A Study of Eltrombopag in Patients With CMML and Thrombocytopenia

• Status: Completed
• Trial end date: 2021-04-01
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Groupe Francophone des Myelodysplasies
• Collaborators: GlaxoSmithKline; Novartis

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