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Acute Myeloid LeukemiaPhase 2WIDEANCT01686334

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

A Phase 2 study testing DC vaccine in people with Acute Myeloid Leukemia, run by Zwi Berneman at 8 sites in Belgium.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

The primary aim of this innovative immunotherapeutic study is to determine whether the antileukemic effects seen in our previous phase I/II study can be confirmed in a large cohort of patients and whether dendritic cell vaccination can significantly prevent relapse and increase survival of acute myeloid leukemia (AML)… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
DC vaccine
Type of treatment
Vaccines
Could I receive a placebo?
No, everyone receives an active treatment
How many people
130 participants
Where
8 sitesBelgium
Study dates
Oct 2012to Dec 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 23Show fewer
  • 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.
  • 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.

Who cannot join

  • 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

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

Belgium8 sites

  • ZNA Cadix

    Antwerp, 2030

  • Antwerp University Hospital

    Antwerp, 2650

  • University Hospital Brussels

    Brussels, 1090

  • Cliniques Universitaires Saint-Luc

    Brussels, 1200

  • Ghent University Hospital

    Ghent, 9000

  • Centre Hospitalier Universitaire de Liège

    Liège, 4000

  • AZ Delta

    Roeselare, 8800

  • CHU Mont Godinne

    Yvoir, 5530

Other trials in Belgium

About this study

Official title: Wilms' Tumor (WT1) Antigen-targeted Dendritic Cell Vaccination to Prevent Relapse in Adult Patients With Acute Myeloid Leukemia: a Multicenter Randomized Phase II Trial

The primary aim of this innovative immunotherapeutic study is to determine whether the antileukemic effects seen in our previous phase I/II study can be confirmed in a large cohort of patients and whether dendritic cell vaccination can significantly prevent relapse and increase survival of acute myeloid leukemia (AML) patients by eradicating minimal residual disease.

Read the detailed description

Together with the Transplant Committee of the Belgian Hematological Society (BHS), we will perform a multicenter randomized open-label phase II clinical study in 130 patients with acute myeloid leukemia (AML). Adult patients (> 18 years) with AML who have entered morphological CR or CRi after (1) intensive chemotherapy (i.e (i) at least one cycle of induction and one cycle of consolidation chemotherapy or (ii) one to two cycles of CPX-351 induction treatment and up to two cycles of CPX-351 consolidation treatment) or (2) low-intensity chemotherapy (i.e (iii) at least two cycles to maximum six cycles of hypomethylating agents whether or not combined with venetoclax or (iv) at least two cycles to maximum six cycles of low-dose cytarabine combined with venetoclax); and fulfilling all other eligibility criteria will be randomized to be vaccinated with dendritic cells or to receive regular follow-up care. After randomization, patients receiving low-intensity chemotherapy are allowed to continue this treatment in combination with DC vaccination or the follow-up care. The primary aim of this innovative immunotherapeutic study is to determine whether the antileukemic effects seen in our previous phase I/II study can be confirmed in a large cohort of patients and whether dendritic cell vaccination can significantly prevent relapse and increase survival of AML patients by eradicating minimal residual disease. Patients will be recruited at 8 different centers in Belgium. Recruitment will start in the second half of 2013 and will last for 10 years or until 130 efficacy-evaluable AML patients are included. In the interventional group, 65 patients will be treated during two years with autologous dendritic cells loaded by messenger RNA electroporation with the Wilms' tumor antigen (WT1). The dendritic cell therapy product will be generated and generally administered in the coordinating center, which is the Antwerp University Hospital, more specifically the Center for Cell Therapy and Regenerative Medicine (CCRG) and the Division of Hematology, both headed by Prof. Zwi Berneman. After inclusion of 130 efficacy-evaluable patients, relapse rate, relapse-free survival and overall survival analysis will be performed. Tumor marker levels and immune activation will also be monitored to compare the 2 groups at a molecular and immunological level. General and disease-specific quality of life will be evaluated using quality of life questionnaires at regular time points.

