Randomized Phase III Study of Decitabine +/- Hydroxyurea (HY) Versus HY in Advanced Proliferative CMML

Inclusion Criteria:

* Age ≥ 18
* CMML diagnosis according to WHO criteria Stable excess in blood monocytes, \> 1 G/L Lack of bcr-abl rearrangement (or Philadelphia chromosome) Bone marrow blast cells \< 20% Dysplasia of at least one lineage or clonality marker or blood monocytosis during more than 3 months w/o other explanation Blood and marrow smears will be reviewed at each country's level, but morphologist meetings at the 3 country level are planned for better harmonization and review of difficult cases
* WBC ≥ 13 G/L Measured on two successive CBC at least two weeks apart, outside of a context of infection.
* Either D1 or D2

D1: At least two of the following criteria, reviewed at each country's level: (modified from Wattel et al. Blood 1996) Marrow blasts \>= 5 % Clonal cytogenetic abnormality (other than t(5;12) (q33; p13) and isolated loss of Y chromosome ) Anemia (Hb \< 10 g/dL) ANC \> 16 G/l (in absence of infection) Thrombocytopenia (platelet count \< 100 G/L) Splenomegaly \> 5 cm below costal margin (spleen size should also be measured by an imaging technique)

Or:

D2: Extramedullary involvement: Including documented cutaneous, pleural or pericardial effusion.

* No prior treatment (except supportive care, or ESA, or short term (\< 6 weeks) HY in patients presenting with high WBC counts)
* Performance status 0-2 on the Eastern Cooperative Oncology Group (ECOG) Scale.
* Adequate organ function including the following Hepatic : total bilirubin \< 1.5 times upper limit of normal (ULN) (except moderate unconjugated hyperbilirubinemia due to intra medullary hemolysis or Gilbert syndrome) , alanine transaminase (ALT) and aspartate transaminase (AST) \< 3xULN Renal : serum creatinine \< 2 x ULN
* Signed Informed consent
* Negative pregnancy and adequate contraception (including in male patients wishing to father) if relevant.

Exclusion Criteria:

* Myeloproliferative / myelodysplastic syndrome other than CMML
* CMML with t(5 ;12) or PDGFBR rearrangement that may receive imatinib
* Patients eligible for allogeneic bone marrow transplantation with an identified donor
* Pregnant or breastfeeding
* Performance status \> 2 on the ECOG Scale.
* Serious concomitant systemic disorder, including active bacterial, fungal or viral infection that in the opinion of the investigator would compromise the safety of the patient and/or his/her ability to complete the study
* Prior malignancy (except in situ cervix carcinoma, limited basal cell carcinoma, or other tumors if not active during the last 3 years)