elderly patients (> = 60 years) with Acute Myeloid Leukemia MedDRA version: 21.1 Level: PT Classification code 10000880 Term: Acute myeloid leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Sponsors
FILO
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Principal inclusion criteria (pre-induction) : - = 60 years of age. - AML de novo according to the WHO 2016 classification - AML with favorable or intermediate cytogenetic risk according to ELN 2017 - Subjects should be eligible for intensive chemotherapy by Idarubicin, Cytarabine and Lomustine (standard induction for FILO) - SORROR =65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: Principal exclusion criteria (at diagnosis, before induction) : - Diagnosis of APL - AML with adverse cytogenetics according to ELN 2017 - AML with BCR-ABL1 translocation - Subject with an antecedent of myeloproliferative neoplasm (MPN) including myelofibrosis, essential thrombocytosis, polycythemia vera or chronic myelogenous leukemia (CML) with or without BCR-ABL1 translocation - Clinical symptoms suggesting active central nervous system leukemia, or presence of isolated extramedullary leukemia - Previous exposure to Anthracycline = 550mg/m² (Daunorubicin equivalence) - Previous AML treatment other than Hydroxyurea - Treatment with an investigational drug within 30 days or 5 half-life whichever is longer, preceding the initiation study and/or previous treatment with Venetoclax - History of another malignancy within the past 3 years except basal cell carcinoma of the skin or cervix in situ carcinoma - Any serious medical condition, laboratory abnormalities or psychiatric illness that would place the participant at an unacceptable risk or prevent them from giving informed consent or precluding the administration of protocol treatments - Other comorbidity that the physician judges to be incompatible with conventional intensive chemotherapy which must be reviewed and approved by the study medical monitor before study enrolment 12. Subject with known HIV infection (due to potential drug-drug interactions between antiretroviral medications and Venetoclax).. Subject known to be positive for hepatitis B virus (HBV) or hepatitis C virus (HCV) infection; Inactive hepatitis carrier status with undetectable PCR viral load on antivirals (non-exclusionary medications) are not excluded Principal non-randomization criteria (after induction phase) : - Patient in PR, or failure to follow one induction course by Idarubicin, Cytarabine and Lomustine, according to ELN 2017 criteria - Uncontrolled infection - Subject with cardiovascular disability status as per the New York Heart Association Class > 2. - Subject has a malabsorption syndrome or other condition that precludes enteral route of administration - 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 - Treatment with any of the following within 7 days prior to the first dose of study drug : a. Strong or moderate CYP3A inducers b. Steroid therapy for anti-neoplastic intent - Subject having consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Star fruit within 3 days prior to the initiation of study treatment - Subject having chronic respiratory disease that requires continuous oxygen, or a significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, any other medical condition that in the opinion of the investigator would adversely affect his/her participating in this study - Previous treatment with Venetoclax and/or current participation in any other research study with investigational products - Known hypersensitivity to the study medication
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the Relapse free survival (RFS) at 2 years after follow-up between the two arms: Venetoclax with Cytarabine versus Idarubicin with Cytarabine. ;Secondary Objective: -Overall survival (OS) at 2 years - Event Free Survival (EFS) at 2 years -Cumulative incidence of relapse and death in first remission -Impact of treatment on measurable minimal residual disease (MRD) -Toxicity of Venetoclax in combination with Cytarabine according to NCI-CTCAE v5.0 -Death rate during consolidation -Impact of Venetoclax in allografted patients and in non-allografted patients -Evaluation of quality of life using the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) questionnaire -Adverse events reported according to the descriptions and grading scale found in version 5.0 of the NCI-CTCAE. ;Primary end point(s): Relapse free survival (RFS) at 2 years according to ELN 2017 criteria;Timepoint(s) of evaluation of this end point: at 2 years post-treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Overall survival (OS) at 2 years - Event Free Survival (EFS) at 2 years - Cumulative incidence of relapse and death in first remission - Impact of treatment on measurable minimal residual disease (MRD) - Toxicity of Venetoclax in combination with Cytarabine according to NCI-CTC criteria v5.0 - Death rate during consolidation - Impact of Venetoclax in allografted patients and in non-allografted patients - Evaluation of quality of life using the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) questionnaire - Adverse events reported according to the descriptions and grading scale found in version 5.0 of the NCI-CTCAE. ;Timepoint(s) of evaluation of this end point: at the end of study | — |
Countries
France
Contacts
Public ContactFENOLL Cindy
FILO
Outcome results
None listed