E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with high risk myelodysplastic syndrome or acute myeloid leukemia |
Patients atteints d'un syndrome myélodysplasique de haut risque ou d'une leucémie aigüe myéloblastique |
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E.1.1.1 | Medical condition in easily understood language |
high risk myelodysplastic syndrome or acute myeloid leukemia |
syndrome myélodysplasique de haut risque ou leucémie aigüe myéloblastique |
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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 | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000886 |
E.1.2 | Term | Acute myeloid leukemia |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028534 |
E.1.2 | Term | Myelodysplastic syndrome NOS |
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 |
Achieving a disease-free survival of 35% (expected 12%), 12 months after transplant |
Atteindre 35% de survie sans maladie (attendu 12%) à 12 mois après la greffe de moelle osseuse |
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E.2.2 | Secondary objectives of the trial |
-Proportion of patients receiving allo SCT
-Proportion of patients eligible for post-transplant oral decitabine
-Proportion of patients eligible for post-transplant DLI
-Grade III/IV toxicities
-Non-relapse mortality
-Proportion of patients completing treatment schedule
-Overall survival at 12 and 24 months, DFS at 24 months after transplant
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-Proportion de patients ayant reçu la greffe de moelle osseuse
-Proportion de patients éligibles au traitement de maintenance après la greffe
-Proportion de patients éligibles à une infusion de lymphocytes du donneur
-Toxicités de grade III/IV
-Taux de mortalité sans rechute
-Proportion de patients ayant reçu 10 cures de maintenance
-Survie globale à 12 et 24 mois, survie sans maladie à 24 mois après la greffe
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patients aged from 18 to 70 years
- MDS or AML with unfavorable genetics defined as follow:
-4 or more cytogenetic abnormalities or
-3 cytogenetic abnormalities and TP53 or other unfavorable mutations (ASXL1, RUNX1) or
-3 cytogenetic abnormalities and monosomal karyotype or
-mutations involving EVI1
- AML patients should have received chemotherapy
- Marrow blast < 20% for MDS and < 10% for AML post chemotherapy
- Non-proliferative disease
- A donor is available (HLA matched or mismatched)
- Adequate contraception in women < 50 years and for men. Subjects must agree to use, and to be able to comply with, effective contraception without interruption, at least the first six months after transplant, throughout the entire duration of study drug therapy and for 3 months after the last dose of study drug therapy.
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- Patients âgés de 18 à 70 ans
- SMD ou LAM avec caryotype défavorable, défini par :
-4 anomalies cytogénétiques ou plus, ou
-3 anomalies cytogénétiques et mutation TP53 ou autre mutation défavorable (ASXL1, RUNX1), ou
-3 anomalies cytogénétiques et caryotype monosomal, ou
-Mutations impliquant le gène evi1
-Chimiothérapie préalable pour les patients atteints de LAM
-Blastes médullaires < 20 % pour les SMD et < 10 % post chimiothérapie pour les LAM
-Maladie non-proliférative
-Donneur identifié (HLA compatible ou non-compatible)
-Contraception adéquate chez les femmes de moins de 50 ans et chez les hommes. Les patients doivent accepter d'utiliser une contraception efficace sans interruption, au moins les six premiers mois après la greffe, pendant toute la durée du traitement à l'étude et pendant 3 mois après la dernière dose du traitement à l'étude
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E.4 | Principal exclusion criteria |
- ECOG 3 or more
- Cancer less than 2 years before inclusion or cancer not in remission the last 2 years before inclusion (except in situ cancer or baso cellular cancer)
- Cardiac failure with EF < 50%
- Creatininemia level > 150 µmol/L
- Liver enzyme > 3 N
- Conjugated bilirubinemia > 25 µmol/L
- MDS occurring in patients with Fanconi anemia or congenital dyskeratosis
- Proliferative disease in patients not in remission: WBC > 15 G/L or use of continuous cytotoxic to maintain WBC < 15 G/L
- AML with marrow or peripheral blast count higher than 10% after chemotherapy
- No contraception
- Pregnant or breastfeeding women
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-ECOG ≥ 3
-Cancer actif ou antécédent de cancer dans les 2 années précédant l’inclusion (à l’exception du cancer in situ ou cancer baso-cellulaire)
-Déficience cardiaque avec FEVG <50 %
-Créatinémie > 150 µmol/L
-Enzymes hépatiques > 3 N
-Bilirubine conjuguée > 25 µmol/L
-SMD survenant chez des patients atteints par une anémie de Fanconi ou une dyskératose congénitale
-Maladie proliférative active : taux de leucocytes > 15 G/L ou utilisation en continu d’agents cytotoxiques dans le but de maintenir un taux de leucocytes < 15 G/L
-LAM avec blastes > 10 % après chimiothérapie
-Absence de contraception
-Femme enceinte ou allaitante
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E.5 End points |
E.5.1 | Primary end point(s) |
DFS at 1 year post transplant |
Survie sans maladie à 1 an après la greffe |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Overall survival from the date of transplantation and from the date of inclusion at 1 year and 2 years
- Risk factors for DFS, OS NRM at 1 year and 2 years
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-Survie globale à 1 an et à 2 ans après la greffe et depuis l’inclusion
-Facteurs de risque pour la survie sans maladie, la survie globale et la mortalité sans rechute à 1 an et à 2 ans
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At 1 and 2 years |
A 1 an et 2 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 | 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 | 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) | 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 | 14 |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |