Clinical trial NCT02323178: A Study of Eltrombopag in Patients With CMML and Thrombocytopenia
Official title: A Phase I/II Study of Eltrombopag in Patients With Chronic Myelomonocytic Leukemia and Thrombocytopenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: CMML
Thrombocytopenia
Keywords: Chronic myelomonocytic leukemia
thrombocytopenia
eltrombopag
Lead sponsor: Groupe Francophone des Myelodysplasies
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
name: Novartis
First posted: 2014-12-23
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Platelet response
timeFrame: 12 weeks
Secondary outcomes:
measure: Duration of platelet response
timeFrame: 30 months
Other outcomes:
measure: safety of eltrombopag assessed by clinical and biological toxicity of eltrombopag evaluated using NCI CTCAE v4.0
timeFrame: 24 months
Locations:
city: Amiens
country: France
facility: CHU d'Amiens
city: Angers
country: France
facility: CHU d'Angers
city: Argenteuil
country: France
facility: CH Victor Dupouy
city: Bobigny
country: France
facility: Hôpital Avicenne
city: Cesson-Sévigné
country: France
facility: Hôpital privé Sévigné
city: Créteil
country: France
facility: CHU Henri Mondor
city: Grenoble
country: France
facility: CHU de Grenoble
city: Le Mans
country: France
facility: CH Le Mans
city: Limoges
country: France
facility: CHRU de Limoges
city: Lyon
country: France
facility: Centre Hospitalier Lyon Sud
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Meaux
country: France
facility: Centre Hospitalier de Meaux
city: Nantes
country: France
facility: CHU de Nantes
city: Nantes
country: France
facility: Centre Catherine de Sienne
city: Nice
country: France
facility: Hôpital Archet 1
city: Paris
country: France
facility: Hôpital Saint Louis - Service d'hématologie AJA
city: Paris
country: France
facility: Hôpital Saint Louis - Service d'hématologie séniors
city: Pessac
country: France
facility: CHU de Haut-Lévèque
city: Poitiers
country: France
facility: CHU de Poitiers
city: Pringy cedex
country: France
facility: Centre Hospitalier de la région d'Annecy
city: Rennes
country: France
facility: Hôpital Pontchaillou
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Toulouse
country: France
facility: IUCT Oncopole - Médecine interne
city: Toulouse
country: France
facility: IUCT Oncopole - Service d'Hématologie Clinique
city: Vandoeuvre Les Nancy
country: France
facility: CHU Brabois
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: Saint-Louis Hospital, Paris, France
name: Raphaël Itzykson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Saint-Louis Hospital, Paris, France
name: Pierre Fenaux, MD, PHD
role: STUDY_DIRECTOR
References: