Dexamethasone in Refractory or First Relapsed Acute Myeloid Leukemia

NCT03765541 | Terminated Phase 3 DMC

• 1 other identifier: RC31/17/0450
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 10

Brief Summary

Recent preclinical and retrospective clinical data have suggested that dexamethasone might sensitize leukemic cells to chemotherapy-induced cell death and thus limit the risk of leukemic regrowth and relapse. Moreover, it has been experimentally shown that leukemic cells in acute myeloid leukemia patients who relapse become sensitive to glucocorticoids treatment highlighting a novel potential role for dexamethasone in relapsed or refractory acute myeloid leukemia (R/R). This study was designed to determine whether adding dexamethasone to standard salvage therapy in the treatment of relapsed/refractory acute myeloid leukemia in adult patients (intensive chemotherapy amsacrine-cytarabine or azacitidine according to investigator's willingness) results in a significant improvement of the overall survival.

Conditions

Relapsed or Refractory Acute Myeloid Leukemia

Keywords

dexamethasone; acute myeloid leukemia; relapse; refractory; azacitidine; amsacrine; cytarabine; randomized controlled trial

Outcome Measures

Primary Outcomes (1)

• Overall survival

  Time from the date of randomization to the date of death from any cause

  Up to 60 months

Secondary Outcomes (8)

• Response to therapy

  Up to 60 months

• Minimal residual disease positivity

  Up to 60 months

• Number of patient who realize allogeneic hematopoietic stem cell transplantation

  Up to 60 months

• Duration of remission

  Up to 60 months

• Relapse-free survival

  Up to 60 months

Study Arms (2)

Standard salvage therapy + dexamethasone

EXPERIMENTAL

Intensive chemotherapy amsacrine-cytarabine or azacitidine according to the investigator's willingness in combination with dexamethasone

Drug: Dexamethasone; Drug: Amsacrine; Drug: Cytarabine; Drug: Azacitidine

Standard salvage therapy alone

ACTIVE COMPARATOR

Intensive chemotherapy amsacrine-cytarabine or azacitidine according to the investigator's willingness

Drug: Amsacrine; Drug: Cytarabine; Drug: Azacitidine

Interventions

Dexamethasone DRUG

In combination with intensive chemotherapy amsacrine-cytarabine: * Induction (1 cycle): 10 mg/12h from Day 1 to Day 3 of cycle (2 infusions/24h, slow IV \[10 minutes\]) * Consolidation (3 cycles): 10 mg/12h from Day 1 to Day 3 of each cycle (2 infusions/24h, slow IV \[10 minutes\]) In combination with azacitidine: * Cycle 1: 20 mg/24h from Day 1 to Day 3 of cycle (1 infusion/24h, slow IV \[10 minutes\]). * Subsequent cycles: 20 mg/24h on Day 1 of each cycle (1 infusion/24h, slow IV \[10minutes\]).

Standard salvage therapy + dexamethasone

Amsacrine DRUG

* Induction (1 cycle): 200 mg/m2/24h from Day 1 to Day 3 of cycle (slow IV \[3 hours\]) * Consolidation (3 cycles): 200 mg/m2/24h on Day 1 of each cycle (slow IV \[3 hours\])

Standard salvage therapy + dexamethasone; Standard salvage therapy alone

Cytarabine DRUG

Patients \< 60 years of age: * Induction (1 cycle): 3 g/m2/12h from Day 1 to Day 4 of cycle (2 infusions/24h, slow IV \[2 hours\]) * Consolidation (3 cycles): 3 g/m2/12h from Day 1 to Day 3 of each cycle (2 infusions/24h, slow IV \[2 hours\]) Note: If the investigators believe that there is an undue risk for the safety of a patient under 60 years of age with comorbidity in receiving a dose level of 3 g/m2/12h, the dose may be reduced to 1 g/m2/12h

Standard salvage therapy + dexamethasone; Standard salvage therapy alone

Azacitidine DRUG

75 mg/m2/24h from Day 1 to Day 7 of each cycle \[or from Day 1 to Day 5 and from Day 8 to Day 9 of each cycle\] (SC)

