A Study of Eltrombopag in Patients With CMML and Thrombocytopenia

Phase 1

Completed

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
eltrombopag	eltrombopag	-

Primary Outcome Measures

Name	Time	Method
Platelet response	12 weeks	Hematological improvement after twelve weeks of eltrombopag treatment

Secondary Outcome Measures

Name	Time	Method
Duration of platelet response	30 months	Duration of platelet response at end of follow-up

Locations (26): CHU d'Angers
🇫🇷
Angers, France
Hôpital privé Sévigné
🇫🇷
Cesson-Sévigné, France
Centre Hospitalier de Meaux
🇫🇷
Meaux, France
Centre Catherine de Sienne
🇫🇷
Nantes, France
CHU de Haut-Lévèque
🇫🇷
Pessac, France
Centre Henri Becquerel
🇫🇷
Rouen, France
CH Victor Dupouy
🇫🇷
Argenteuil, France
Hôpital Avicenne
🇫🇷
Bobigny, France
CHU Henri Mondor
🇫🇷
Créteil, France
CHRU de Limoges
🇫🇷
Limoges, France
CHU de Grenoble
🇫🇷
Grenoble, France
CH Le Mans
🇫🇷
Le Mans, France
Institut Paoli Calmettes
🇫🇷
Marseille, France
CHU de Nantes
🇫🇷
Nantes, France
Hôpital Archet 1
🇫🇷
Nice, France
Hôpital Saint Louis - Service d'hématologie AJA
🇫🇷
Paris, France
Hôpital Saint Louis - Service d'hématologie séniors
🇫🇷
Paris, France
CHU de Poitiers
🇫🇷
Poitiers, France
Centre Hospitalier de la région d'Annecy
🇫🇷
Pringy cedex, France
Hôpital Pontchaillou
🇫🇷
Rennes, France
IUCT Oncopole - Médecine interne
🇫🇷
Toulouse, France
IUCT Oncopole - Service d'Hématologie Clinique
🇫🇷
Toulouse, France
CHU Brabois
🇫🇷
Vandoeuvre Les Nancy, France
Institut Gustave Roussy
🇫🇷
Villejuif, France
Centre Hospitalier Lyon Sud
🇫🇷
Lyon, France
CHU d'Amiens
🇫🇷
Amiens, France