Being tested
DC vaccine
Keywords
in complete remission, Adult (>18 years) at very high risk of relapse
Medical subject headings
Leukemia, Myeloid, Acute, Pathologic Complete Response

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DC vaccineBiological

    Autologous WT1 mRNA-electroporated DCs

Study groups in NCT01686334
Study groupRoleWhat they receive
DC vaccineExperimentalVaccination with autologous WT1 mRNA-electroporated DCs plus follow-up care. Patients receiving low-intensity chemotherapy are allowed to continue this treatment in combination with DC vaccination.
Receives: Biological: DC vaccine
Control armNo interventionFollow-up care. Patients receiving low-intensity chemotherapy are allowed to continue this treatment during the follow-up care

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall survival

    The primary objective of this randomized phase II clinical study is to determine the effect of WT1-targeted dendritic cell vaccination on overall survival in adult AML patients at very high risk of relapse and in complete remission.

    Measured: At study completion, an average of 5 year

Secondary outcomes (5)

  1. Relapse rate

    to determine the effect of WT1-targeted dendritic cell vaccination on relapse rate in adult AML patients at very high risk of relapse and in complete remission.

    Measured: At study completion, an average of 5 year

  2. relapse-free survival

    to determine the effect of WT1-targeted dendritic cell vaccination on relapse-free survival in adult AML patients at very high risk of relapse and in complete remission.

    Measured: At study completion, an average of 5 year

  3. Change in WT1 mRNA levels in peripheral blood

    Efficacy assessment will also be performed on a molecular level. To this end, peripheral blood samples will be obtained from participants in both study groups (vaccine group and control group) and analyzed by qRT-PCR for WT1 expression, which is a promising molecular biomarker in AML.

    Measured: Through study completion, at every vaccination during 2 years

  4. Immune activation

    This study aims to examine the presence of leukemia-specific immune responses in AML patients in remission and to investigate whether they can be induced or increased in these patients by WT1 mRNA-electroporated DC vaccination.

    Measured: After the 4th DC vaccine

  5. General and disease-specific quality of life

    Patients will be asked to fill out general and disease-specific quality of life questionnaires to assess changes in general and disease-specific quality of life during the study at regular time points

    Measured: At study completion, an average of 5 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Sep 2012 (estimated)
  2. Study startOct 2012
  3. Primary completionDec 2025 (estimated)
  4. Study completionDec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
130 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01686334
Sponsor's protocol ID
CCRG12-001
Acronym
WIDEA
Status last verified
Mar 2024
First submitted
26 Jul 2012
Last updated
12 Mar 2024
Results posted
No

Publications

  • Van Tendeloo VF, Van de Velde A, Van Driessche A, Cools N, Anguille S, Ladell K, Gostick E, Vermeulen K, Pieters K, Nijs G, Stein B, Smits EL, Schroyens WA, Gadisseur AP, Vrelust I, Jorens PG, Goossens H, de Vries IJ, Price DA, Oji Y, Oka Y, Sugiyama H, Berneman ZN. Induction of complete and molecular remissions in acute myeloid leukemia by Wilms' tumor 1 antigen-targeted dendritic cell vaccination. Proc Natl Acad Sci U S A. 2010 Aug 3;107(31):13824-9. doi: 10.1073/pnas.1008051107. Epub 2010 Jul 14.

    PubMed 20631300

  • Van Driessche A, Van de Velde AL, Nijs G, Braeckman T, Stein B, De Vries JM, Berneman ZN, Van Tendeloo VF. Clinical-grade manufacturing of autologous mature mRNA-electroporated dendritic cells and safety testing in acute myeloid leukemia patients in a phase I dose-escalation clinical trial. Cytotherapy. 2009;11(5):653-68. doi: 10.1080/14653240902960411.

    PubMed 19530029

  • Van Driessche A, Gao L, Stauss HJ, Ponsaerts P, Van Bockstaele DR, Berneman ZN, Van Tendeloo VF. Antigen-specific cellular immunotherapy of leukemia. Leukemia. 2005 Nov;19(11):1863-71. doi: 10.1038/sj.leu.2403930.

    PubMed 16121214

  • Van Driessche A, Berneman ZN, Van Tendeloo VF. Active specific immunotherapy targeting the Wilms' tumor protein 1 (WT1) for patients with hematological malignancies and solid tumors: lessons from early clinical trials. Oncologist. 2012;17(2):250-9. doi: 10.1634/theoncologist.2011-0240. Epub 2012 Jan 30.

    PubMed 22291091

  • Anguille S, Willemen Y, Lion E, Smits EL, Berneman ZN. Dendritic cell vaccination in acute myeloid leukemia. Cytotherapy. 2012 Jul;14(6):647-56. doi: 10.3109/14653249.2012.693744.

