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Study Impact on Outcome of Eltrombopag in Elderly Patients With Acute Myeloid Leukemia Receiving Induction Chemotherapy (EPAG2015)

Primary Purpose

Acute Myeloid Leukemia

Status
Active
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Eltrombopag
Placebo
Sponsored by
French Innovative Leukemia Organisation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia

Eligibility Criteria

60 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • CHU ANGERS - Maladies du sang
  • CH de la Côte Basque - Hématologie
  • CHU Estaing
  • CHU Grenoble - Hématologie Clinique
  • Institut Paoli-Calmettes - Hématologie 2
  • Hôpital Saint-Eloi - Hématologie Clinique
  • HOPITAL E. MULLER - Hématologie
  • CHU HOTEL DIEU - Hématologie Clinique
  • CHU Caremeau
  • CHU La Milétrie - Hématologie Clinique
  • CHU Pontchaillou
  • CHU Hautepierre - Hématologie
  • Institut Universitaire du Cancer de Toulouse Oncopole - Service d'Hématologie
  • Sponsor FILO
  • CHU de Brabois

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

A

B

Arm Description

55 patients will be randomized in the experimental arm A. If platelets counts < 100 x 10 Giga/L, patients will be treated with Eltrombopag 200 mg/day per os from day 11 of induction chemotherapy to platelets counts > 100 x 10 Giga/L or maximum to day 45. If platelets counts ≥ 100 x 10 Giga/L on day 11, the start of IP will be delayed until platelets < 100 x 10 Giga/L. Chemotherapy administration would be performed among standard practice: Daunorubicin: 60 mg/m² D1 to D3 Cytarabine: 100 mg/m²/day, in a continuous 24h-IV infusion D1 to D7 Lomustine (CCNU): 200 mg/m² per os, at D1. 200mg = 4 Tablets of 50 mg will be done more than 2 hours before Daunorubicin and cytarabine administrations, to avoid vomiting secondary to anthracycline administration. Investigational Product (IP) will be taken at the same time daily on an empty stomach 1 hour before or 2 hours after a meal or preferably no calcium or dairy products.

55 patients will be randomized in the comparator arm B and will received: Placebo once daily from day 11 of induction chemotherapy to AML response evaluation or platelets count > 100 x 10 Giga/L (maximum day 45) Placebo 200mg = 4 Tablets of 50 mg will be done more than 2 hours before Daunorubicin and cytarabine administrations, to avoid vomiting secondary to anthracycline administration. Chemotherapy administration would be performed among standard practice: Daunorubicin: 60 mg/m² D1 to D3 Cytarabine: 100 mg/m²/day, in a continuous 24h-IV infusion D1 to D7 Lomustine (CCNU): 200 mg/m² per os, at D1.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Response rate (CR and CRi) at day 45
Leukemia Free Survival at month 12 (one year)
relapse measurement before month 12
Long-term survival
Overall survival at 2, 3 and 5 years
Percentage of patients with platelets count > 100 Giga/L at day 45
platelets count >100 Giga/L
Time to platelet transfusion independence
More than 3 days with platelets count ≥ 10 Giga/L

