Dexamethasone in Refractory or First Relapsed Acute Myeloid Leukemia

• Status: Recruiting
• Trial end date: 2024-09-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital, Toulouse
• Treatments: Amsacrine; Azacitidine; BB 1101; Cytarabine; Dexamethasone; Dexamethasone acetate

Criteria

Inclusion Criteria:

1. At least 18 years of age or older

2. 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.

3. Eastern Cooperative Oncology Group performance status ≤ 2.

4. Left ventricular ejection fraction ≥ 50% by echocardiogram or multi-gated acquisition scan ; only applicable for patients who will receive intensive chemotherapy.

5. 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)

6. 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.

7. Women must be surgically or biologically sterile, or in post-menopause (amenorrheic for at least 12 months), or if of childbearing potential, must have a negative urine or serum pregnancy test within 14 days prior to the randomization and agree to use a highly effective method of contraception throughout the entire duration of the study treatment (including dose interruptions) and until 3 months after the last study treatment administration. Men must be surgically or biologically sterile, or agree to use a highly effective method of contraception throughout the entire duration of the study treatment (including dose interruptions) and until 6 months after the last study treatment administration.

8. Registered to, or beneficiary of, social security insurance or equivalent.

9. Signed written informed consent by both the patient and the investigator prior to perform any study-relayed procedure not part of normal medical care.

Exclusion Criteria:

1. Acute promyelocytic leukemia (M3 subtype of acute myeloid leukemia).

2. More than 2 cycles of first line induction chemotherapy.

3. Acute myeloid leukemia with Philadelphia chromosome or BCR-ABL1 or blast crisis stage of chronic myeloid leukemia.

4. Known or suspected central nervous system leukemia.

5. 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.

6. Use of any experimental, cytotoxic, or targeted, anti-leukemic therapy within 14 days prior to randomization, with the exception of hydroxyurea.

7. Formal contraindication to glucocorticoids.

8. Non-acute myeloid leukemia-associated organic or psychiatric severe disease that contraindicates use of study treatment.

9. Patient who may not be followed regularly in consultation because of psychological, family, social, or geographical reasons.

10. History of uncontrolled other malignancy for at least two years, with the exception of basal cell carcinoma and in situ cervix carcinoma.

11. Severe uncontrolled infection at time of inclusion.

12. 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.

13. Pregnant (beta gonadotropic chorionic hormon positive) or breastfeeding woman.

14. Incapable patient of age, under guardianship, under curators or safeguard of justice.

15. Patient under State Medical Assistance.