A Study of Eltrombopag in Patients With CMML and Thrombocytopenia

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

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

Study Overview

• Status: Completed
• Conditions: Thrombocytopenia; CMML
• Intervention / Treatment: Drug: eltrombopag

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Amiens, France, 80054
    • CHU d'Amiens
  • Angers, France, 49 033
    • CHU d'Angers
  • Argenteuil, France, 95107
    • CH Victor Dupouy
  • Bobigny, France, 93009
    • Hôpital Avicenne
  • Cesson-Sévigné, France, 35510
    • Hôpital privé Sévigné
  • Créteil, France, 94010
    • CHU Henri Mondor
  • Grenoble, France, 38043
    • CHU de Grenoble
  • Le Mans, France, 72037
    • CH Le mans
  • Limoges, France, 87046
    • CHRU de Limoges
  • Lyon, France, 69495
    • Centre Hospitalier Lyon Sud
  • Marseille, France, 13009
    • Institut Paoli Calmettes
  • Meaux, France, 77100
    • Centre Hospitalier de Meaux
  • Nantes, France, 44093
    • CHU de Nantes
  • Nantes, France, 44277
    • Centre Catherine de Sienne
  • Nice, France, 06202
    • Hôpital Archet 1
  • Paris, France, 75010
    • Hôpital Saint Louis - Service d'hématologie AJA
  • Paris, France, 75010
    • Hôpital Saint Louis - Service d'hématologie séniors
  • Pessac, France, 33604
    • CHU de Haut-Lévèque
  • Poitiers, France, 86021
    • CHU De Poitiers
  • Pringy cedex, France, 74374
    • Centre hospitalier de la région d'Annecy
  • Rennes, France, 35033
    • Hopital Pontchaillou
  • Rouen, France, 76038
    • Centre Henri Becquerel
  • Toulouse, France, 31059
    • IUCT Oncopole - Médecine interne
  • Toulouse, France, 31059
    • IUCT Oncopole - Service d'Hématologie Clinique
  • Vandoeuvre Les Nancy, France, 54511
    • CHU Brabois
  • Villejuif, France, 94805
    • Institut Gustave Roussy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: eltrombopag	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; Other Names: revolade

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Platelet response	Hematological improvement after twelve weeks of eltrombopag treatment	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of platelet response	Duration of platelet response at end of follow-up	30 months

Other Outcome Measures

Outcome Measure	Time Frame
safety of eltrombopag assessed by clinical and biological toxicity of eltrombopag evaluated using NCI CTCAE v4.0	24 months

Collaborators and Investigators

• Sponsor: Groupe Francophone des Myelodysplasies
• Collaborators: GlaxoSmithKline; Novartis
• Investigators: Principal Investigator: Raphaël Itzykson, MD, Saint-Louis Hospital, Paris, France

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 7, 2014
• Primary Completion (ACTUAL): December 1, 2018
• Study Completion (ACTUAL): April 1, 2021

Study Registration Dates

• First Submitted: May 26, 2014
• First Submitted That Met QC Criteria: December 22, 2014
• First Posted (ESTIMATE): December 23, 2014

Study Record Updates

• Last Update Posted (ACTUAL): April 20, 2021
• Last Update Submitted That Met QC Criteria: April 19, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: eltrombopag; thrombocytopenia; Chronic myelomonocytic leukemia
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Platelet Disorders; Thrombocytopenia
• Other Study ID Numbers: GFM-LMMC-Eltrombopag; 2013-001779-19 (EUDRACT_NUMBER)