E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute Myeloid Leukemia (AML) |
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E.1.1.1 | Medical condition in easily understood language |
Acute Myeloid Leukemia (AML) |
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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. |
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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, morphologic leukemia-free state (MLFS), 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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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 one prior AML therapy (must have included 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. |
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E.4 | Principal exclusion criteria |
Patients with acute promyelocytic leukemia (AML M3), known central nervous system (CNS) leukemia, or who are in blast transformation of chronic myeloid leukemia (CML), or whose AML is classified as favorable according to the European Leukemia Net (ELN) disease risk assessment will be excluded from this study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall survival (OS) is the primary efficacy endpoint of this study. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The interim analysis will take place after 62 (50%) OS events. |
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E.5.2 | Secondary end point(s) |
Secondary efficacy endpoints will include the following, assessed in hierarchical fashion in the order presented below: • The proportion of patients whose OS is at least 3 months (OS3.0), • The complete remission rate (CRR) including complete remission with full hematologic recovery (CR), and median disease free survival (DFS), for patients who achieve CR, • The modified CRR (mCRR), including CR or CRi (including CRp) and median DFS for patients who achieve CR or CRi (including CRp), • The overall response rate (ORR) and duration of overall response (DOR), including CR, CRi, MLFS, and partial remission (PR), • The disease control rate (DCR) defined as ORR + stable disease for ≥ 4 weeks (SD), and duration of DCR, • Quality of life and patient reported outcomes (FACT-Leukemia and EQ-5D-5L) (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 | 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 | 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 |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 38 |
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 |
Belgium |
Canada |
Denmark |
France |
Germany |
Israel |
Italy |
Netherlands |
Spain |
United Kingdom |
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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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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
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 | 0 |