E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute Myeloid Leukemia (AML) |
Leucemia Mieloide Acuta |
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E.1.1.1 | Medical condition in easily understood language |
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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 | LLT |
E.1.2 | Classification code | 10000886 |
E.1.2 | Term | Acute myeloid leukemia |
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 |
To determine overall survival (OS) of selinexor as compared to physician´s choice (PC) in patients ≥ 60 years old with relapsed/refractory AML that requires treatment and are ineligible for intensive chemotherapy and/or transplantation. |
Determinare il tempo di sopravvivenza con il trattamento con selinexor, in comparazione con la terapia di scelta del medico, in soggetti >=60 anni con leucemia mieloide acuta recidivata o refrattaria che richiedono trattamento e non sono trattabili con chemioterapia intensiva e/o il trapianto. |
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E.2.2 | Secondary objectives of the trial |
• To determine the proportion of patients whose OS is at least 3 months (OS3.0), • To determine the complete remission rate (CRR), including complete remission with full hematologic recovery (CR), and median disease free survival (DFS) for patients who achieve CR, • To determine the modified CRR (mCRR), including CR or complete remission with incomplete hematologic recovery (CRi) (including complete remission with incomplete platelet recovery (CRp) and median DFS for patients who achieve CR or CRi (including CRp), • To determine the overall response rate (ORR) and duration of overall response (DOR), including CR, CRi, bone marrow CR, and partial remission (PR), • To determine the disease control rate (DCR) defined as ORR + stable disease for ≥ 4 weeks (SD), and duration of DCR, • To assess the safety and tolerability of selinexor (KPT-330), as compared to physician's choice (PC). • Quality of life and patient reported outcomes (FACT-Leukemia, EQ-5D-5L) (QoL)
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determinare a) la % di paz. con sopravvivenza di almeno 3 mesi, b) il tasso di remissione completa (CRR), includendo la remissione completa con recupero completo ematologico (CR), e la media di sopravvivenza libera da malattia (DFS) per i paz. che raggiungono CR, c) il CRR modificato (mCRR), includendo CR o remissione completa con recupero incompleto ematologico (CRi) (includendo la remissione completa con recupero piastrinico incompleto (CRp) e la media di DFS per i paz. che raggiungono CR o CRi (includendo CRp), d) il tasso complessivo di risposta (ORR) e la durata della risposta complessiva (DOR), includendo CR, CRi, midollo osseo CR, e remissione parziale (PR), e) il tasso di controllo della malattia (DCR) definito come ORR + malattia stabile per ≥ 4 settimane (SD), e la durata della DCR, f) la sicurezza e la tollerabilità di selinexor (KPT-330), rispetto a terapia di scelta del medico (PC); g) qualità della vita e outcomes riferiti dai paz. (FACT-leucemia, EQ-5D-5L) (QoL) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients age ≥ 60 years with relapsed/refractory AML (defined using WHO criteria) of any type except for acute promyelocytic leukemia (APL; AML M3), who have poor prognosis (intermediate or adverse risk) cytogenetics, with relapsed or refractory AML, after at least two prior AML therapies (i.e. at least one regimen including cytarabine and at least one regimen including an adequate trial of a hypomethylating agent with at least 2 cycles), who have never undergone, and who are not currently eligible for, stem cell transplantation and are currently deemed unfit for intensive chemotherapy. |
Età >=60 anni; diagnosi di Leucemia Mieloide Acuta (LMA) redicivata/refrattaria secondo i criteri WHO (esclusa la leucemia promielocitica acuta); prognosi citogenetica sfavorevole (rischio intermedio o negativo) in recidiva o refrattarieta dopo almeno 2 terapie anti LMA; non avere mai effettuato e non essere trattabili, nel presente, con trapianto di cellule staminali e/o con chemioterapia intensiva. |
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E.4 | Principal exclusion criteria |
Patients with acute promyelocytic leukemia (AML M3), known central nervous system (CNS) leukemia, who are in blast transformation of chronic myeloid leukemia (CML), or whose AML is classified as favorable according to the European Leukemia Net (ELN) |
Diagnosi di leucemia promielocitica acuta o diagnosi di leucemia del sistema nervoso centrale, in pazienti che siano in trasformazione blastica della leucemia mieloide cronica; classificazione della LMA come favorevole secondo ELN, European Leukemia Net |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall survival |
Tempo di sopravvivenza |
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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) |
Quality of life and patient reported outcomes (FACT leukemia and EQ 5D5L QoL) |
Qualità della vita e outcomes riportati dal paziente (FACT leucemia e EQ 5DL QoL) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Migliore Scelta Terapeutica del Medico Curante tra i 3 regimi proposti dal protocollo |
Physician’s Choice as described in the protocol |
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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 | 7 |
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 | 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 |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 8 |
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 | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |