A Study of Eltrombopag in Patients With CMML and Thrombocytopenia

Study Overview
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Brief Summary
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Treatment of patients with chronic myelomonocytic leukemia (CMML) and thrombocytopenia.

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

Official Title
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A Phase I/II Study of Eltrombopag in Patients With Chronic Myelomonocytic Leukemia and Thrombocytopenia

Conditions
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CMML, Thrombocytopenia

Intervention / Treatment
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* Drug: eltrombopag


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: eltrombopag<br> | Drug: eltrombopag<br>* initial dose of 50 mg once daily, then the dose can be sequentially increased every 2 weeks up to a maximum dose of 300mg/day<br>* Other names: revolade;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Platelet response | Hematological improvement after twelve weeks of eltrombopag treatment | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of platelet response | Duration of platelet response at end of follow-up | 30 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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thrombocytopenia, eltrombopag, Chronic myelomonocytic leukemia