm3 misurato tramite risonanza magnetica (RMN)
-Sintomi attivi di MF dimostrati da un punteggio in base ai sintomi di almeno 5 punti (su una scala da 0 a 10) per almeno uno dei sintomi, oppure pari a, o superiore, 3 per almeno 2 dei sintomi
-Progressione di malattia documentata durante o dopo la terapia con l'inibitore di JAK
-Performance status ECOG pari a 0, 1 o 2
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E.4 | Principal exclusion criteria |
Peripheral blood blast count of >= 10% or bone marrow blast count of >=10% - Prior treatment with imetelstat - Major surgery within 4 weeks of randomization - Past or present active hepatitis infection of any type or known acute or chronic liver disease including cirrhosis - Prior history of hematopoietic stem cell transplant |
-Conta di blasti nel sangue periferico ≥10% oppure conta di blasti nel midollo osseo >=10%.
-Precedente trattamento con Imetelstat.
-Intervento chirurgico importante nelle 4 settimane precedenti la randomizzazione.
-Infezione da epatite di qualsiasi tipo passata o in atto o di epatopatia acuta o cronica conosciuta, inclusa la cirrosi.
-Eventuale storia precedente di trapianto di cellule staminali ematopoietiche. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Percentage of participants who Achieve Greater than or equal to 35 percent (%) Reduction in Spleen Volume at Week 24 (Spleen response rate is defined as the percentage of participants who achieve >= 35% reduction in spleen volume at Week 24 from baseline as measured by imaging scans.) - Percentage of participants who Achieve Greater than or equal to 50 percent (%) Reduction in Total Symptom Score at Week 24 (Symptom response rate is defined as the percentage of participants who achieve >= 50% reduction in TSS at Week 24 from baseline as measured by the modified Myelofibrosis Symptom Assessment Form (MFSAF) version 2.0 diary.) |
Percentuale dei partecipanti che raggiungono la riduzione del volume dalle milza alla settimana 24 maggiore o uguale al 35% (il tasso di risposta della milza e definito come la percentuale dei partecipanti che raggiungono la riduzione del volume dalle milza alla settimana 24 maggiore o uguale al 35% dal basale mediante imaging)
Percentuale dei partecipanti che raggiungono la riduzione del punteggio complessivo dei sintomi ≥50%, alla settimana 24 (il tasso di risposta dei sintomi è definite come Percentuale dei partecipanti che raggiungono la riduzione del punteggio complessivo dei sintomi ≥50%, alla settimana 24 dal basale , misurato secondo il diario Myelofibrosis Symptom Assessment Form (MFSAF) v2.0)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
both at 24 weeks |
entrambi a 24 settimane |
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E.5.2 | Secondary end point(s) |
- Complete remission (CR) or partial remission (PR) per modified 2013 IWG-MRT criteria - Clinical improvement (CI) per modified 2013 IWG-MRT criteria - Number of Participants with Responses per 2013 IWG-MRT (Spleen response, symptoms response, and anemia response per modified 2013 IWG-MRT will be assessed.) - Duration of Treatment Response and Remission (Duration of spleen response, duration of symptoms response, duration of CR or PR, duration of CI, and duration of anemia response will be reported.) - Overall Survival (Overall survival is defined as the time from randomization to date of death from any cause.) - European Organization for Research and treatment of Cancer (EORTC) QLQ-C30 Score - EuroQol-EQ-5D (EQ-5D-5L) Health Questionnaire Score - Brief Pain Inventory- Short Form (BPI) Score - Patient's Global Impression of Change (PGIC) - Number of Participants with Adverse Events (AEs) - Maximum Plasma Concentration (Cmax) of Imetelstat (The Cmax is the maximum observed plasma concentration.) - Time to Reach Maximum Concentration (tmax) of Imetelstat (The tmax is time to reach the maximum observed plasma concentration.) - Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC [0-24h]) of Imetelstat (AUC 0-24h is area under the plasma concentration-time curve from time 0 to 24 hours postdose. - Elimination Half-Life (t [1/2] Lambda) of Imetelstat (Elimination halflife (t [1/2] Lambda) is associated with the terminal slope (lambda [z]) of the semi logarithmic drug concentration-time curve, calculated as 0.693/lambda(z).) |
-Remissione completa o remissione parziale per criteri IWG-MRT modificati 2013 - Miglioramento clinico (CI) come da criteri 2013 IWG-MRT -Numero di partecipanti con risposta come da 2013 IWG-MRT modificati (saranno valutati la risposta della milza, la risposta dei sintomi, la risposta di anemia come da criteri 2013 IWG-MRT modificati) -Durata della risposta al trattamento e remissione (saranno riportati la durata della risposta della milza, dei sintomi, CR o PR, CI, anemia) - Sopravvivenza complessiva (definita come tempo dalla randomizzazione al decesso per qualsiasi causa) -Punteggio come da European Organization for Research and treatment of Cancer (EORTC) QLQ-C30 -Punteggio come da EuroQol-EQ-5D (EQ-5D-5L) Health Questionnaire -Punteggio come da Brief Pain Inventory- Short Form (BPI) -Valutazione come da Patient's Global Impression of Change (PGIC) -Numero dei partecipanti con EA -Concentrazione plasmatica massima (Cmax) di Imetestat -Tempo per raggiungere Cmax di Imetelstat -Area sotto la curva concentrazione plasmatica/tempo da tempo 0 a 24 ore (AUC[0-24H]) di Imetelstat -Emivita (t[1/2] Lambda) di Imetelstat
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Up to 3 years |
Fino a 3 anni |
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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 | 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 Biomarker Patient Reported Outcome |
Immunogenicità Biomarcatori Patient Reported Outcome |
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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) | 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 | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
GRUPPI PARALLELI |
PARALLEL GROUPS |
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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 | 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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 47 |
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 |
Belgium |
Canada |
France |
Germany |
Israel |
Italy |
Korea, Democratic People's Republic of |
Spain |
Switzerland |
Taiwan |
United Kingdom |
United States |
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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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The study is considered completed 18 months after the last subject is
enrolled or anytime the sponsor terminates the study, whichever comes
first. |
Lo studio è considerato concluso 18 mesi dopo l'arruolamento dell'ultimo soggetto o qualora lo Sponsor decidesse di chiudere lo studio a seconda dell'evento che si verifica per primo |
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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 | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 8 |
E.8.9.2 | In all countries concerned by the trial days | 9 |