Open-label, randomized multicenter phase III non-inferiority study

Open-label, randomized, prospective multicenter phase III study to compare the role of HMT followed by HSCT vs HSCT upfront in HR-MDS with <10% of BM blasts and of CHT vs HMT followed by HSCT in HR-MDS with >10% BM blasts in terms of feasibility of HSCT (non-inferiority trial).

Inclusion Criteria:

1. Patients with newly diagnosed higher-risk MDS, including IPSS Intermediate-2 and high, and IPSS-R intermediate to very-high
2. Age 18-70 years
3. Previously untreated for HR-MDS
4. HSCT - eligible
5. Life expectancy ≥3 months;
6. Signed written informed consent according to ICH/EU/GCP and national local laws
7. Eastern Cooperative Oncology Group Performance Status Grade of 0-2

Exclusion Criteria:

1. Acute myeloid leukaemia with >20% blasts in BM or peripheral blood (PB);

2. concurrent malignancy diagnosed in the past 12 months (with the exception of skin basalioma);

3. severe renal, cardiac, liver or lung impairment;

4. pregnant or lactating or potentially fertile (both males and females), who have not agreed to avoid pregnancy during the trial period; Women of childbearing potential and men must agree to use effective contraception during and up to 3 months after treatment with azacitidine.

5. HIV infection; active, uncontrolled HCV or HBV infections or liver cirrhosis;

6. clinically relevant neurological or psychiatric diseases;

7. hypersensitivity (known or suspected) to AZA;

8. prior Treatments:

   1. prior investigational drugs (within 30 days);
   2. radiotherapy, chemotherapy, or cytotoxic therapy for non-MDS conditions within the previous 6 months;
   3. growth factors (EPO, G-CSF or GM-CSF) during the previous 21 days;
   4. androgenic hormones during the previous 14 days;
   5. prior transplantation or cytotoxic therapy, including azacitidine, AZA or chemotherapy, administered to treat MDS (a previous treatment with Lenalidomide is admitted, provided that lenalidomide had been stopped at least 60 days before enrolment).