Standard salvage therapy + dexamethasone; Standard salvage therapy alone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least 18 years of age or older
• Diagnosis of acute myeloid leukemia by World Health Organization classification
• First relapsed or refractory acute myeloid leukemia with at least 5% blasts by bone marrow biopsy or aspirate, or at least 1% blasts in peripheral blood, and meeting the following criteria:
• First relapsed acute myeloid leukemia :
• First relapse occurred at least 90 days to 24 months after the first complete remission or complete remission with incomplete recovery
• The first complete remission or complete remission with incomplete recovery had to result from no more than 2 cycles of cytotoxic chemotherapy. At least 1 induction cycle must have consisted of an anthracycline and cytarabine combination with a reasonable schedule/dose of anthracycline in the judgment of the investigator.
• The re-emergence of at least 5% leukemic blasts in bone marrow is not attributable to other causes, regardless of new or recurrent dysplastic changes or extramedullary disease, or the re-emergence of at least 1% blasts in the peripheral blood is not attributable to other causes such as regenerating marrow.
• Refractory acute myeloid leukemia :
• Persistent acute myeloid leukemia was documented by bone marrow biopsy or aspirate at least 28 days after day 1 of the first induction cycle of 1 or 2 cycles of cytotoxic chemotherapy.
• Re-emergence of at least 5% leukemic blasts in bone marrow or at least 1% blasts in peripheral blood is not attributable to other causes such as regenerating marrow, and was less than 90 days after the first complete remission or complete remission with incomplete recovery.
• Prior induction therapy had to include no more than 2 cycles of cytotoxic chemotherapy. At least 1 induction cycle must have consisted of an anthracycline and cytarabine combination with a reasonable schedule/dose of anthracycline in the judgment of the investigator.
• Eastern Cooperative Oncology Group performance status ≤ 2.
• Left ventricular ejection fraction ≥ 50% by echocardiogram or multi-gated acquisition scan ; only applicable for patients who will receive intensive chemotherapy.
• Serum creatinine ≤ 150 µmol/L and/or total bilirubin ≤ 1.5 × the upper limit of normal and/or, aspartate aminotransferase ≤ 2.5 × the upper limit of normal, and/or alanine aminotransferase ≤ 2.5 × the upper limit of normal (unless related to acute myeloid leukemia)
• Any clinically significant non-hematological toxicity after prior chemotherapy must be resolved or of grade 1 as per Common Terminology Criteria for Adverse Events version 4.03.

You may not qualify if:

• Acute promyelocytic leukemia (M3 subtype of acute myeloid leukemia).
• More than 2 cycles of first line induction chemotherapy.
• Acute myeloid leukemia with Philadelphia chromosome or BCR-ABL1 or blast crisis stage of chronic myeloid leukemia.
• Known or suspected central nervous system leukemia.
• Undergoing allogeneic hematopoietic stem cell transplantation within 90 days prior to randomization, or being on immunosuppressive therapy for prophylaxis of graft-versus-host disease, or experiencing graft-versus-host disease within 2 weeks prior to randomization.
• Use of any experimental, cytotoxic, or targeted, anti-leukemic therapy within 14 days prior to randomization, with the exception of hydroxyurea.
• Formal contraindication to glucocorticoids.
• Non-acute myeloid leukemia-associated organic or psychiatric severe disease that contraindicates use of study treatment.
• Patient who may not be followed regularly in consultation because of psychological, family, social, or geographical reasons.
• History of uncontrolled other malignancy for at least two years, with the exception of basal cell carcinoma and in situ cervix carcinoma.
• Positive serology for human immunodeficiency virus-1 or 2, and/or Human T-Cell lymphotropic viruses-1 or 2, and/or active viral infection with hepatitis B virus and/or hepatitis C virus.
• Pregnant (beta gonadotropic chorionic hormon positive) or breastfeeding woman.
• Incapable patient of age, under guardianship, under curators or safeguard of justice.
• Patient under State Medical Assistance.

Sponsors & Collaborators

• University Hospital, Toulouse: lead

Study Sites (10)

CH de la Côte Basque

Bayonne, France, 64100, France

Location

CHU de la Réunion

Saint-Pierre, France, 97448, France

Location

CHU de Grenoble

Grenoble, France

Location

CHU de Limoges

Limoges, France

Location

Institut Paoli Calmettes

Marseille, France

Location

CHU de Montpellier

Montpellier, France

Location

CHU de Nantes

Nantes, France

Location

CHU de Nîmes

Nîmes, France

Location

CHU de Bordeaux

Pessac, France

Location

CHU de Poitiers

Poitiers, France

Location

MeSH Terms

Conditions

Recurrence; Leukemia, Myeloid, Acute

Interventions

Dexamethasone; Amsacrine; Cytarabine; Azacitidine

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; 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; Aminoacridines; Acridines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Aza Compounds; Organic Chemicals; Ribonucleosides

Study Officials

• Christian RECHER, PhD

  University Hospital, Toulouse

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2018
• First Posted: December 5, 2018
• Study Start: January 13, 2020
• Primary Completion: May 31, 2024
• Study Completion: May 31, 2024
• Last Updated: April 10, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (10)