    PubMed 22686130

  • Anguille S, Lion E, Smits E, Berneman ZN, van Tendeloo VF. Dendritic cell vaccine therapy for acute myeloid leukemia: questions and answers. Hum Vaccin. 2011 May;7(5):579-84. doi: 10.4161/hv.7.5.14652. Epub 2011 May 1.

    PubMed 21422813

  • Smits EL, Anguille S, Cools N, Berneman ZN, Van Tendeloo VF. Dendritic cell-based cancer gene therapy. Hum Gene Ther. 2009 Oct;20(10):1106-18. doi: 10.1089/hum.2009.145.

    PubMed 19656053

  • Anguille S, Van de Velde AL, Smits EL, Van Tendeloo VF, Juliusson G, Cools N, Nijs G, Stein B, Lion E, Van Driessche A, Vandenbosch I, Verlinden A, Gadisseur AP, Schroyens WA, Muylle L, Vermeulen K, Maes MB, Deiteren K, Malfait R, Gostick E, Lammens M, Couttenye MM, Jorens P, Goossens H, Price DA, Ladell K, Oka Y, Fujiki F, Oji Y, Sugiyama H, Berneman ZN. Dendritic cell vaccination as postremission treatment to prevent or delay relapse in acute myeloid leukemia. Blood. 2017 Oct 12;130(15):1713-1721. doi: 10.1182/blood-2017-04-780155. Epub 2017 Aug 22.

    PubMed 28830889

  • Van Acker HH, Versteven M, Lichtenegger FS, Roex G, Campillo-Davo D, Lion E, Subklewe M, Van Tendeloo VF, Berneman ZN, Anguille S. Dendritic Cell-Based Immunotherapy of Acute Myeloid Leukemia. J Clin Med. 2019 Apr 27;8(5):579. doi: 10.3390/jcm8050579.

    PubMed 31035598

  • Smits EL, Stein B, Nijs G, Lion E, Van Tendeloo VF, Willemen Y, Anguille S, Berneman ZN. Generation and Cryopreservation of Clinical Grade Wilms' Tumor 1 mRNA-Loaded Dendritic Cell Vaccines for Cancer Immunotherapy. Methods Mol Biol. 2016;1393:27-35. doi: 10.1007/978-1-4939-3338-9_3.

    PubMed 27033213

  • Z. Berneman, S. Anguille, Y. Willemen, A. Van de Velde, P. Germonpré, M. Huizing, V. Van Tendeloo, K. Saevels, L. Rutsaert, K. Vermeulen, A. Snoeckx, B. Op de Beeck, N. Cools, G. Nijs, B. Stein, E. Lion, A. van Driessche, M. Peeters, E. Smits. Vaccination of cancer patients with dendritic cells electroporated with mRNA encoding the Wilms' Tumor protein (WT1): correlation of clinical effect and overall survival with T-cell response. Cytotherapy 2019, 21(5), p. S10.

  • Z. Berneman, A. Van de Velde, S. Anguille, Y. Willemen, M. Huizing, P. Germonpré, K. Saevels, G. Nijs, N. Cools, A. Van Driessche, B. Stein, H. De Reu, W. Schroyens, A. Gadisseur, A. Verlinden, K. Vermeulen, M. Maes, M. Lammens, H. Goossens, M. Peeters, V. Van Tendeloo, E. Smits. Vaccination with Wilms' Tumor Antigen (WT1) mRNA-Electroporated Dendritic Cells as an Adjuvant Treatment in 60 Cancer Patients: Report of Clinical Effects and Increased Survival in Acute Myeloid Leukemia, Metastatic Breast Cancer, Glioblastoma and Mesothelioma. Cytotherapy 2016, 18(6), p. S13-14

  • Shallis RM, Podoltsev NA. Maintenance therapy for acute myeloid leukemia: sustaining the pursuit for sustained remission. Curr Opin Hematol. 2021 Mar 1;28(2):110-121. doi: 10.1097/MOH.0000000000000637.

    PubMed 33394722

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing DC vaccine in people with Acute Myeloid Leukemia, run by Zwi Berneman at 8 sites in Belgium.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 12 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall survival (time frame: At study completion, an average of 5 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01686334, which also lists 13 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Mar 2024.

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