Clinical trial NCT03609060: Dexamethasone Added to Intensive Chemotherapy in Older Patients with Acute Myeloid Leukemia (AML)
Official title: A Phase II Study of Dexamethasone Added to Induction and Post-remission Therapy in Older Patients with Newly Diagnosed Acute Myeloid Leukemia (AML)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Keywords: Elderly patients
Lead sponsor: French Innovative Leukemia Organisation
Sponsor class: OTHER
First posted: 2018-08-01
Enrollment: 120
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: Patients will receive dexamethasone in addition to induction and post-remission chemotherapy

The principal objective of the study is to determine whether adding dexamethasone to induction and post-remission therapy results in significant improvement of event-free survival (EFS) as compared with an historical cohort of the FILO LAM-SA 2007 trial.

Induction therapy: Idarabucin + Cyrarabine + Lomustine (ICL) + Dexamethasone. 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.

Post remission therapy: Idarabucin + Cyrarabine (IC) + Dexamethasone

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.

Eligibility criteria: Inclusion Criteria:

1. \> 60 years of age.
2. 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)
3. AML with favorable or intermediate cytogenetic risk according to Medical Research Council (MRC 2010) classification.
4. Subjects should be eligible for intensive chemotherapy by Idarubicin, cytarabine, Lomustine.
5. Eastern Cooperative Oncology Group (ECOG) performance status \< 3 (appendix 1).
6. SORROR score ≤ 3 (appendix 2).
7. 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
8. Adequate cardiac function with Left Ventricular Ejection Fraction (LVEF) ≥50%
9. Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
10. Women will be menopausal to be enrolled
11. 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.
12. Affiliated to the French Social Security (Health Insurance).

Exclusion Criteria:

1. Acute promyelocytic leukemia (APL) or acute megakaryocytic leukemia (AML-FAB M7).
2. AML with adverse cytogenetic risk according to the MRC 2010 classification.
3. AML arising from myelodysplastic syndromes, myeloproliferative disorders or chronic myelo-monocytic leukemia according to WHO classification (2016).
4. AML with Philadelphia chromosome or with BCR-ABL1.
5. Known active central nervous system leukemia
6. Previous anti-AML treatment other than hydroxyurea.
7. Cumulative anthracycline dose equivalent to ≥550 mg/m².
8. Treatment with an investigational drug within 30 days or 5 half-life whichever is longer, preceding the first dose of study medication.
9. 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.
10. Severe medical or mental condition precluding the administration of protocol treatments
11. Any sign of active uncontrolled disease including but not restricted to cardiac disease, infections, hepatitis.
12. Any severe chronic disease potentially interfering with the protocol including HIV infection, active hepatitis B or C.
13. Any severe conditions inducing contra-indications to dexamethasone including uncontrolled diabetes, infections, hypertension, stomach ulcer, mental illness, myasthenia or glaucoma.
14. 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.
15. Known active HIV, Hepatitis B or C infection.
16. Pregnancy or breastfeeding.
17. Patients who are incapacitated, under wardship, legal guardianship, or under the protection of the courts.
18. Patients under State Medical Assistance (AME).

Primary outcomes:
measure: Event Free survival (EFS)
timeFrame: Within 2 years after the start of the Treatement
Secondary outcomes:
measure: Treatment response
timeFrame: Up to 45 day
measure: Minimal Residual Disease (MRD)
timeFrame: Up to day 45 after induction chemotherapy, second and last consolidation cycle.
measure: Allogenic Stem Cells Transplantation (ASCT)
timeFrame: Up to one year
measure: Remission duration (relapse from CR or CRi)
timeFrame: two years
measure: Relapse Free Survival (RFS)
timeFrame: two years
measure: Overall Survival (OS)
timeFrame: two years
measure: Adverse events
timeFrame: up to 60 months
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU ANGERS - Maladies du sang
city: Avignon
country: France
facility: Ch Avignon
city: Bayonne
country: France
facility: CH de la Côte Basque - Hématologie
city: Besançon
country: France
facility: CHRU JEAN MINJOZ - Hématologie
city: Brest
country: France
facility: CHU Brest - Hôpital Morvan - Hématologie Clinique
city: Béziers
country: France
facility: CH de Béziers - Hématologie
city: Castelnau-le-Lez
country: France
facility: Clinique du Parc - Hématologie
city: Clermont-Ferrand
country: France
facility: CHU Estaing - Hématologie Clinique Adulte
city: Grenoble
country: France
facility: CHU Grenoble - Hématologie Clinique
city: Marseille
country: France
facility: Institut Paoli-Calmettes - Hématologie 2
city: Metz
country: France
facility: CHR de Mercy - Hématologie
city: Montpellier
country: France
facility: Hôpital Saint-Eloi - Hématologie Clinique
city: Mulhouse
country: France
facility: HOPITAL E. MULLER - Hématologie
city: Nantes
country: France
facility: CHU HOTEL DIEU - Hématologie Clinique
city: Orléans
country: France
facility: CHR ORLEANS - Hématologie
city: Paris
country: France
facility: HOPITAL COCHIN - Hématologie
city: Perpignan
country: France
facility: CENTRE HOSPITALIER SAINTJEAN - Hématologie Clinique
city: Pessac
country: France
facility: Hôpital Haut Levêque- CFM -Hématologie Clinique Et Thérapie Cellulaire
city: Poitiers
country: France
facility: CHU La Milétrie - Hématologie Clinique
city: Reims
country: France
facility: CHU Reims - Hôpital Robert Debré - Hématologie Clinique
city: Rennes
country: France
facility: CHU Pontchaillou - Hématologie
city: Strasbourg
country: France
facility: CHU Hautepierre - Hématologie
city: Toulouse
country: France
facility: Institut Universitaire du Cancer de Toulouse Oncopole - Service d'Hématologie
city: Tours
country: France
facility: CHU Bretonneau - Centre Henri Kaplan - Hématologie et Thérapie Cellulaire
city: Vandœuvre-lès-Nancy
country: France
facility: CHU Nancy - Hopitaux Brabois
Study officials:
affiliation: +33 5 31 15 63 55
name: Christian RECHER, MD PD
role: PRINCIPAL_INVESTIGATOR
References: