Decitabine in Patients With Chronic Myelomonocytic Leukemia (CMML)

A Phase II Study of Decitabine in Patients With Chronic Myelomonocytic Leukemia

The aim of this study is to determine the therapeutic efficacy of Decitabine in patients with chronic myelomonocytic leukemia (CMML) diagnosis according to WHO criteria either untreated or previously treated with Hydrea or Etoposide (given orally), non intensive chemotherapy or intensive chemotherapy given more than 3 months before inclusion.

Inclusion Criteria:

• Age 18 or older

• CMML diagnosis according to WHO criteria

• Stable excess in blood monocytes,>1x10G/l and >10% of WBC

• Bone marrow blasts <20%

• Dysplasia of at least one lineage or clonality marker or blood monocytosis during more than 3 months w/o other explanation

• With:

  • if WBC < or= 12 000/mm3: IPSS high or intermediate 2
  • if WBC > 12 000/mm3: at least two of the following criteria: blast cells > 5% in the bone marrow, clonal cytogenetic abnormality other than t(5;12)(q33;p13), anemia (Hb < 100 g/l), thrombocytopenia (platelet count < 100G/l), splenomegaly > 5 cm below costal margin, extramedullary localization

• Either untreated or previously treated with

• Hydrea or Etoposide given orally

• non intensive chemotherapy

• intensive chemotherapy given more than 3 months before inclusion

• With performance status 0-2 on the ECOG scale

• With estimated life expectancy of at least 12 weeks

• With adequate organ function including the following:

  • Hepatic: total bilirubin < 1.5 times upper limit of normal (ULN), alanine transaminase (ALT) and aspartate transaminase (AST) < 3 times ULN
  • Renal: serum creatinine < 1.5 times ULN, creatinine clearance > 30 ml/min

• With informed consent

• Negative pregnancy and adequate contraception if relevant

Exclusion Criteria:

• Myeloproliferative/myelodysplastic syndrome other than CMML
• Acute blastic transformation of CMML with bone marrow blasts>20%
• Patients eligible for allogenic bone marrow transplantation with identified donor
• CMML with t(5;12) or PDGFbetaR rearrangement that could receive Imatinib
• Previous treatment with a hypomethylating agent
• Age < 18 years old
• Pregnancy or breastfeeding
• Performance status> 2 on the ECOG Scale
• Estimated life expectancy < 12 weeks
• 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