Ireland
--:--IST
Active, not recruiting Phase 2

Venetoclax + Cytarabine Versus Idarubicin + Cytarabine : Efficacity Assessment as Post-remission Therapy to Elderly Patients With Acute Myeloid Leukemia in First Remission

NCT04968015 · tracked via the Priya Life Science France tracker
Phase
Phase 2
Started
2022-05-25
Last updated
2024-06-27

Condition(s) studied

Acute Myeloid Leukemia

Investigational drug(s) / intervention(s)

Cytarabine-Venetoclax AssociationCytarabine-Idarubicin Association

Cytarabine-Venetoclax Association: Consolidation treatment with cytarabine + venetoclax

Cytarabine-Idarubicin Association: Consolidation treatment with cytarabine + idarubicin

Study summary

For the FILO group, the standard of care for induction chemotherapy of elderly fit patients with AML is represented by the combination of Cytarabine, Idarubicin and Lomustine. The superiority of this combination was confirmed in a larger prospective study the LAMSA-2007. This induction treatment, followed by six courses of consolidation (Idarubicin and Cytarabine) followed then by a period of 6-month maintenance therapy, allows up to 80 % of remission, and a RFS of 46 % at 2 years.

The aim of the study is to assess the efficacy on outcome of Venetoclax combined with Cytarabine versus Idarubicin combined with Cytarabine administered as post-remission therapy to elderly patients with acute myeloid leukemia in first complete remission (CR) following induction chemotherapy.

Eligibility

Sex
ALL
Min age
60 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria : * ≥ 60 years of age. * AML de novo according to the WHO 2016 classification * AML with favorable or intermediate cytogenetics according to ELN 2017 * Subjects should be eligible for intensive chemotherapy by Idarubicin, Cytarabine, and Lomustine (standard induction for FILO) * SORROR \< 3 (for the protocol, calculation of Sorror excludes a history of cancer) (appendix 2) * AML secondary to MDS or chemotherapy are eligible, unless adverse cytogenetics * Eastern Cooperative Oncology Group (ECOG) \< 3 (appendix 1) * Adequate baseline organ function defined by the criteria below: * Adequate renal function as demonstrated by a creatinine clearance ≥ 50 mL/min; calculated by the Cockcroft Gault formula or measured by 24-hours urine collection * Aspartate aminotransferase (AST) ≤ 3.0 × upper limit of normal (ULN) * Alanine aminotransferase (ALT) ≤ 3.0 × ULN * Bilirubin ≤ 1.5 × ULN * Adequate cardiac function with Left Ventricular Ejection Fraction (LVEF) ≥ 50 % * Absence of any psychological, familial, sociological or geographical conditions potentially hampering compliance with the study protocol and follow-up schedule * Females must be menopausal to be pre-enrolled * Patients must be affiliated to the French Social Security (health insurance) * Signed written informed consent for the study Exclusion Criteria: * Diagnosis of Acute Promyelocytic Leukemia (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 of anthracycline ≥ 550 mg/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 * Subject with known HIV infection (due to potential drug-drug interactions between antiretroviral medications and Venetoclax). HIV testing will be performed at Screening. Subject known to be positive for hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Inactive hepatitis carrier status with undetectable Polymerase Chain Reaction (PCR) viral load on antivirals (non-exclusionary medications) are not excluded. Randomization criteria: 1. Subjects must have been registered at diagnosis 2. Subjects must have received intensive induction by Idarubicin, Cytarabine and Lomustine 3. Patients in Complete Response / Complete Response with incomplete hematologic recovery (CR/CRi) post induction according to ELN 2017 criteria 4. Randomization should be performed no more than D+60 after induction 5. ECOG \< 3 (appendix 1) 6. Adequate baseline organ function defined by the criteria below: * Adequate renal function as demonstrated by a creatinine clearance ≥ 50 mL/min; calculated by the Cockcroft Gault formula or measured by 24-hours urine collection * Aspartate aminotransferase (AST) ≤ 3.0 × ULN * Alanine aminotransferase (ALT) ≤ 3.0 × ULN * Bilirubin ≤ 1.5 × ULN 7. Adequate cardiac function with LVEF ≥ 50 % 8. Male subjects who are sexually active must agree, from study Day 1 through at least 180 days after the last dose of study drug, to practice protocol-specified methods of contraception 9. Female subjects must be postmenopausal defined as with no menses for 12 or more months without an alternative medical cause Non randomization criteria 1. Patient in Partial Remission (PR) or failure following one induction course by Idarubicin, Cytarabine and Lomustine (according ELN 2017 criteria) 2. Uncontrolled infection 3. Subject with cardiovascular disability status as per New York Heart Association Class \> 2. Class 2 is defined as cardiac disease in which subjects are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea, or angina pain. Class 3 is defined as cardiac disease in which subjects are comfortable at rest but less than ordinary activity causes fatigue, palpitation, or dyspnea. Class 4 is defined as cardiac disease in which subjects have an inability to carry on any physical activity without discomfort, symptoms of heart failure at rest, and if any physical activity is undertaken then discomfort increases. 4. Subject has a malabsorption syndrome or other condition that precludes enteral route of administration. 5. 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. 6. Treatment with any of the following within 7 days prior to the first dose of study drug : * Strong or moderate CYP3A inducers * Steroid therapy for anti-neoplastic intent 7. 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. 8. 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. 9. Previous treatment with Venetoclax and/or current participation in any other research study with investigational products. 10. Known hypersensitivity to the study medication

Primary outcome measure(s)

  • Relapse Free Survival (RFS) — from randomization to last follow-up (up to 5 years)
    RFS measured from the date of achievement of a remission until the date of relapse or death from any cause

Trial sites (26)

FacilityCityRegionStatus
ANGERS - CHU - Maladies du sang Angers France
ANNECY - Centre Hospitalier Annecy-Genevois Annecy France
AVIGNON - Centre Hospitalier Avignon France
BAYONNE - CH de la Côte Basque - Hématologie Bayonne France
BESANCON - Hôpital Jean Minjoz - Hématologie Besançon France
BEZIERS - Centre Hospitalier - Hématologie Béziers France
Clermont-Ferrand - Chu Estaing Clermont-Ferrand France
Grenoble - CHUGA - Hématologie Clinique Grenoble France
LYON-Centre Léon Bérard Lyon France
MARSEILLE - Institut Paoli-Calmettes Marseille France
METZ - CHR Metz-Thionville Metz France
MONTPELLIER - Hôpital Saint-Eloi - Hématologie Clinique Montpellier France
MULHOUSE - Hôpital E. Muller - Hématologie Mulhouse France
NANTES - Hôpital Hôtel Dieu - Hématologie Clinique Nantes France
NIMES - CHU Caremeau Nîmes France
ORLEANS - CHR - Hématologie Orléans France
PERPIGNAN - CH St Jean - Hématologie Clinique Perpignan France
BORDEAUX - Hôpital Haut-Levêque Pessac France
POITIERS - Hôpital La Milétrie - Hématologie Clinique Poitiers France
REIMS - Hôpital Robert Debré - Hématologie Clinique Reims France
RENNES - Hôpital Pontchaillou - Hématologie Rennes France
ST ETIENNE - CHU et Institut De Cancérologie Lucien Neuwirth Saint-Priest-en-Jarez France
Strasbourg - Icans Strasbourg France
Toulouse - IUCT Oncopole - Service d'Hématologie Toulouse France
TOURS - Hôpital Bretonneau Tours France
NANCY - CHU de Brabois Vandœuvre-lès-Nancy France
Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT04968015 on ClinicalTrials.gov ↗ ← All trials in France