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

NCT04968015 | Active Not Recruiting Phase 2

• 1 other identifier: LAMSA2020
• Study Type: interventional
• Target: 134
• Locations: 1 country
• Sites: 26

Brief 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.

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Relapse Free Survival (RFS)

  RFS measured from the date of achievement of a remission until the date of relapse or death from any cause

  from randomization to last follow-up (up to 5 years)

Secondary Outcomes (1)

• Overall survival at 2 years

  from date of randomization to 2 years after last administration of experimental treatment

Study Arms (2)

VEN-CYTA

EXPERIMENTAL

Venetoclax 600mg/day, Per Os (PO), D1 to D14 / 28 days cycle Cytarabine 50 mg/m2/12h Subcutaneous (SC), D1 to D5 / 28 days cycle

Drug: Cytarabine-Venetoclax Association

IDA-CYTA

ACTIVE COMPARATOR

Idarubicin 8mg/m2, Intravenous (IV), at D1 / 28 days cycle Cytarabine 50 mg/m2/12h, SC, D1 to D5 / 28 days cycle

Drug: Cytarabine-Idarubicin Association

Interventions

Cytarabine-Venetoclax Association DRUG

Consolidation treatment with cytarabine + venetoclax

VEN-CYTA

Cytarabine-Idarubicin Association DRUG

Consolidation treatment with cytarabine + idarubicin

IDA-CYTA

Eligibility Criteria

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

You may qualify if:

• ≥ 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

You may not qualify if:

• 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
• Randomization criteria:
• Subjects must have been registered at diagnosis
• Subjects must have received intensive induction by Idarubicin, Cytarabine and Lomustine
• Patients in Complete Response / Complete Response with incomplete hematologic recovery (CR/CRi) post induction according to ELN 2017 criteria

Sponsors & Collaborators

• French Innovative Leukemia Organisation: lead

Study Sites (26)

ANGERS - CHU - Maladies du sang

Angers, 49933, France

Location

ANNECY - Centre Hospitalier Annecy-Genevois

Annecy, 74374, France

Location

AVIGNON - Centre Hospitalier

Avignon, 84000, France

Location

BAYONNE - CH de la Côte Basque - Hématologie

Bayonne, 64109, France

Location

BESANCON - Hôpital Jean Minjoz - Hématologie

Besançon, 25030, France

Location

BEZIERS - Centre Hospitalier - Hématologie

Béziers, 34500, France

Location

Clermont-Ferrand - Chu Estaing

Clermont-Ferrand, 63000, France

Location

Grenoble - CHUGA - Hématologie Clinique

Grenoble, 38043, France

Location

LYON-Centre Léon Bérard

Lyon, 69008, France

Location

MARSEILLE - Institut Paoli-Calmettes

Marseille, 13000, France

Location

METZ - CHR Metz-Thionville

Metz, 57085, France

Location

MONTPELLIER - Hôpital Saint-Eloi - Hématologie Clinique

Montpellier, 34295, France

Location

MULHOUSE - Hôpital E. Muller - Hématologie

Mulhouse, 68070, France

Location

NANTES - Hôpital Hôtel Dieu - Hématologie Clinique

Nantes, 44093, France

Location

NIMES - CHU Caremeau

Nîmes, 30029, France

Location

ORLEANS - CHR - Hématologie

Orléans, 44100, France

Location

PERPIGNAN - CH St Jean - Hématologie Clinique

Perpignan, 66000, France

Location

BORDEAUX - Hôpital Haut-Levêque

Pessac, 33600, France

Location

POITIERS - Hôpital La Milétrie - Hématologie Clinique

Poitiers, 86000, France

Location

REIMS - Hôpital Robert Debré - Hématologie Clinique

Reims, 51100, France

Location

RENNES - Hôpital Pontchaillou - Hématologie

Rennes, 35033, France

Location

ST ETIENNE - CHU et Institut De Cancérologie Lucien Neuwirth

Saint-Priest-en-Jarez, France

Location

Strasbourg - Icans

Strasbourg, 67033, France

Location

Toulouse - IUCT Oncopole - Service d'Hématologie

Toulouse, 31059, France

Location

TOURS - Hôpital Bretonneau

Tours, 37000, France

Location

NANCY - CHU de Brabois

Vandœuvre-lès-Nancy, 54500, France

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

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

Study Officials

• Arnaud PIGNEUX, Pr

  FILO (French Innovative Leukemia Organization)

  PRINCIPAL INVESTIGATOR

• Yosr HICHERI

  FILO (French Innovative Leukemia Organization)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase II open label controlled study. Subjects will be randomized 1:1 to receive Venetoclax or Idarubicin associated to Cytarabine

Study Record Dates

• First Submitted: July 13, 2021
• First Posted: July 20, 2021
• Study Start: May 25, 2022
• Primary Completion: August 15, 2025
• Study Completion (Estimated): January 31, 2029
• Last Updated: June 27, 2024

Record last verified: 2024-06

Locations

FR (26)