Dexamethasone Added to Intensive Chemotherapy in Older Patients with Acute Myeloid Leukemia (AML) (DEXAML-02)

French Innovative Leukemia Organisation

Status and phase: Active, not recruiting; Phase 2

Conditions: Acute Myeloid Leukemia

Treatments: Drug: Dexamethasone

Study type: Interventional

Funder types: Other

Identifiers

NCT03609060

DEXAML-02 (LAM-SA 2018)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 120 estimated patients

Sex: All

Ages: 60+ years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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120 participants in 1 patient group

DEXAML

Experimental group

Description:

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

Treatment:

Drug: Dexamethasone