A Study of Eltrombopag in Patients With CMML and Thrombocytopenia

Thrombocytopenia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02323178
• Other study ID #: GFM-LMMC-Eltrombopag
• Secondary ID: 2013-001779-19
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: August 7, 2014
• Est. completion date: April 2021

Study information

• Verified date: April 2021
• Source: Groupe Francophone des Myelodysplasies
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: April 2021
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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

Related Conditions & MeSH terms

• CMML
• Thrombocytopenia

Intervention

Drug:
• eltrombopag
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

Locations

Country	Name	City	State
France	CHU d'Amiens	Amiens
France	CHU d'Angers	Angers
France	CH Victor Dupouy	Argenteuil
France	Hôpital Avicenne	Bobigny
France	Hôpital privé Sévigné	Cesson-Sévigné
France	CHU Henri Mondor	Créteil
France	CHU de Grenoble	Grenoble
France	CH Le Mans	Le Mans
France	CHRU de Limoges	Limoges
France	Centre Hospitalier Lyon Sud	Lyon
France	Institut Paoli Calmettes	Marseille
France	Centre Hospitalier de Meaux	Meaux
France	Centre Catherine de Sienne	Nantes
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 Haut-Lévèque	Pessac
France	CHU de Poitiers	Poitiers
France	Centre Hospitalier de la région d'Annecy	Pringy cedex
France	Hôpital Pontchaillou	Rennes
France	Centre Henri Becquerel	Rouen
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

Sponsors (3)

Lead Sponsor	Collaborator
Groupe Francophone des Myelodysplasies	GlaxoSmithKline, Novartis

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	safety of eltrombopag assessed by clinical and biological toxicity of eltrombopag evaluated using NCI CTCAE v4.0		24 months
Primary	Platelet response	Hematological improvement after twelve weeks of eltrombopag treatment	12 weeks
Secondary	Duration of platelet response	Duration of platelet response at end of follow-up	30 months