A Study of Eltrombopag in Patients With CMML and Thrombocytopenia

Treatment of patients with chronic myelomonocytic leukemia (CMML) and thrombocytopenia.

All eligible patients will be treated with eltrombopag for a minimum of twelve weeks and a maximum of 24 months.

Eligibility Criteria:
Inclusion Criteria:

* Age 18 years or older
* Chronic myelomonocytic leukemia (CMML) 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
* Platelet counts \< 50 G/L on two successive blood counts in the 2 weeks preceding inclusion
* Either of D1 or D2 criteria:
* Lack of features of advanced disease If white blood cell count (WBC) \< 13 G/L: International Prognostic Scoring System (IPSS) low or intermediate-1

If WBC ≥ 13 G/L: no more than one of the following criteria:

* Clonal cytogenetic abnormality other than t(5;12) (q33; p13)
* Absolute neutrophil count (ANC) \> 16 G/L
* Anemia (Hb \< 100 g/L)
* Extramedullary localization (documented cutaneous, pleural or pericardial effusion, etc...) OR D2- Features of advanced disease If WBC \< 13 G/L: IPSS intermediate-2 or high

If WBC ≥ 13 G/L: two or more of the following criteria:

* Clonal cytogenetic abnormality other than t(5;12) (q33; p13)
* ANC \> 16 G/L
* Anemia (Hb \< 100 g/L)
* Extramedullary localization (documented cutaneous, pleural or pericardial effusion, etc...) And having resisted (progression or stable disease without hematological improvement according to International Working Group (IWG) 2006 criteria) or relapsed after a treatment with a hypomethylating agent (azacitidine or decitabine for a minimum of 6 cycles)
* Blast cells ≤ 5% in the bone marrow
* Performance status 0-2 on the Eastern Cooperative Oncology Group (ECOG) Scale
* Serum Creatinin \< 2 times the upper limit of normal (ULN)
* Alanine transaminase (ALT) and aspartate transaminase (AST) \< 3 ULN, total bilirubin \< 1.5 ULN (except Gilbert Syndrome)
* Adequate contraception if relevant
* Signed informed consent

Exclusion Criteria:

* CMML with t(5 ;12) or Platelet-derived growth factor beta receptor (PDGFbetaR) rearrangement
* Acute blastic transformation of CMML with bone marrow blast cells \> 20%
* Bone marrow blast cells \> 5%
* Patients eligible for allogeneic bone marrow transplantation with an identified donor
* Intensive chemotherapy given less than 3 months before inclusion
* Pregnant or breastfeeding
* Hepatitis C infection
* Splenomegaly \> 16 cm by ultrasound or CT scan (Not Applicable in patients without palpable splenomegaly)
* Significant (grade II-IV) myelofibrosis (bone marrow trephine if bone marrow aspirate with poor cellularity, or features of myelofibrosis on the peripheral blood smear (teardrop erythrocytes)
* Clinically relevant thromboembolic risk factor which, in the investigator's opinion, is such that the benefit/risk ratio becomes unfavourable if platelet counts increase
* Liver cirrhosis (Child-Pugh score ≥ 5)
* Prior Cancer (except in situ cervix carcinoma, limited basal cell carcinoma, or other tumors if not active during the last 3 years)
* 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.
* Hypersensitivity to Eltrombopag