Clinical trial NCT03603795: Study Impact on Outcome of Eltrombopag in Elderly Patients with Acute Myeloid Leukemia Receiving Induction Chemotherapy
Official title: A Phase II Randomized Placebo-controlled Study to Assess the Impact on Outcome of Eltrombopag Administered to Elderly Patients with Acute Myeloid Leukemia Receiving Induction Chemotherapy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Lead sponsor: French Innovative Leukemia Organisation
Sponsor class: OTHER
Collaborators: name: Novartis Pharmaceuticals
First posted: 2018-07-27
Enrollment: 110
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomization between 2 arms
Primary purpose: TREATMENT

Brief summary: Phase II randomized placebo-controlled study to assess the impact on outcome of Eltrombopag administered to elderly patients with Acute Myeloid Leukemia (AML) receiving induction chemotherapy. A phase II multicenter and randomized placebo-controlled study

Detailed description: Subjects will be randomized 1:1 to receive Eltrombopag or matching placebo, in double blinded.

To compare overall survival rate at 12 months between the two arms, with or without 200 mg of Eltrombopag daily after induction chemotherapy

Arm A : Eltrombopag 200 mg (100 mg/day for east Asian heritage) once daily from day 11 of induction chemotherapy to AML response evaluation or platelets count \> 100 x 10 Giga/L (maximum day 45)

Arm B : Placebo once daily from day 11 of induction chemotherapy to AML response evaluation or platelets count \> 100 x 10 Giga/L. (maximum day 45)

Eligibility criteria: Inclusion Criteria

* 60 years of age.
* AML de novo, except AML 3 and AML 7.
* AML with no adverse cytogenetic according to Medical Research Council (MRC) 2010 classification.
* Subjects should be eligible for intensive chemotherapy by Daunorubicine, cytarabine, Lomustine.
* Eastern Cooperative Oncology Group (ECOG) \< 3 (appendix 1).
* SORROR ≤ 3 (appendix 2).
* Adequate baseline organ function defined by the criteria below:

  * Total bilirubin ≤ 1.5 x Upper Limit of Normal (ULN) range except cases clearly not indicative of inadequate liver function
  * Alanine Aminotransferase (ALAT) and Aspartate Aminotransferase (ASAT) ≤ 3 x ULN
  * Creatinin ≤ 1.5 x ULN
* Adequate cardiac function with Left Ventricular Ejection fraction (LVEF) ≥50%
* Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
* Women will be menopausal to be enrolled
* The patient must give written (personally signed and dated) informed consent before completing any study-related procedure which means assessment or evaluation that would not form part of the normal medical care of the patient and before the start of induction chemotherapy.
* Affiliated to the French Social Security (Health Insurance).

Exclusion criteria

* Subjects with a diagnosis of acute promyelocytic (M3) or megakaryocytic leukemia (M7).
* AML with adverse cytogenetic according to the MRC 2010 classification.
* AML secondary to Myelodysplastic syndrome (MDS), Myeloproliferative neoplasm (MPN)
* Clinical symptoms suggesting active central nervous system leukemia, or presence of extramedullary AML.
* Previous exposure to anthracycline.
* Previous AML treatment other than hydroxyurea.
* Treatment with an investigational drug within 30 days or 5 half-life whichever is longer, preceding the first dose of study medication.
* History of thromboembolic event or other condition requiring ongoing use of anticoagulation either with warfarin or low molecular-weight heparin.
* History of another malignancy within the past three years except basal cell carcinoma of the skin or carcinoma in situ of the cervix.
* Pre-existing cardiovascular disease (including congestive heart failure, New York Heart Association (NYHA) Grade III/IV), or arrhythmia known to increase the risk of thromboembolic events (e.g. atrial fibrillation), or subjects with a QTc \>450 msec (QTc \>480 msec for subjects with Bundle Branch Block).
* Patient requiring platelets transfusion with platelets \> 10 x 10 Giga/L, for whatever reason.
* History of treatment with romiplostim or other Thrombopoietin receptor (TPO-R) agonists.
* Uncontrolled active infection.
* Any serious medical condition, laboratory abnormality, or psychiatric illness that would place the participant at an unacceptable risk or prevent them from giving informed consent.
* Known active HIV, Hepatitis B or C infection.
* Pregnancy or breastfeeding.

