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 |
Leukemia, cancer in bone marrow and blood |
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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 | 10000886 |
E.1.2 | Term | Acute myeloid leukemia |
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 |
To assess, in a randomized study the value of Azacitidine as post remission therapy (in comparison to observation) in elderly patients with AML, RAEB or RAEB-t with respect to the disease free survival. |
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E.2.2 | Secondary objectives of the trial |
Post remission Azacitidine therapy will be evaluated with respect to toxicity, probability of relapse and probability of death in first CR and overall survival.
To evaluate prognostic factors (e.g. phenotype, cytogenetics) in the context of post remission therapy with Azacitidine as regards to overall survival, and disease free survival.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Age 60 years or more
2) Subjects with a cytopathologically confirmed diagnosis of
(a) AML (M0-M2 and M4-M7, FAB classification, appendix A), or
(b) refractory anemia with excess of blasts (RAEB) or refractory anemia with
excess of blasts in transformation (RAEB-t) with an IPSS score of >1.5
Note: Subjects with a secondary AML progressing from antecedent myelodysplasia and biphenotypic leukaemia are eligible.
3) Less than 5% bone marrow blasts and absence of Auer rods after 2 cycles of induction therapy (this induction therapy can be according to HOVON81, HOVON92 or similar protocols. Of note: also patients who are treated according to one of these protocols but were not formally included in these studies are eligible for HOVON97)
4) Hematological recovery, i.e. ANC ³ 0.5 x 109/l and platelets ³ 50 x 109/l
5) WHO performance status £ 2 (see appendix F)
6) Written informed consent
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E.4 | Principal exclusion criteria |
1) Extramedullary disease
2) Planned allogeneic hematopoietic cell transplantation
3) Previous polycythaemia rubra vera
4) Primary myelofibrosis
5) Blast crisis of chronic myeloid leukemia
6) AML-FAB type M3 or AML with cytogenetic abnormality t(15;17)
7) Impaired hepatic or renal function as defined by:
a) ALT and/or AST > 2.5 x normal value
b) Bilirubin > 2 x normal value
c) Serum creatinin > 2 x normal value (after adequate hydration)
8) Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, cancer, etc.)
9) Cardiac dysfunction as defined by:
a) Myocardial infarction within the last 6 months of study entry, or
b) Reduced left ventricular function with an ejection fraction <50%
c) Unstable angina
d) Unstable cardiac arrhythmias
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E.5 End points |
E.5.1 | Primary end point(s) |
Disease-free survival measured from the date of randomization to relapse or death from any cause whichever comes first. See appendix D for definition of relapse. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The final analysis of the primary endpoints will be done one year after
last patient has gone off protocol treatment. |
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E.5.2 | Secondary end point(s) |
•Overall survival measured from the date of randomization
•Probability of relapse and death after inclusion from date of
randomization calculated as competing risks.
•Number and duration of hospitalization as well as transfusion
requirements (red cell and platelet transfusion).
•Adverse events (according to Appendix E) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The final analysis of the primary endpoints will be done one year after
last patient has gone off protocol treatment. |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
prognostic factor evaluation |
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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) | 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 |
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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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
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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End of trial will be the date on which of all patients clean data including 1 year follow up of the last patient entered will be available |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |