E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute Myeloid Leukaemia (AML) |
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MedDRA Classification |
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 |
1. Estimate rate of complete remission (CR), including complete remission except for platelet count < 100 x 109/L (CRp) (CR + CRp rate) in patients with AML who have not attained blast clearance after the first course of a ara-C based remission-induction therapy. |
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E.2.2 | Secondary objectives of the trial |
2. Obtain indication on the independence between hENT1 expression level and CR or CRp 3. Obtain guidance on disease free survival (DFS), defined as time from CR + CRp to relapse 4. Obtain guidance on event free survival (EFS), defined as time from day one of therapy until relapse or death from any cause 5. Characterize the safety profile of elacytarabine plus idarubicin in this patient population
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients with a confirmed diagnosis of AML according to WHO classification (excluding acute promyelocytic leukaemia) 2. Patients who have received one previous standard dose ara-C-containing regimen aiming at induction of complete remission (CR) and who have more than 5 % remaining blast cells in bone marrow on day (d) 14 ± 2, or by other means documented residual disease (i.e. circulating blasts, persistent chloromas, other evident disease). 3. Patients from whom samples for determination of hENT1 status on leukemic blast cells can be taken and prepared at diagnosis and/or at baseline 4. Patients must be 18 years of age or older 5. Patients must have ECOG performance status (PS) of 0 – 2 6. Left ventricular ejection fraction (LVEF) must be ≥ 45 % as measured by MUGA scan or 2D ECHO within 14 days prior to start of therapy. 7. Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must have a negative serum or urine pregnancy test within 2 weeks prior to beginning treatment on this study 8. Male and female patients must use acceptable contraceptive methods for the duration of time on study, and males also for 3 months after the last elacytarabine dose 9. Patients must be capable of understanding and complying with parameters as outlined in the protocol, and able and willing to sign a written informed consent form 10. Patients must have the following clinical laboratory values: • Serum creatinine ≤ 1.5 x the institutional upper limit of normal (ULN) • Total bilirubin ≤ 1.5 x the ULN according to national prescribing information unless considered due to Gilbert’s syndrome • Alanine aminotransferase (ALT) (SGPT), or aspartate aminotransferase (AST) (SGOT) ≤ 2.5 x the ULN unless considered due to organ leukemic involvement 11. Patients must be eligible for administration of idarubicin according to current national prescribing information for idarubicin
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E.4 | Principal exclusion criteria |
1. A history of allergic reactions to egg, idarubicin and/or other anthracyclines or other components of the products A history of allergic reactions to ara-C of CTCAE grade 3 or 4 2. Persistent clinically significant and relevant toxicities from the previous course of chemotherapy 3. A cancer history, that according to the investigator might confound the assessment of the study endpoints 4. Patients with prior treatment with a cumulative dose of doxorubicin or equivalent exceeding 300 mg/m2 according to the following calculation index: X/300 + Y/160 < 1 where X is the doxorubicin or equivalent dose in mg/m2 and Y is the mitoxantron dose in mg/m2. These calculations are to be used as guidance as there is no maximum cumulative dose defined in the summary of product characteristics (SPC) for idarubicin. The patient should tolerate minimum one course of combination therapy 5. Active heart disease including myocardial infarction within the previous 3 months, symptomatic coronary disease, arrhythmias not controlled by medication, or uncontrolled congestive heart failure. Any NYHA grade 3 or 4 6. Known positive status for human immunodeficiency virus (HIV) or hepatitis B or C 7. Pregnant and nursing patients are excluded because the effects of elacytarabine on a foetus or a nursing child are unknown 8. Uncontrolled intercurrent illness including, but not limited to uncontrolled infection, or psychiatric illness/social situations that may reduce compliance with study requirements 9. Patients receiving hydroxyurea within the last 12 hours prior to treatment on this protocol or any other investigational or standard cytotoxic treatment within the last 14 days, except the first remission-induction course 10. Any medical condition, which in the opinion of the investigator places the patient at an unacceptably high risk for toxicities
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E.5 End points |
E.5.1 | Primary end point(s) |
• Incidence of CR + CRp • hENT1 status in blast cells • Relation between hENT1 expression level and CR + CRp • Relapse or death • Clinical and laboratory adverse events (AEs)
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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 | 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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
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 | 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 | 1 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 9 |