E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
newly diagnosed high-risk acute promyelocytic leukemia (APL) |
Leucémie Aiguë Promyélocytaire (LAP) de haut risque nouvellement diagnostiquée |
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E.1.1.1 | Medical condition in easily understood language |
newly diagnosed high-risk acute promyelocytic leukemia (APL) |
Leucémie Aiguë Promyélocytaire (LAP) de haut risque nouvellement diagnostiquée |
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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 | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10001019 |
E.1.2 | Term | Acute promyelocytic leukaemia |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 compare event-free survival (EFS) of the experimental treatment arm including ATO/ATRA and idarubicin with standard treatment based on ATRA plus chemotherapy (AIDA regimen) in newly diagnosed high-risk APL |
Comparer la survie sans évènement entre le bras de traitement expérimental (ATO/ATRA + 2 jours d’Idarubicine) et le traitement standard (ATRA + polychimiothérapie = schéma AIDA) |
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E.2.2 | Secondary objectives of the trial |
- complete remission (CR) , overall survival (OS) and cumulative incidence of relapse (CIR) rates - cumulative incidence of secondary myelodysplastic syndromes or acute myeloid leukaemia - early death during induction - quality of life - toxicity profile - kinetics of MRD - duration of in-patient treatment - health economics
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- Taux de rémission complète (RC), survie globale et incidence cumulée des rechutes - Incidence cumulée des SMD secondaires ou LAM - Décès précoce durant la phase d’induction - Qualité de vie - Profil de toxicité - Cinétique de la maladie résiduelle - Durée d’hospitalisation - Évaluation des coûts de santé |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Informed consent - women or man with a newly diagnosed APL by cytomorphology, confirmed by molecular analysis - Age ≥18 and ≤ 65 years - ECOG performance status 0-3 - WBC at diagnosis > 10 GPt/l - serum total bilirubin ≤ 3.0 mg/dl (≤ 51 µmol/l) - serum creatinine ≤ 3.0 mg/dl (≤ 260 µmol/l) - women must fulfill at least one of the following criteria in order to be eligible for trial inclusion: o Post-menopausal (12 months of natural amenorrhea or 6 months of amenorrhea with Serum FSH > 40 U/ml) o Postoperative (i.e. 6 weeks) after bilateral ovariectomy with or without hysterectomy o Continuous and correct application of a contraception method with a Pearl Index of <1% (e.g. implants, depots, oral contraceptives, intrauterine device – IUD). o Sexual abstinence o Vasectomy of the sexual partner
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- Les patients doivent comprendre et signer le consentement éclairé - Femme ou homme avec une LAP nouvellement diagnostiquée, confirmée par analyse moléculaire - Age ≥ 18 ans et ≤65 ans - ECOG ≤3 - GB >10G/L au diagnostic - Bilirubine sérique totale ≤3.0mg/dL (≤51µmol/L) - Créatinine sérique ≤3.0mg/dL (≤260 µmol/L) - Les femmes en âge de procréer doivent répondre au moins à un des critères ci-dessous pour être éligible : o Ménopause depuis au moins 6 mois avec taux de FSH>40U/mL ou plus de 12 mois d’aménorrhée o Ovariectomie bilatérale avec ou sans hystérectomie depuis au moins 6 semaines o Méthode de contraception efficace et continue o Abstinence o Vasectomie chez le partenaire sexuel |
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E.4 | Principal exclusion criteria |
- patients who are not eligible for chemotherapy as per discretion of the treating physician - APL secondary to previous radio- or chemotherapy for non-APL disease - other active malignancy at time of study entry (exception: Basal-Cell Carcinoma) - lack of diagnostic confirmation of APL at genetic level - Significant arrhythmias, ECG abnormalities - other cardiac contraindications for intensive chemotherapy (L-VEF <50%) - uncontrolled, life-threatening infections - severe non controlled pulmonary or cardiac disease - severe hepatic or renal dysfunction - HIV and/or active hepatitis C infection - pregnant or breast-feeding patients - allergy to trial medication or excipients in study medication - substance abuse; medical, psychological or social conditions that may interfere with the patients participation in the study or evaluation of the study results - use of other investigational drugs at the time of enrolment or within 30 days before study entry
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- Patients non éligibles à la chimiothérapie - LAP secondaire à une radiothérapie ou une chimiothérapie pour une autre maladie que la LAP - Autre cancer actif au moment de l’inclusion dans l’essai à l’exception des carcinomes baso-cellulaires - Absence de confirmation du diagnostic de LAP au niveau génétique - Arythmies significatives ou ECG anormal : o Syndrome du QT long o Historique de tachyarythmie ventriculaire ou atriale o Bradycardie cliniquement significative (<50BPM) o QTc >500msec au screening o Bloc de branche - Autre contre-indication cardiaque à la chimiothérapie (LVEF<50%) - Infections non contrôlées - Affections cardiaques ou pulmonaires sévères non contrôlées - Altération sévère de la fonction hépatique ou de la fonction rénale - Infection chronique connue par le VIH, VHB, VHC - Sclérose en plaques active - Femmes enceintes ou allaitantes - Allergie connue au traitement à l’étude ou à ses excipients - Toxicomanie - Condition médicale, psychiatrique empêchant le suivi de l’essai - Utilisation d’un autre traitement à l’essai dans les 30 jours précédant l’inclusion - Absence d’assurance maladie |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the study is event-free survival. |
Le critère principal de l’étude est la survie sans évènement. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary endpoint of the study is event-free survival. This is a time to event endpoint. This cumulative endpoint includes the following events: no achievement of hematological complete remission after induction therapy; no achievement of molecular remission after the last consolidation course (molecular resistance); relapse (hematological/molecular); death including early death (within 30 days after randomization) or development of secondary myelodysplasia or leukemia. |
Le critère principal de l’étude est la survie sans évènement. Ce critère inclus les évènements suivants : absence de rémission hématologique complète après la phase d’induction ; absence de rémission moléculaire après le dernier cycle de consolidation (Bras A après 4 cycles ; bras B après 3 cycles)(résistance moléculaire) ; rechute (hématologique / moléculaire) ; décès incluant les décès précoces (dans les 30 jours après la randomisation) ou apparition d’une myélodysplasie secondaire ou d’une leucémie |
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E.5.2 | Secondary end point(s) |
- complete remission (CR), overall survival (OS) and cumulative incidence of relapse (CIR) rates - cumulative incidence of secondary myelodysplastic syndromes or acute myeloid leukaemia - early death during induction - quality of life - toxicity profile - kinetics of MRD - duration of in-patient treatment - health economics
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- Taux de rémission complète (RC), survie globale et incidence cumulée des rechutes - Incidence cumulée des SMD secondaires ou LAM - Décès précoce durant la phase d’induction - Qualité de vie - Profil de toxicité - Cinétique de la maladie résiduelle - Durée d’hospitalisation - Évaluation des coûts de santé |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
-whole study |
Totalité de l'essai |
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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 | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 |
schéma standard de traitement des LAP |
standard of care treatment according to European Guidelines |
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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 | 27 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
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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LVLS |
Dernière visite du dernier patient |
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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 | 66 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 66 |