Wilms’ tumor (WT1) antigen-targeted dendritic cell vaccination to prevent relapse in adult patients with acute myeloid leukemia: a multicenter randomized phase II trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Antwerp University Hospital

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02], Diseases [C] - Hemic and Lymphatic Diseases [C15], Phenomena and Processes [G] - Immune system processes [G12]

Trial duration

9 Jan 2026 → ongoing

Decision date (initial)

2024-10-31

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-515292-35-00

EudraCT number

2012-001494-91

ClinicalTrials.gov

NCT01686334

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

Clinical response: To determine the clinical efficacy of WT1 mRNA-electroporated DC vaccination as a post-remission strategy to prevent relapse and prolong overall survival in adult AML patients

Secondary objectives 4

1. Clinical response: To assess the relapse rate (2 years after the date that morphological CR or CRi was demonstrated on bone marrow examination) and the relapse free survival of WT1 mRNA-electroporated DC vaccination in adult patients with AML
2. Molecular response: To determine the efficacy of the DC vaccine strategy to control or eradicate minimal residual disease (MRD) in AML. Monitoring of MRD will be performed by sequential measurement of WT1 transcript levels in peripheral blood
3. Immunological response: To investigate if the WT1 mRNA-electroporated DC vaccines are immunogenic and capable of inducing anti-leukemic immune responses in vivo by using different immunoassays
4. 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

Conditions and MedDRA coding

Acute Myeloid Leukemia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. 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)
2. 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
3. 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)
4. 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)
5. 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 5

1. Participation in any other interventional clinical trial during the study period
2. 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
3. Known concomitant presence of any immunosuppressive disease (e.g. HIV) or any active autoimmune condition, except for vitiligo
4. 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
5. Pregnant or breast-feeding

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary end point: Overall survival

Secondary endpoints 4

1. 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
2. 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
3. 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
4. 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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Antwerp University Hospital

Sponsor organisation

Antwerp University Hospital

Address

Drie Eikenstraat 655

City

Edegem

Postcode

2650

Country

Belgium

Scientific contact point

Organisation

Antwerp University Hospital

Contact name

Center for Cell Therapy and Regenerative Medicine

Public contact point

Organisation

Antwerp University Hospital

Contact name

Center for Cell Therapy and Regenerative Medicine

Locations

1 EU/EEA country · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications