CMML, Thrombocytopenia
Conditions
Keywords
Chronic myelomonocytic leukemia, thrombocytopenia, eltrombopag
Brief summary
Treatment of patients with chronic myelomonocytic leukemia (CMML) and thrombocytopenia.
Detailed description
All eligible patients will be treated with eltrombopag for a minimum of twelve weeks and a maximum of 24 months.
Interventions
DRUGeltrombopag
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
Sponsors
GlaxoSmithKline
Novartis
Groupe Francophone des Myelodysplasies
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Platelet response | 12 weeks | Hematological improvement after twelve weeks of eltrombopag treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of platelet response | 30 months | Duration of platelet response at end of follow-up |
Other
| Measure | Time frame |
|---|---|
| safety of eltrombopag assessed by clinical and biological toxicity of eltrombopag evaluated using NCI CTCAE v4.0 | 24 months |
Countries
France
Outcome results
None listed