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

NCT03603795 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: EPAG 2015
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 15

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

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Response rate (CR and CRi) at day 45

  At day 45

• Leukemia Free Survival at month 12 (one year)

  12 months after beginning treatment

• Long-term survival

  2, 3 and 5 years after first treatment administration

• Percentage of patients with platelets count > 100 Giga/L at day 45

  At day 45

• Time to platelet transfusion independence

  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 (9)

• Number of accident haemorrhage events ≥ grade 3

  Until day 45

• Number of days with platelets count <10 Giga/L

  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

• Number of platelets transfusion

  from baseline to the end of induction (day 45)

Study Arms (2)

A

EXPERIMENTAL

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.

Drug: Eltrombopag

B

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Eltrombopag DRUG

Eltrombopag concomitant with induction chemotherapy in patient with AML

Also known as: Arm Eltrombopag, Arm experimental A

A

Placebo DRUG

Placebo concomitant with induction chemotherapy patients with AML

Also known as: Arm placebo, Arm B

B

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• French Innovative Leukemia Organisation: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (15)

CHU ANGERS - Maladies du sang

Angers, 49933, France

Location

CH de la Côte Basque - Hématologie

Bayonne, 64109, France

Location

CHU Estaing

Clermont-Ferrand, 63003, France

Location

CHU Grenoble - Hématologie Clinique

Grenoble, 38043, France

Location

Institut Paoli-Calmettes - Hématologie 2

Marseille, 13000, France

Location

Hôpital Saint-Eloi - Hématologie Clinique

Montpellier, 34295, France

Location

HOPITAL E. MULLER - Hématologie

Mulhouse, 68070, France

Location

CHU HOTEL DIEU - Hématologie Clinique

Nantes, 44093, France

Location

CHU Caremeau

Nîmes, 30029, France

Location

CHU La Milétrie - Hématologie Clinique

Poitiers, 86000, France

Location

CHU Pontchaillou

Rennes, 35033, France

Location

CHU Hautepierre - Hématologie

Strasbourg, 67098, France

Location

Institut Universitaire du Cancer de Toulouse Oncopole - Service d'Hématologie

Toulouse, 31059, France

Location

Sponsor FILO

Tours, 37044, France

Location

CHU de Brabois

Vandœuvre-lès-Nancy, 54500, France

Location

Related Links

• FILO internet site

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

eltrombopag

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Arnaud PIGNEUX, MD PD

  French Innovative Leukemia Organization (FILO)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomization between 2 arms

Study Record Dates

• First Submitted: April 20, 2018
• First Posted: July 27, 2018
• Study Start: October 11, 2018
• Primary Completion: June 15, 2022
• Study Completion (Estimated): July 30, 2026
• Last Updated: October 29, 2024

Record last verified: 2024-10

Locations

FR (15)