- 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.- In addition, post remission Azacitidine…
ID
Source
Brief title
Condition
- Leukaemias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Disease-free survival measured from the date of randomization to relapse or
death from any cause whichever comes first.
Secondary outcome
- 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
Background summary
For elderly patients newly diagnosed with AML attaining CR, post-remission
chemotherapy consisting of high dose cytarabine has not provided significant
benefits due to enhanced toxicity. Marrow ablative cytotoxic stem cell
transplants are rarely applied in patients with AML of 60 yrs and older for
similar reasons. As a consequence, other avenues need to be pursued to prevent
relapse in complete responders of older age.
Recent studies have suggested that maintenance chemotherapy applied for several
months during remission in older patients with AML may reduce the frequency of
relapse
Morphologic (dysplasia) and cytogenetic criteria present in malignant blast
cells of elderly patients, suggest that AML and Myelodysplastic Syndromes (MDS)
might be associated diseases. It could be argued that elderly patients with
AML, who have less than 5% blasts in their bone marrow after intensive
chemotherapy, still have a disease comparable with MDS. These facts and the
efficacy of Azacitidine in MDS argue for the use of Azacitidine as maintenance
therapy after 2 cycles of intensive chemotherapy in patients with AML,
obviously at high risk of relapse.
Study objective
- 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.
- In addition, 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.
Study design
Prospective, multicenter, randomized phase III trial.
Intervention
maintenance therapy with Azacitidine or observation
Study burden and risks
The most common adverse effects of Azacitidine are myelosuppression, nausea and
vomiting and injection site reactions.
De Boelelaan 1117
Amsterdam 1081 HV
NL
De Boelelaan 1117
Amsterdam 1081 HV
NL
Listed location countries
Age
Inclusion criteria
- Age 60 years or more
- Subjects with a cytopathologically confirmed diagnosis of
(a) AML (M0-M2 and M4-M7, FAB classification)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.
- Less than 5% bone marrow blasts and absence of Auer rods after 2 cycles of induction therapy
- Hematological recovery, i.e. ANC >= 0.5 x 109/l and platelets >= 50 x 109/l
- WHO performance status <= 2
- Written informed consent
Exclusion criteria
- Extramedullary disease
- Planned allogeneic hematopoietic cell transplantation
- Previous polycythaemia rubra vera
- Primary myelofibrosis
- Blast crisis of chronic myeloid leukemia
- AML-FAB type M3 or AML with cytogenetic abnormality t(15;17)
- Impaired hepatic or renal function as defined by:
ALT and/or AST > 2.5 x normal value
Bilirubin > 2 x normal value
Serum creatinin > 2 x normal value (after adequate hydration)
- Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, cancer, etc.)
- Cardiac dysfunction as defined by:
Myocardial infarction within the last 6 months of study entry, or
Reduced left ventricular function with an ejection fraction <50%
Unstable angina
Unstable cardiac arrhythmias
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2008-001290-15-NL |
| CCMO | NL23888.042.08 |