Efficacy Study of Dendritic Cell Vaccination in Patients With Acute Myeloid Leukemia in Remission (WIDEA)

This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring in complete remission, Adult (>18 years) at very high risk of relapse Read More

Inclusion Criteria:

• Diagnosis of acute myeloid leukemia (AML) according to the 2008 criteria of the World Health Organization (WHO).

  • all French-American-British (FAB) subtypes, except:

    - M3 (acute promyelocytic leukemia)

  • all cases of de novo AML or secondary AML with ≥ 20 % blasts in peripheral blood and/or bone marrow, except:

    • AML secondary to myeloproliferative neoplasms (MPN)
    • AML secondary to exposure of leukemogenic agents (t-AML) unless treated with CPX-351 chemotherapy or hypomethylating agents combined with venetoclax.

• Completion of one of the following treatment options:

  • I) Intensive chemotherapy:

    • (1) at least one cycle of induction chemotherapy and one cycle of consolidation chemotherapy (low-dose cytarabine as consolidation therapy is allowed) OR
    • (2) one to two cycles of CPX-351 induction treatment and up to two cycles of CPX-351 consolidation treatment OR

  • II) Low-intensity chemotherapy:

    • (3) at least two cycles to maximum six cycles of hypomethylating agents whether or not combined with venetoclax OR
    • (4) at least two cycles to maximum six cycles of low-dose cytarabine combined with venetoclax;

  • resulting in:

    • morphological complete remission (CR), i.e. bone marrow blast count <5% with neutrophil count >1000 cells/µL and platelet count >100,000 cells/µL OR
    • morphological complete remission with incomplete blood recovery (CRi), i.e. bone marrow blast count <5% with neutrophil count <1000 cells/µL or platelet count <100,000 cells/µL.

For the purpose of this study protocol, platelet count must be >50,000 cells/µL.

• Interval between the completion of the last intensive chemotherapy administration (in case of low-intensity chemotherapy: last cycle (min. 2 to max. 6 cycles) before achieving CR or CRi) and the start of vaccination (or the start of follow-up in case of the control arm): 6 weeks (minimum) and 16 weeks (maximum) (in case of low-intensity chemotherapy: maximum 10 weeks).

• Adult (≥ 18 years) at very high risk of relapse according to:

  • Age ≥ 60 years, and/or
  • Adverse biological features (e.g. adverse cytogenetics, adverse morphological features, adverse molecular features, hyperleukocytosis (> 100000 cells/µL)), and
  • Ineligible for or unwilling to receive hematopoietic stem cell transplantation.
• WHO performance status: grade 0, 1 or 2 at the time of enrollment. For definition of performance status, see: http://www.ecog.org/general/perf_stat.html
• Absence of any psychological, familial, sociological, geographical or physical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before study entry.

Exclusion Criteria:

• Participation in any other interventional clinical trial during the study period.

• History or concomitant presence of any other malignancy, except for:

  • non-melanoma skin cancer
  • carcinoma in situ of the cervix
  • any other effectively treated malignancy that has been in remission for >5 years or that is highly likely to be cured at the time of enrollment.
• Concomitant presence of any immunosuppressive disease (e.g. HIV) or any active autoimmune condition, except for vitiligo.
• Concomitant use of systemic corticosteroids in immunosuppressive doses (>1 mg/kg/day of prednisone, or equivalent dose for other corticosteroid preparations) or any other immunosuppressive agent. A minimum of 4 weeks must have elapsed between the last dose of immunosuppressive therapy and the first vaccination. Topical corticosteroids are permitted, except if applied at the sites of DC injection.
• Pregnant or breast-feeding