WT1 mRNA DC for Acute myeloid leukemia

Inclusion criteria

• {"criterion_text":"- Diagnosis of acute myeloid leukemia (AML) according to the 2008 criteria of the World Health Organization (WHO): A) All French-American-British (FAB) subtypes (except for M3 (acute promyelocytic leukemia)) B) All cases of de novo AML or secondary AML with ≥20 % blasts in peripheral blood and/or bone marrow (except for AML secondary to myeloproliferative neoplasms (MPN) and AML secondary to exposure of leukemogenic agents (therapy-related (t)-AML) unless treated with CPX-351 chemotherapy or hypomethylating agents combined with venetoclax)\n- Adult (≥18 years) at very high risk of relapse according to A) Age ≥60 years, and/or B) Adverse biological features (e.g. adverse cytogenetics, adverse morphological features, adverse molecular features, hyperleukocytosis (>100000 cells/µL)), and C) Ineligible for or unwilling to receive hematopoietic stem cell transplantation\n- 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 (HMA) whether or not combined with venetoclax (VEN) OR (4) At least two cycles to maximum six cycles of low-dose cytarabine (LDAC) combined with venetoclax]; resulting in: A) 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 B) 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)\n- 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)\n- 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

• {"criterion_text":"- Participation in any other interventional clinical trial during the study period\n- History or concomitant presence of any other malignancy, except for: A) Non-melanoma skin cancer B) Carcinoma in situ of the cervix C) 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\n- Known concomitant presence of any immunosuppressive disease (e.g. HIV) or any active autoimmune condition, except for vitiligo\n- 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\n- Pregnant or breast-feeding"}

Primary endpoints

• {"endpoint_text":"- Primary end point: Overall survival","definition_or_measurement_approach":""}

Secondary endpoints

• {"endpoint_text":"- Secondary end point 1 and 2: Clinical response analysis will be performed on all efficacy-evaluable patients according to the ‘Revised Recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia’. Secondary endpoints that will be analyzed are relapse-free survival and relapse rate at two years","definition_or_measurement_approach":"Clinical response analysis per the Revised Recommendations of the International Working Group for AML; relapse-free survival and relapse rate assessed at two years."}
• {"endpoint_text":"- Secondary end point 3: Both for the control group and the intervention group, tumor marker levels will be monitored in peripheral blood. This will be done by measuring WT1 mRNA levels using specific primers and quantitative real-time RT-PCR. Molecular response is defined as the normalization of WT1 transcript levels in peripheral blood below background","definition_or_measurement_approach":"Measurement of WT1 mRNA levels in peripheral blood by quantitative real-time RT-PCR using specific primers; molecular response defined as normalization of WT1 transcript levels in peripheral blood below background."}
• {"endpoint_text":"- Secondary end point 4: Both for the control group and the intervention group, activation of the immune system will be monitored. Peripheral blood samples will be examined by using flow cytometry for functional WT1-specific T cell responses (e.g. WT1-reactive IFN-γ+ T cells), WT1-specific CD8+ T cells (by tetramer analysis in HLA-A*0201+ patients) and changes in lymphocyte subset distribution and activation state","definition_or_measurement_approach":"Immune monitoring by flow cytometry for functional WT1-specific T cell responses (e.g. IFN-γ+), tetramer analysis for WT1-specific CD8+ T cells in HLA-A*0201+ patients, and analysis of lymphocyte subsets/activation."}
• {"endpoint_text":"- Secondary end point 5: Patient-reported outcomes, to evaluate changes in general and disease-specific quality of life using EQ-5D-5L and QLQ-C30 questionnaires at regular time points","definition_or_measurement_approach":"Patient-reported QoL measured using EQ-5D-5L and QLQ-C30 questionnaires at scheduled time points."}

Belgium

Earliest CTIS Part Ii Submission Date

29-10-2024

Latest Decision Or Authorization Date

22-01-2026

Processing Time Days

450

Number Of Sites

6

Number Of Participants

130

Primary sponsor

Full Name

Antwerp University Hospital

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Belgium