A Study of Eltrombopag in Patients With CMML and Thrombocytopenia

Groupe Francophone des Myelodysplasies

Status and phase

Completed

Phase 2

Phase 1

Conditions

CMML

Thrombocytopenia

Treatments

Drug: eltrombopag

Study type

Interventional

Funder types

Other

Industry

Identifiers

GFM-LMMC-Eltrombopag

2013-001779-19 (EudraCT Number)

Details and patient eligibility

About

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

Full description

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

Enrollment

30 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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