E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
AML is a malignant condition of the bone marrow. It results in failure of the bone marrow to manufacture enough blood cells because the marrow contains too many leukaemia cells |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10005329 |
E.1.2 | Term | Blood and lymphatic system disorders |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
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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 trial is designed to identify whether the addition of these new agents will improve the efficacy of the current standard treatment, without excessive toxicity.
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E.2.2 | Secondary objectives of the trial |
During the trial we will also capture data about response to treatment, early (30-day and 8-week) mortality and any additional information relating to one of the drugs in particular (for instance, cardiac assessments).
Supportive care requirements will also be noted, to inform the health economics aspect of treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•They have one of the forms of acute myeloid leukaemia, except Acute Promyelocytic Leukaemia or CML in blast crisis as defined by the WHO Classification (Appendix A) — this can be any type of de novo or secondary AML
•They have received a first induction chemotherapy course (Daunorubicin 3+10)
•Have a FLT3 mutation
•Serum Creatinine ≤ 1.5 × ULN (upper limit of normal)
•Serum Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤2.5 × ULN
•Serum lipase or amylase ≤1.5 × ULN
•Serum potassium, magnesium, and calcium levels should be at least within institutional normal limits, and every effort should be made to keep potassium at institutional normal limits, and every effort should be made to keep magnesium concentrations above 4.0 mEq/dL, and serum calcium at normal concentration
•Female and Male patients who are of childbearing potential must agree to use an effective form of contraception with their sexual partners while on study drug.
•Age 18 to 60 years
•Provided written informed consent
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E.4 | Principal exclusion criteria |
•They have previously received cytotoxic chemotherapy other than the combination of Daunorubicin/ Ara-C as the first induction treatment.
•They do not have documented a FLT3 mutation.
•They are in blast transformation of chronic myeloid leukaemia (CML)
•They have a concurrent active malignancy or a malignancy under treatment excluding basal cell carcinoma
•They are pregnant or lactating
•They have Acute Promyelocytic Leukaemia
•Leukaemia involving the central nervous system.
•Known infection with human immunodeficiency virus (HIV)
•History of acute pancreatitis within 1 year of study or history of chronic pancreatitis
•History of alcohol abuse
•Have uncontrolled hypertriglyceridemia (triglycerides >450 mg/dL)
•Significant uncontrolled or active cardiovascular disease, specifically including, but not restricted to: a. Myocardial infarction, unstable angina and/or congestive heart failure within 3 months prior to randomization b. History of clinically significant (as determined by the treating physician) atrial arrhythmia; or any ventricular arrhythmia
•Uncontrolled hypertension (diastolic blood pressure >100 mm Hg; systolic >150 mm Hg)
•Taking medications that are known to be associated with Torsades de Pointes (Appendix C)
• Malabsorption syndrome or other gastrointestinal illness that could affect oral absorption of study drugs
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E.5 End points |
E.5.1 | Primary end point(s) |
• Relapse Free Survival at 12 months • Response (CR, CRi, PR) achievement, and reasons for failure • 30 day and 8 week mortality • Toxicity, both haematological and non-haematological • Supportive care requirements
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E.5.2 | Secondary end point(s) |
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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 | 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 | 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 | 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) | Yes |
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 | 150 |
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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Last patient, last treatment. |
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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 | 3 |
E.8.9.1 | In the Member State concerned days | 1 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 1 |