Study Impact on Outcome of Eltrombopag in Elderly Patients With Acute Myeloid Leukemia Receiving Induction Chemotherapy

Acute Myeloid Leukemia Clinical Trial

— EPAG2015  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03603795
• Other study ID #: EPAG 2015
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 11, 2018
• Est. completion date: September 2024

Study information

• Verified date: September 2022
• Source: French Innovative Leukemia Organisation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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)

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 110
• Est. completion date: September 2024
• Est. primary completion date: June 15, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Eltrombopag
Eltrombopag concomitant with induction chemotherapy in patient with AML
• Placebo
Placebo concomitant with induction chemotherapy patients with AML

Locations

Country	Name	City	State
France	CHU ANGERS - Maladies du sang	Angers
France	CH de la Côte Basque - Hématologie	Bayonne
France	CHU Estaing	Clermont-Ferrand
France	CHU Grenoble - Hématologie Clinique	Grenoble
France	Institut Paoli-Calmettes - Hématologie 2	Marseille
France	Hôpital Saint-Eloi - Hématologie Clinique	Montpellier
France	HOPITAL E. MULLER - Hématologie	Mulhouse
France	CHU HOTEL DIEU - Hématologie Clinique	Nantes
France	CHU Caremeau	Nîmes
France	CHU La Milétrie - Hématologie Clinique	Poitiers
France	CHU Pontchaillou	Rennes
France	CHU Hautepierre - Hématologie	Strasbourg
France	Institut Universitaire du Cancer de Toulouse Oncopole - Service d'Hématologie	Toulouse
France	Sponsor FILO	Tours
France	CHU de Brabois	Vandœuvre-lès-Nancy

Sponsors (2)

Lead Sponsor	Collaborator
French Innovative Leukemia Organisation	Novartis Pharmaceuticals

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of accident haemorrhage events = grade 3	All accident haemorrhage event = grade 3	Until day 45
Other	Number of days with platelets count <10 Giga/L	Daily measurement of platelets count	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	Number of platelets transfusion		from baseline to the end of induction (day 45)
Other	Time to platelets count > 100 Giga/L	Daily measurement of platelets count	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	Time to peripheral blood polymorphonuclear neutrophils (PMN) counts > 0.5 G/L	Daily measurement of peripheral blood PMN count	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	Time to haemoglobin counts > 8 g/dl	Daily measurement of haemoglobin count	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	Time to red blood cells transfusion independence	Daily measurement of Red blood cells count and transfusion monitoring	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	Eltrombopag-Emergent Adverse Events	Incidence and severity of Eltrombopag-Emergent Adverse Events utilizing National Cancer Institute - Common Terminology Criteria (NCI-CTC) criteria v4.03	Until day 90
Other	Evaluation of quality of life	EORTC Quality of Life Questionnaire - Core Questionnaire (QLQ-C30). The QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items.; Each of the multi-item scales includes a different set of items - no item occurs in more than one scale.; All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.	At baseline and at the end of induction (maximum up to day 45)
Primary	Overal survival rate	overall survival rate at month 12 (year 1) between the two arms, with or without 200 mg of Eltrombopag daily after induction chemotherapy.	12 months after beginning treatment
Secondary	Response rate (CR and CRi) at day 45		At day 45
Secondary	Leukemia Free Survival at month 12 (one year)	relapse measurement before month 12	12 months after beginning treatment
Secondary	Long-term survival	Overall survival at 2, 3 and 5 years	2, 3 and 5 years after first treatment administration
Secondary	Percentage of patients with platelets count > 100 Giga/L at day 45	platelets count >100 Giga/L	At day 45
Secondary	Time to platelet transfusion independence	More than 3 days with platelets count = 10 Giga/L	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

External Links

•   FILO internet site