E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with newly diagnosed c-KIT or FLT3-ITD mutated t(8;21) AML |
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E.1.1.1 | Medical condition in easily understood language |
patients with newly diagnosed c-KIT or FLT3-ITD mutated t(8;21) Acute Myeloid Leukemia |
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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 | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10060557 |
E.1.2 | Term | Acute myelocytic 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 assess the efficacy of tyrosine-kinase inhibitor midostaurin in c-KIT or FLT3-ITD mutated t(8;21) AML
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Diagnosis of c-KIT and/or FLT3-ITD mutated t(8;21) AML i.e.
o >20% myeloid blasts in bone marrow and/or peripheral blood at initial diagnosis
o Plus cytogenetic diagnosis of aberration t(8;21)/AML1-ETO
o Plus mutation of c-KIT gene (mut-KIT17 or mut-KIT8) or FLT3-ITD mutation or both c-KIT and FLT3-ITD mutations
• Chemo-responsive disease* as determined by early bone marrow assessment on day 14-16 after first cycle of standard induction therapy with seven-day continuous infusion of 100-200 mg/m2 cytarabine per day in combination with three doses of daunorubicine, or idarubicine, or mitoxantrone
• Age 18 – 65 years
• Fit for intensive chemotherapy as assessed by
o Adequate liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening:
Total bilirubin ≤ 1.5 times the upper limit of normal
ALT and AST ≤ 2.5 times upper limit of normal
Creatinine ≤ 1.5 times upper limit of normal
o Adequate cardiac function, i.e. left ventricular ejection fraction (LVEF) of >= 50% as assessed by transthoracal twodimensional echocardiography (“M Mode”) or MUGA scan
• ECOG performance status of 0-2
• Life expectancy of at least 12 weeks
• Subject's written informed consent has been obtained
• Legal capacity (see also exclusion criterion) |
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E.4 | Principal exclusion criteria |
- Primary refractory or previously relapsed AML
- Non-eligibility for high-dose cytarabine based consolidation, e.g. intolerance to cytarabine
- Inability to swallow oral medications
- Symptomatic congestive heart failure as defined by left ventricular ejection fraction (LVEF) of ≤50% as assessed by transthoracal twodimensional echocardiography (“M Mode”) or MUGA scan
- Subject without legal capacity who is unable to understand the nature, significance and consequences of the study
- Investigational drug therapy outside of this trial during or within 4 weeks of study entry
- Known or persistent abuse of medication, drugs or alcohol |
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E.5 End points |
E.5.1 | Primary end point(s) |
2-year event-free Survival |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
evaluation during study and in follow-up visits up to 2 year after study entry |
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E.5.2 | Secondary end point(s) |
Time to relapse (TTR), Cumulative incidence of relapse (CIR), Overall survival (OS), Relapse-free survival (RFS), morphologic and molecular CR rate, incidence of AEs/SAEs, MRD kinetics |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
evaluation during study and in follow-up visits up to 2 year after study entry |
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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 | 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.8.3 |
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 | 12 |
E.8.5 | The trial involves multiple Member States | No |
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 | No |
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 | 7 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |