Dexamethasone Added to Intensive Chemotherapy in Older Patients with Acute Myeloid Leukemia (AML)

NCT03609060 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: DEXAML-02 (LAM-SA 2018)
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 25

Brief Summary

Recent preclinical and clinical data strongly suggested that dexamethasone could improve the activity of intensive chemotherapy in AML. In this study, the FILO study group will assess the impact of adding dexamethasone to both induction and consolidation therapy in older AML patients with intermediate or favorable risk.

Conditions

Acute Myeloid Leukemia

Keywords

Elderly patients

Outcome Measures

Primary Outcomes (1)

• Event Free survival (EFS)

  Time from the date of induction start to the date of induction failure, relapse from CR or CRi, or death from any cause, whichever occurs first. CR, CRi, relapse from CR or CRi and induction failure are defined according to the ELN 2017 recommendations

  Within 2 years after the start of the Treatement

Secondary Outcomes (7)

• Treatment response

  Up to 45 day

• Minimal Residual Disease (MRD)

  Up to day 45 after induction chemotherapy, second and last consolidation cycle.

• Allogenic Stem Cells Transplantation (ASCT)

  Up to one year

• Remission duration (relapse from CR or CRi)

  two years

• Relapse Free Survival (RFS)

  two years

Study Arms (1)

DEXAML

EXPERIMENTAL

Induction therapy: Idarubicin 8 mg/m²/day, IV over 15 minutes, D1 to D5 + Cytarabine 100 mg/m²/d, IV continuous 24h-infusion D1 to D7 + Lomustine 200 mg/m²/d, orally at D1 + Dexamethasone 10 mg/12h, IV over 30 minutes, D1 to D3. Addition of midostaurin in patients with Fms-like tyrosine kinase 3-internal tandem ( FLT3-ITD) or Fms-like tyrosine kinase 3-tyrosine kinase domain (FLT3-TKD) mutations is allowed. Post remission therapy: Idarubicin 8 mg/m², IV over 15 minutes, D1 + Cytarabine 50 mg/m²/12h, subcutaneous, D1 to D5 + Dexamethasone 20 mg/d, IV over 30 minutes, D1. Addition of midostaurin in patients with FLT3-ITD or FLT3-TKD mutations is allowed. Intermediate dose cytarabine is allowed for patients with Core Binding Factor AML (CBF-AML). Allogeneic stem-cell transplantation allowed after 2 to 4 cycles

Drug: Dexamethasone

Interventions

Dexamethasone DRUG

Dexamethasone 10 mg/12h, IV over 30 minutes, D1 to D3 concomitant to induction and post remission chemotherapy in elderly patients with AML Induction

DEXAML

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.
• Newly diagnosed AML according to the World Health Organization (WHO) 2016 either de novo AML or therapy-related AML (i.e AML arising after previous cytotoxic therapy or radiation)
• AML with favorable or intermediate cytogenetic risk according to Medical Research Council (MRC 2010) classification.
• Subjects should be eligible for intensive chemotherapy by Idarubicin, cytarabine, Lomustine.
• Eastern Cooperative Oncology Group (ECOG) performance status \< 3 (appendix 1).
• SORROR score ≤ 3 (appendix 2).
• Adequate baseline organ function defined by the criteria below:
• Total bilirubin ≤ 1.5 x Upper Limit of Normal (ULN) unless bilirubin rise is due to Gilbert's syndrome
• Alanine Aminotransferase (ALAT) and Aspartate Transaminase (ASAT) ≤ 3xULN
• creatinin clearance (Cockcroft-Gault) ≥ 30 ml/min
• Unless considered due to leukemic organ involvement
• 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.

You may not qualify if:

• Acute promyelocytic leukemia (APL) or acute megakaryocytic leukemia (AML-FAB M7).
• AML with adverse cytogenetic risk according to the MRC 2010 classification.
• AML arising from myelodysplastic syndromes, myeloproliferative disorders or chronic myelo-monocytic leukemia according to WHO classification (2016).
• AML with Philadelphia chromosome or with BCR-ABL1.
• Known active central nervous system leukemia
• Previous anti-AML treatment other than hydroxyurea.
• Cumulative anthracycline dose equivalent to ≥550 mg/m².
• Treatment with an investigational drug within 30 days or 5 half-life whichever is longer, preceding the first dose of study medication.
• Prior history of cancer unless controlled for at least 2 years and except for basal cell carcinoma, non-melanoma skin cancer and in situ cervical carcinoma.
• Severe medical or mental condition precluding the administration of protocol treatments
• Any sign of active uncontrolled disease including but not restricted to cardiac disease, infections, hepatitis.
• Any severe chronic disease potentially interfering with the protocol including HIV infection, active hepatitis B or C.
• Any severe conditions inducing contra-indications to dexamethasone including uncontrolled diabetes, infections, hypertension, stomach ulcer, mental illness, myasthenia or glaucoma.
• 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

Study Sites (25)

CHU ANGERS - Maladies du sang

Angers, 49933, France

Location

Ch Avignon

Avignon, 84000, France

Location

CH de la Côte Basque - Hématologie

Bayonne, 64109, France

Location

CHRU JEAN MINJOZ - Hématologie

Besançon, 25030, France

Location

CH de Béziers - Hématologie

Béziers, 34500, France

Location

CHU Brest - Hôpital Morvan - Hématologie Clinique

Brest, 29609, France

Location

Clinique du Parc - Hématologie

Castelnau-le-Lez, 34170, France

Location

CHU Estaing - Hématologie Clinique Adulte

Clermont-Ferrand, 63000, France

Location

CHU Grenoble - Hématologie Clinique

Grenoble, 38043, France

Location

Institut Paoli-Calmettes - Hématologie 2

Marseille, 13000, France

Location

CHR de Mercy - Hématologie

Metz, 57085, 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

CHR ORLEANS - Hématologie

Orléans, 44100, France

Location

HOPITAL COCHIN - Hématologie

Paris, 75014, France

Location

CENTRE HOSPITALIER SAINTJEAN - Hématologie Clinique

Perpignan, 66000, France

Location

Hôpital Haut Levêque- CFM -Hématologie Clinique Et Thérapie Cellulaire

Pessac, 33604, France

Location

CHU La Milétrie - Hématologie Clinique

Poitiers, 86000, France

Location

CHU Reims - Hôpital Robert Debré - Hématologie Clinique

Reims, 51100, France

Location

CHU Pontchaillou - Hématologie

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

CHU Bretonneau - Centre Henri Kaplan - Hématologie et Thérapie Cellulaire

Tours, 37044, France

Location

CHU Nancy - Hopitaux Brabois

Vandœuvre-lès-Nancy, 54500, France

Location

Related Links

• FILO Internet site

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Dexamethasone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Christian RECHER, MD PD

  +33 5 31 15 63 55

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: June 28, 2018
• First Posted: August 1, 2018
• Study Start: August 24, 2018
• Primary Completion: August 31, 2025
• Study Completion: December 31, 2025
• Last Updated: October 29, 2024

Record last verified: 2024-10

Locations

FR (25)