Primary outcomes:
measure: Overal survival rate
timeFrame: 12 months after beginning treatment
Secondary outcomes:
measure: Response rate (CR and CRi) at day 45
timeFrame: At day 45
measure: Leukemia Free Survival at month 12 (one year)
timeFrame: 12 months after beginning treatment
measure: Long-term survival
timeFrame: 2, 3 and 5 years after first treatment administration
measure: Percentage of patients with platelets count > 100 Giga/L at day 45
timeFrame: At day 45
measure: Time to platelet transfusion independence
timeFrame: platelets count daily from baseline to the end of induction (day 45) and then at day 60, day 90, monthly until year 1 and finally at year 2, year 3 and year 5
Other outcomes:
measure: Number of accident haemorrhage events ≥ grade 3
timeFrame: Until day 45
measure: Number of days with platelets count <10 Giga/L
timeFrame: from baseline to the end of induction (day 45) and then at day 60, day 90, monthly until year 1 and finally at year 2, year 3 and year 5
measure: Number of platelets transfusion
timeFrame: from baseline to the end of induction (day 45)
measure: Time to platelets count > 100 Giga/L
timeFrame: from baseline to the end of induction (day 45) and then at day 60, day 90, monthly until year 1 and finally at year 2, year 3 and year 5
measure: Time to peripheral blood polymorphonuclear neutrophils (PMN) counts > 0.5 G/L
timeFrame: from baseline to the end of induction (day 45) and then at day 60, day 90, monthly until year 1 and finally at year 2, year 3 and year 5
measure: Time to haemoglobin counts > 8 g/dl
timeFrame: from baseline to the end of induction (day 45) and then at day 60, day 90, monthly until year 1 and finally at year 2, year 3 and year 5
measure: Time to red blood cells transfusion independence
timeFrame: from baseline to the end of induction (day 45) and then at day 60, day 90, monthly until year 1 and finally at year 2, year 3 and year 5
measure: Eltrombopag-Emergent Adverse Events
timeFrame: Until day 90
measure: Evaluation of quality of life
timeFrame: At baseline and at the end of induction (maximum up to day 45)
Locations:
city: Angers
country: France
facility: CHU ANGERS - Maladies du sang
city: Bayonne
country: France
facility: CH de la Côte Basque - Hématologie
city: Clermont-Ferrand
country: France
facility: CHU Estaing
city: Grenoble
country: France
facility: CHU Grenoble - Hématologie Clinique
city: Marseille
country: France
facility: Institut Paoli-Calmettes - Hématologie 2
city: Montpellier
country: France
facility: Hôpital Saint-Eloi - Hématologie Clinique
city: Mulhouse
country: France
facility: HOPITAL E. MULLER - Hématologie
city: Nantes
country: France
facility: CHU HOTEL DIEU - Hématologie Clinique
city: Nîmes
country: France
facility: CHU Caremeau
city: Poitiers
country: France
facility: CHU La Milétrie - Hématologie Clinique
city: Rennes
country: France
facility: CHU Pontchaillou
city: Strasbourg
country: France
facility: CHU Hautepierre - Hématologie
city: Toulouse
country: France
facility: Institut Universitaire du Cancer de Toulouse Oncopole - Service d'Hématologie
city: Tours
country: France
facility: Sponsor FILO
city: Vandœuvre-lès-Nancy
country: France
facility: CHU de Brabois
Study officials:
affiliation: French Innovative Leukemia Organization (FILO)
name: Arnaud PIGNEUX, MD PD
role: PRINCIPAL_INVESTIGATOR
References: