E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
elderly patients > 60 years, with acute myeloid leukemia |
Patients agés de plus de 60 ans, atteints d'une Leucemie aigue Myeloblastique |
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E.1.1.1 | Medical condition in easily understood language |
elderly patients with acute myeloid leukemia |
Patients agés de plus de 60 ans, atteints d'une Leucemie aigue Myeloblastique |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
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 |
To compare overall survival rate at 12 months between the two arms, with or without 200 mg of Eltrombopag daily after induction chemotherapy. |
comparer le taux de survie global à 12 mois entre les deux bras, avec ou sans l'administration d'eltrombopag 200 mg/J apres une chimiotherapie d'induction |
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E.2.2 | Secondary objectives of the trial |
- Response rate (CR and CRi) at day 45
- Leukemia Free Survival at 12 months
- Overall survival at 2, 3 and 5 years.
- Percentage of patients with platelets count > 100 G/L at day 45
- Time to platelet transfusion independence (more than 3 days with platelets ≥ 10 G/L)
- Number of accident haemorrhage event ≥ grade 3 until day 45
- Number of days with platelets < 10 G/L
- Number of platelets transfusion
- Time to platelets count > 100 G//L
- Time to PMN counts > 0.5 G/L
- Time to haemoglobin counts > 8 g/dl
- Time to red blood cells transfusion independence
- Safety assessment of eltrombopag utilizing NCI-CTC criteria v4.
- Evaluation of Quality of Life |
- le taux de réponse (RC et RCià à J45
- survie sans Leucemie à 12 mois
- survie globale à 2, 3 et 5 ans
- pourcentage de patients presentant des plaquettes > 100 G/L à J45
- delai d'obtention de l'independance transfusionnel en plaquettes (plus de 3 jours avec des palquettes ≥ 10G/L)
- nombre d'accident hemorragique de grade ≥ 3 jusqu'à J45
- nombre de jours avec des plaquettes < 10 G/L
- nombre de transfusion de plaquettes
- temps d'obtention des plaquettes > 100 G/L
- temps d'obtention des PNN > 0.5 G/L
- temps d'obtention une hemoglobine > 8g/dL
- temps d'obtention d'une independance transfusionnel en globule rouge
- evaluation de la toxicté d'eltrombopag en utilisant NCI-CTC criteria v4
- evaluation de la qualité de vie |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. 60 years of age.
2. AML de novo according to the WHO 2008 classification.
3. Subjects should be eligible for chemotherapy
4. ECOG < 3
5. SORROR ≤ 3
6. Informed consent to participate
7. Adequate baseline organ function defined by the criteria below:
• Total bilirubin ≤ 1.5xULN except cases clearly not indicative of inadequate liver function
• ALAT and ASAT ≤ 3xULN
• Creatinine ≤ 2.5xULN
• Adequate cardiac function with LVEF ≥50%
|
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E.4 | Principal exclusion criteria |
1. Subjects with a diagnosis of acute promyelocytic (M3) or megakaryocytic leukemia (M7).
2. AML with adverse cytogenetic according to the MRC 2010 classification.
3. AML secondary to MDS or MPN
4. Previous exposure to anthracycline.
5. Previous AML treatment other than hydroxyurea.
6. Any serious medical condition, laboratory abnormality, or psychiatric illness that would place the participant at an unacceptable risk or prevent them from giving informed consent.
7. History of thromboembolic event or other condition requiring ongoing use of anticoagulation either with warfarin or low molecular-weight heparin.
8. History of another malignancy within the past three years except basal cell carcinoma of the skin or carcinoma in situ of the cervix.
9. Pre-existing cardiovascular disease (including congestive heart failure, New York Heart Association [NYHA] Grade III/IV), or arrhythmia known to increase the risk of thromboembolic events (e.g. atrial fibrillation), or subjects with a QTc >450 msec (QTc >480 msec for subjects with Bundle Branch Block).
10. Patient requiring platelets transfusion with platelets > 10 x 109/L, for whatever reason.
11. History of treatment with romiplostim or other TPO-R agonists
12. Uncontrolled active infection.
13. Clinical symptoms suggesting active central nervous system leukemia.
14. Known active HIV, Hepatitis B or C infection
15. Pregnancy or breastfeeding
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E.5 End points |
E.5.1 | Primary end point(s) |
A 15% increase in the overall survival rate at 12 months with 200 mg of Eltrombopag daily |
une augmentation de la survie globale de 15% à 12 mois pour les patients recevant eltrombopag 200mg/J |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
A. Response rate (CR and CRi) at day 45
B. Leukemia Free Survival at 12 months
C. Overall survival at 2, 3 and 5 years.
D. Percentage of patients with platelets count > 100 x 109/L at day 45
E. Time to platelet transfusion independence (more than 3 days with platelets ≥ 10 x 109/L)
F. Number of accident haemorrhage event ≥ grade 3 until day 45
G. Number of days with platelets < 10 x 109/L
H. Number of platelets transfusion
I. Time to platelets count > 100 x 109/L
J. Time to PMN counts > 0.5 x 109/L
K. Time to haemoglobin counts > 8 g/dl
L. Time to red blood cells transfusion independence
M. Safety assessment of eltrombopag utilizing NCI-CTC criteria v4.
N. Evaluation of Quality of Life
|
A. Taux de réponse (RC and RCi) à Jour 45
B. Survie sans Leucémie à 12 mois
C. Survie globale à 2, 3, et 5 ans.
D. Pourcentage de patients avec des plaquettes > 100 x 109/L à J45
E. Délai d’obtention de l’indépendance transfusionnelle en plaquettes (plus de 3 jours avec des plaquettes ≥ 10 x 109/L)
F. Nombre d’accidents hémorragiques de grade ≥ 3 jusqu’à J45
G. Nombre de jours avec des plaquettes < 10 x 109/L
H. Nombre de transfusions de plaquettes
I. Délai d’obtention des plaquettes > 100 x 109/L
J. Délai d’obtention des PNN > 0.5 x 109/L
K. Délai d’obtention de l’hémoglobine > 8 g/dl
L. Délai d’obtention de l’indépendance transfusionnelle en globules rouges
M. Sécurité d’Eltrombopag selon les critères NCI-CTC v4.03
N. Evaluation de la qualité de vie |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
survival at 5 years |
survie à 5 ans |
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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 | 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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
E.8.2.3 | Other | No |
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 | 16 |
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
|
LVLS |
derniere visite de suivi du dernier patient ( 12 mois de recrutement + 13.5 mois de traitement + 60 mois de suivi soit au total 85.5 mois) |
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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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |