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

Acute Myeloid Leukemia Clinical Trial

— DEXAML-02  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03609060
• Other study ID #: DEXAML-02 (LAM-SA 2018)
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 24, 2018
• Est. completion date: December 31, 2025

Study information

• Verified date: July 2022
• Source: French Innovative Leukemia Organisation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 120
• Est. completion date: December 31, 2025
• Est. primary completion date: August 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

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

Locations

Country	Name	City	State
France	CHU ANGERS - Maladies du sang	Angers
France	Ch Avignon	Avignon
France	CH de la Côte Basque - Hématologie	Bayonne
France	CHRU JEAN MINJOZ - Hématologie	Besançon
France	CH de Béziers - Hématologie	Béziers
France	CHU Brest - Hôpital Morvan - Hématologie Clinique	Brest
France	Clinique du Parc - Hématologie	Castelnau-le-Lez
France	CHU Estaing - Hématologie Clinique Adulte	Clermont-Ferrand
France	CHU Grenoble - Hématologie Clinique	Grenoble
France	Institut Paoli-Calmettes - Hématologie 2	Marseille
France	CHR de Mercy - Hématologie	Metz
France	Hôpital Saint-Eloi - Hématologie Clinique	Montpellier
France	HOPITAL E. MULLER - Hématologie	Mulhouse
France	CHU HOTEL DIEU - Hématologie Clinique	Nantes
France	CHR ORLEANS - Hématologie	Orléans
France	HOPITAL COCHIN - Hématologie	Paris
France	CENTRE HOSPITALIER SAINTJEAN - Hématologie Clinique	Perpignan
France	Hôpital Haut Levêque- CFM -Hématologie Clinique Et Thérapie Cellulaire	Pessac
France	CHU La Milétrie - Hématologie Clinique	Poitiers
France	CHU Reims - Hôpital Robert Debré - Hématologie Clinique	Reims
France	CHU Pontchaillou - Hématologie	Rennes
France	CHU Hautepierre - Hématologie	Strasbourg
France	Institut Universitaire du Cancer de Toulouse Oncopole - Service d'Hématologie	Toulouse
France	CHU Bretonneau - Centre Henri Kaplan - Hématologie et Thérapie Cellulaire	Tours
France	CHU Nancy - Hopitaux Brabois	Vandœuvre-lès-Nancy

Sponsors (1)

Lead Sponsor	Collaborator
French Innovative Leukemia Organisation

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Treatment response	Response to therapy after induction therapy defined as CR or CRi according to the 2017 European Leukemia Net (ELN) recommendations.	Up to 45 day
Secondary	Minimal Residual Disease (MRD)	Presence of MRD after induction therapy and after post-remission therapy, measured by either quantitative PCR or flow cytometry	Up to day 45 after induction chemotherapy, second and last consolidation cycle.
Secondary	Allogenic Stem Cells Transplantation (ASCT)	Number of patients with ASCT	Up to one year
Secondary	Remission duration (relapse from CR or CRi)	Time from the date of CR or CRi to the date of relapse according to the 2017 ELN recommendations	two years
Secondary	Relapse Free Survival (RFS)	Time from the date of CR or CRi to the date of relapse or death from any cause, whichever occurs first, according to the ELN 2017 recommendations	two years
Secondary	Overall Survival (OS)	Time from the date of randomization to the date of death from any cause	two years
Secondary	Adverse events	Incidence and severity of Adverse Events according to the descriptions and grading scale found in the National Cancer Institute - Common Terminology Criteria (NCI-CTC) criteria v4.03	up to 60 months

External Links

•   FILO Internet site