Azacytidine (Vidaza®) Versus Fludarabine and Cytarabine (Fluga Scheme) in Elderly Patients With Newly Diagnosed Acute Myeloid Leukemia

A PHASE III, MULTICENTRE, RANDOMIZED, OPEN LABEL CLINICAL TRIAL OF AZACYTIDINE (VIDAZA®) VERSUS FLUDARABINE AND CYTARABINE (FLUGA SCHEME) IN ELDERLY PATIENTS WITH NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA.

The hypothesis is that the replacement of the standard fludarabine and cytarabine based therapy by azacytidine could result in an improvement of RFS and OS rates in the experimental arm. To fulfill the medical needs in such frail and elderly population, improvements in terms of atileukemic efficacy in the azacytidine experimental arm should be attained without increasing the therapy-related toxicity or decreasing the patients QoL.

This is a multicenter, randomized 1:1, open, and at national level, Phase III clinical trial.

This study will be conducted in 3 phases of different duration:

1. Selection phase (up to 14 days from the signature of informed consent): informed consent and review of the inclusion and exclusion criteria performing the relevant assessments.
2. Treatment Phase (from the start of treatment until the end of cycle 9): Induction phase (3 cycles) and consolidation phase (cycles 4-9). Study visits during treatment will be weekly during the induction phase (first 3 cycles) and every 2 weeks until the end of the consolidation phase.
3. Follow-up phase: monthly monitoring will be performed on all patients until they have completed a minimum of 2 years from the start of treatment, whether or not they continue receiving azacitidine cycles or Mini-Fluga according to the protocol. Following these 24 months, follow-up will be carried out at least quarterly. Patients suffering disease progression or relapse of the disease, or being early withdrawn due to any of the reasons specified in the protocol will be followed-up for survival until the end of the study or until the death of all patients, whichever comes first.

Inclusion Criteria:

1. - Having voluntarily given informed consent before performing any test that is not part of

   routine care of patients.

2. - Age greater than or equal to 65.

3. - Morphological diagnosis of non-promyelocytic AML according to the WHO criteria.

4. - Newly diagnosed AML.

5. - ECOG performance status <4.

6. - Ability and willingness to comply with the schedule of study visits.

Exclusion Criteria:

1. - Genetic diagnosis of acute promyelocytic leukemia.

2. - Patients with AML secondary to myelodysplastic syndrome (MDS) or chronic myeloproloferative syndrome who have been previously treated with antileukemic agents

   (hypomethylating or standard chemotherapy). Treatment with hydroxyurea prior to randomization is allowed.

3. - Serum creatinine ≥ 250 mmol / l (≥ 2.5 mg/dL) (unless attributed to AML).

4. - Bilirubin, alkaline phosphatase or ALT > 5 times the value of the upper limit of normal (unless attributed to AML) .

5. - Presence of an active and/or non controlled pathology different to AML which is severe and life-threatening, that in the investigator's opinion, prevents the subject participation in the study.

6. - Other active concomitant malignancy or whose remission is less than one year from the screening day (except carcinoma in situ).

7. - Presence of any psychiatric illness or medical condition that, in the investigator's opinion, prevents the subject participation in the study.

8. - Life expectancy less than X months.

9. - Inability of the patient or his legal representative to understand and voluntarily sign the informed consent form.