Clinical Trials /

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

NCT03609060

Description:

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.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: DEXAML-02 (LAM-SA 2018)
  • NCT ID: NCT03609060

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
DexamethasoneDEXAML

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
DEXAMLExperimentalInduction 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
  • Dexamethasone

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).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:60 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Event Free survival (EFS)
Time Frame:Within 2 years after the start of the Treatement
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:Treatment response
Time Frame:Up to 45 day
Safety Issue:
Description:Response to therapy after induction therapy defined as CR or CRi according to the 2017 European Leukemia Net (ELN) recommendations.
Measure:Minimal Residual Disease (MRD)
Time Frame:Up to day 45 after induction chemotherapy, second and last consolidation cycle.
Safety Issue:
Description:Presence of MRD after induction therapy and after post-remission therapy, measured by either quantitative PCR or flow cytometry
Measure:Allogenic Stem Cells Transplantation (ASCT)
Time Frame:Up to one year
Safety Issue:
Description:Number of patients with ASCT
Measure:Remission duration (relapse from CR or CRi)
Time Frame:two years
Safety Issue:
Description:Time from the date of CR or CRi to the date of relapse according to the 2017 ELN recommendations
Measure:Relapse Free Survival (RFS)
Time Frame:two years
Safety Issue:
Description: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
Measure:Overall Survival (OS)
Time Frame:two years
Safety Issue:
Description:Time from the date of randomization to the date of death from any cause
Measure:Adverse events
Time Frame:up to 60 months
Safety Issue:
Description: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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:French Innovative Leukemia Organisation

Trial Keywords

  • Elderly patients

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