Acute Myeloid Leukemia
Conditions
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)
Interventions
DRUGEltrombopag
Eltrombopag concomitant with induction chemotherapy in patient with AML
DRUGPlacebo
Placebo concomitant with induction chemotherapy patients with AML
Sponsors
Novartis Pharmaceuticals
French Innovative Leukemia Organisation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
Randomization between 2 arms
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overal survival rate | 12 months after beginning treatment | overall survival rate at month 12 (year 1) between the two arms, with or without 200 mg of Eltrombopag daily after induction chemotherapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response rate (CR and CRi) at day 45 | At day 45 | — |
| Leukemia Free Survival at month 12 (one year) | 12 months after beginning treatment | relapse measurement before month 12 |
| Long-term survival | 2, 3 and 5 years after first treatment administration | Overall survival at 2, 3 and 5 years |
| Percentage of patients with platelets count > 100 Giga/L at day 45 | At day 45 | platelets count \>100 Giga/L |
| 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 | More than 3 days with platelets count ≥ 10 Giga/L |
Other
| Measure | Time frame | Description |
|---|---|---|
| Time to red blood cells transfusion independence | 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 | Daily measurement of Red blood cells count and transfusion monitoring |
| Number of accident haemorrhage events ≥ grade 3 | Until day 45 | All accident haemorrhage event ≥ grade 3 |
| Evaluation of quality of life | At baseline and at the end of induction (maximum up to day 45) | 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. |
| Eltrombopag-Emergent Adverse Events | Until day 90 | Incidence and severity of Eltrombopag-Emergent Adverse Events utilizing National Cancer Institute - Common Terminology Criteria (NCI-CTC) criteria v4.03 |
| 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 | Daily measurement of platelets count |
| Number of platelets transfusion | from baseline to the end of induction (day 45) | — |
| Time to platelets count > 100 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 | Daily measurement of platelets count |
| Time to peripheral blood polymorphonuclear neutrophils (PMN) counts > 0.5 G/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 | Daily measurement of peripheral blood PMN count |
| Time to haemoglobin counts > 8 g/dl | 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 | Daily measurement of haemoglobin count |
Countries
France
Outcome results
None listed