Full Information

First Posted
April 20, 2018
Last Updated
September 23, 2022
Sponsor
French Innovative Leukemia Organisation
Collaborators
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT03603795
Brief Title
Study Impact on Outcome of Eltrombopag in Elderly Patients With Acute Myeloid Leukemia Receiving Induction Chemotherapy
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 11, 2018 (Actual)
Primary Completion Date
June 15, 2022 (Actual)
Study Completion Date
September 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
French Innovative Leukemia Organisation
Collaborators
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Randomization between 2 arms
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
110 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
A
Arm Type
Experimental
Arm Description
55 patients will be randomized in the experimental arm A. If platelets counts < 100 x 10 Giga/L, patients will be treated with Eltrombopag 200 mg/day per os from day 11 of induction chemotherapy to platelets counts > 100 x 10 Giga/L or maximum to day 45. If platelets counts ≥ 100 x 10 Giga/L on day 11, the start of IP will be delayed until platelets < 100 x 10 Giga/L. Chemotherapy administration would be performed among standard practice: Daunorubicin: 60 mg/m² D1 to D3 Cytarabine: 100 mg/m²/day, in a continuous 24h-IV infusion D1 to D7 Lomustine (CCNU): 200 mg/m² per os, at D1. 200mg = 4 Tablets of 50 mg will be done more than 2 hours before Daunorubicin and cytarabine administrations, to avoid vomiting secondary to anthracycline administration. Investigational Product (IP) will be taken at the same time daily on an empty stomach 1 hour before or 2 hours after a meal or preferably no calcium or dairy products.
Arm Title
B
Arm Type
Placebo Comparator
Arm Description
55 patients will be randomized in the comparator arm B and will received: Placebo once daily from day 11 of induction chemotherapy to AML response evaluation or platelets count > 100 x 10 Giga/L (maximum day 45) Placebo 200mg = 4 Tablets of 50 mg will be done more than 2 hours before Daunorubicin and cytarabine administrations, to avoid vomiting secondary to anthracycline administration. Chemotherapy administration would be performed among standard practice: Daunorubicin: 60 mg/m² D1 to D3 Cytarabine: 100 mg/m²/day, in a continuous 24h-IV infusion D1 to D7 Lomustine (CCNU): 200 mg/m² per os, at D1.
Intervention Type
Drug
Intervention Name(s)
Eltrombopag
Other Intervention Name(s)
Arm Eltrombopag, Arm experimental A
Intervention Description
Eltrombopag concomitant with induction chemotherapy in patient with AML
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Arm placebo, Arm B
Intervention Description
Placebo concomitant with induction chemotherapy patients with AML
Primary Outcome Measure Information:
Title
Overal survival rate
Description
overall survival rate at month 12 (year 1) between the two arms, with or without 200 mg of Eltrombopag daily after induction chemotherapy.
Time Frame
12 months after beginning treatment
Secondary Outcome Measure Information:
Title
Response rate (CR and CRi) at day 45
Time Frame
At day 45
Title
Leukemia Free Survival at month 12 (one year)
Description
relapse measurement before month 12
Time Frame
12 months after beginning treatment
Title
Long-term survival
Description
Overall survival at 2, 3 and 5 years
Time Frame
2, 3 and 5 years after first treatment administration
Title
Percentage of patients with platelets count > 100 Giga/L at day 45
Description
platelets count >100 Giga/L
Time Frame
At day 45
Title
Time to platelet transfusion independence
Description
More than 3 days with platelets count ≥ 10 Giga/L
Time Frame
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 Pre-specified Outcome Measures:
Title
Number of accident haemorrhage events ≥ grade 3
Description
All accident haemorrhage event ≥ grade 3
Time Frame
Until day 45
Title
Number of days with platelets count <10 Giga/L
Description
Daily measurement of platelets count
Time Frame
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
Title
Number of platelets transfusion
Time Frame
from baseline to the end of induction (day 45)
Title
Time to platelets count > 100 Giga/L
Description
Daily measurement of platelets count
Time Frame
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
Title
Time to peripheral blood polymorphonuclear neutrophils (PMN) counts > 0.5 G/L
Description
Daily measurement of peripheral blood PMN count
Time Frame
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
Title
Time to haemoglobin counts > 8 g/dl
Description
Daily measurement of haemoglobin count
Time Frame
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
Title
Time to red blood cells transfusion independence
Description
Daily measurement of Red blood cells count and transfusion monitoring
Time Frame
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
Title
Eltrombopag-Emergent Adverse Events
Description
Incidence and severity of Eltrombopag-Emergent Adverse Events utilizing National Cancer Institute - Common Terminology Criteria (NCI-CTC) criteria v4.03
Time Frame
Until day 90
Title
Evaluation of quality of life
Description
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.
Time Frame
At baseline and at the end of induction (maximum up to day 45)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Arnaud PIGNEUX, MD PD
Organizational Affiliation
French Innovative Leukemia Organization (FILO)
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU ANGERS - Maladies du sang
City
Angers
ZIP/Postal Code
49933
Country
France
Facility Name
CH de la Côte Basque - Hématologie
City
Bayonne
ZIP/Postal Code
64109
Country
France
Facility Name
CHU Estaing
City
Clermont-Ferrand
ZIP/Postal Code
63003
Country
France
Facility Name
CHU Grenoble - Hématologie Clinique
City
Grenoble
ZIP/Postal Code
38043
Country
France
Facility Name
Institut Paoli-Calmettes - Hématologie 2
City
Marseille
ZIP/Postal Code
13000
Country
France
Facility Name
Hôpital Saint-Eloi - Hématologie Clinique
City
Montpellier
ZIP/Postal Code
34295
Country
France
Facility Name
HOPITAL E. MULLER - Hématologie
City
Mulhouse
ZIP/Postal Code
68070
Country
France
Facility Name
CHU HOTEL DIEU - Hématologie Clinique
City
Nantes
ZIP/Postal Code
44093
Country
France
Facility Name
CHU Caremeau
City
Nîmes
ZIP/Postal Code
30029
Country
France
Facility Name
CHU La Milétrie - Hématologie Clinique
City
Poitiers
ZIP/Postal Code
86000
Country
France
Facility Name
CHU Pontchaillou
City
Rennes
ZIP/Postal Code
35033
Country
France
Facility Name
CHU Hautepierre - Hématologie
City
Strasbourg
ZIP/Postal Code
67098
Country
France
Facility Name
Institut Universitaire du Cancer de Toulouse Oncopole - Service d'Hématologie
City
Toulouse
ZIP/Postal Code
31059
Country
France
Facility Name
Sponsor FILO
City
Tours
ZIP/Postal Code
37044
Country
France
Facility Name
CHU de Brabois
City
Vandœuvre-lès-Nancy
ZIP/Postal Code
54500
Country
France

12. IPD Sharing Statement

Links:
URL
http://www.filo-leucemie.org
Description
FILO internet site

Learn more about this trial

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

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