E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated | |
E.1.1.1 | Medical condition in easily understood language |
Acute growth of certain cell types which have an orginin in the bone marrow |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10024348 |
E.1.2 | Term | Leukemia myelogenous |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000835 |
E.1.2 | Term | Acute 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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10024307 |
E.1.2 | Term | Leukaemia myelogenous |
E.1.2 | System Organ Class | 100000004864 |
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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 |
Investigate whether consolidation treatment with repeated courses of azacitidine prolongs leukemia–free survival (LFS) as compared to standard consolidation chemotherapy in elderly (≥65y) patients with AML in CR1. |
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E.2.2 | Secondary objectives of the trial |
Study whether consolidation treatment with azacytidine, as compared with the control arm,
improves overall survival (OS)
- Assess the relationship between azacitidine treatment and DNA-methylation patterns
- Assess the clinical outcome according to molecular mutations and cytogenetic aberrancies at diagnosis
- Assess safety, tolerability of azacitidine when given after standard induction chemotherapy (DA) in elderly patients with AML
- Assess quality of life in patients receiving consolidation with azacitidin and standard chemotherapy, repsectively
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subjects >=65 years of age at the time of signing the informed consent form
2. A confirmed diagnosis of AML according to the 2008 WHO classification
• This includes: Bone marrow aspirate with a good clot or biopsy for morphology, flow cytometry, cytogenetic analysis, and in case of normal cytogenetics, molecular genetic analyses including FLT3-ITD, NPM-1 and CEBPA
• Biobanking of leukemic cells at diagnosis performed (according to guidelines of the Swedish National AML biobank).
3. A documented CR or CRp achieved after one or two induction courses.
• CR is defined as
- bone marrow blasts < 5% with regenerating hematopoiesis
- no extramedullary leukemia
- independency of erythrocyte transfusions
- neutrophils > 1.0 x 10(9)/L
- platelets > 100 x 10(9)/L
• Criteria for complete remission with low platelet count (CRp):
- A patient fulfilling bone marrow and peripheral blood criteria for CR in AML but who has a lower platelet count than 100 x 10(9) may also be considered CR (CRp) provided platelet count is stable and greater than 30 x 10(9) and there is no bleeding symptoms.
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E.4 | Principal exclusion criteria |
1. Subjects who are not considered to be candidates to complete the consolidation therapy due to medical or psychological reasons.
2. Subjects who have taken any investigational drugs or participated in an interventional clinical trial within 30 days prior to screening.
3. Patients with acute promyelocytic leukemia
4. Patients with t(8;21) or inv(16)
5. CNS leukemia
6. Patients with a previous diagnosis of MDS, i.e. AML preceeded by a diagnosed MDS
7. Subjects who are candidates for allogeneic stem cell transplantation (SCT)
8. Another cancer diagnosis with a life expecancy of less than two years
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E.5 End points |
E.5.1 | Primary end point(s) |
LFS at 12 months after start of induction chemotherapy (DA) |
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E.5.2 | Secondary end point(s) |
- OS 2 years after start of induction chemotherapy (DA)
- Analysis of a broad spectrum of molecular and cellular events relating to the epigenetic status of the malignant cells. These events will be used to identify biomarkers for successful consolidation and to address whether AML cases that relapse while on the study are molecularly and epigenetically different between those given azacitidine or DA consolidation
- Treatment related morbidity and mortality
- SAE until two months after the last course of consolidation
- No of consolidation courses actually given.
- No of days in hospital during the period of 12 months from start of consolidation treatment as well as quality of life during and after consolidation.
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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 | 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 | 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 | 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) | Yes |
E.8.2.2 | Placebo | No |
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 | 10 |
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 | Information not present in EudraCT |
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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Five years (follow-up of survival) after the inclusion of the last patient, unless closed prematurely at the interim analysis. |
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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 | 9 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |