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

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ClinicalTrials.gov Identifier: NCT01686334
Recruitment Status : Recruiting
First Posted : September 18, 2012
Last Update Posted : February 6, 2018
Sponsor:
Collaborators:
Kom Op Tegen Kanker
stichting tegen kanker
Research Foundation - Flanders (FWO: Fonds Wetenschappelijk Onderzoek)
Information provided by (Responsible Party):
Zwi Berneman, University Hospital, Antwerp

Brief 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) patients by eradicating minimal residual disease.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Biological: DC vaccine Phase 2

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 138 patients with acute myeloid leukemia (AML). Adult patients (> 18 years) with AML who have entered morphological CR or CRi after (1) at least one course of induction and one course of consolidation chemotherapy or (2) at least two cycles to maximum six cycles of hypomethylating agents; 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 hypomethylating agents 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 8 years or until 138 efficacy-evaluable AML patients are included. In the interventional group, 69 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 138 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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 138 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : October 2012
Estimated Primary Completion Date : July 2024


Arm Intervention/treatment
Experimental: DC vaccine
Vaccination with autologous WT1 mRNA-electroporated DCs plus follow-up care. Patients receiving hypomethylating agents are allowed to continue this treatment in combination with DC vaccination.
Biological: DC vaccine
Autologous WT1 mRNA-electroporated DCs

No Intervention: Control arm
Follow-up care. Patients receiving hypomethylating agents are allowed to continue this treatment during the follow-up care



Primary Outcome Measures :
  1. Relapse rate [ Time Frame: At study completion, an average of 5 year ]
    The primary objective of this randomized phase II clinical study is 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.

  2. Disease-free survival [ Time Frame: At study completion, an average of 5 year ]
    The primary objective of this randomized phase II clinical study is to determine the effect of WT1-targeted dendritic cell vaccination on disease-free survival in adult AML patients at very high risk of relapse and in complete remission.

  3. Overall survival [ Time Frame: At study completion, an average of 5 year ]
    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.


Secondary Outcome Measures :
  1. Change in WT1 mRNA levels in peripheral blood [ Time Frame: Through study completion, at every vaccination during 2 years ]
    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.

  2. Immune activation [ Time Frame: After the 4th DC vaccine ]
    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.

  3. General and disease-specific quality of life [ Time Frame: At study completion, an average of 5 year ]
    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


Other Outcome Measures:
  1. Tertiary: Safety [ Time Frame: At study completion, an average of 5 year ]
    To corroborate the safety of WT1 mRNA-electroporated DC vaccination in adult patients with AML. Safety will be assessed at every visit by adverse event reporting and clinical laboratory tests.

  2. Exploratory: Effect of hypomethylating agents (HMA) [ Time Frame: At study completion, an average of 5 year ]
    To evaluate the effect of HMA on the primary and secondary objectives.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).
  • Completion of (1) at least one cycle of induction chemotherapy and one cycle of consolidation chemotherapy OR (2) at least two cycles to maximum six cycles of hypomethylating agents 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

o 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 chemotherapy administration (in case of HMA: last HMA 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 HMA: 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01686334


Contacts
Contact: Zwi N Berneman, MD, PhD +32 3 8213780 zwi.berneman@uza.be
Contact: Ann Van de Velde, MD, PhD +32 3 8213916 ann.vandevelde@uza.be

Locations
Belgium
ZNA Stuivenberg Recruiting
Antwerp, Belgium, 2060
Contact: Local Investigator: Dimitri Breems, MD, PhD         
Antwerp University Hospital Recruiting
Antwerp, Belgium, 2650
Principal Investigator: Zwi N Berneman, MD, PhD         
University Hospital Brussels Recruiting
Brussels, Belgium, 1090
Contact: Local Investigator: Rik Schots, MD, PhD         
Cliniques Universitaires Saint-Luc Recruiting
Brussel, Belgium, 1200
Contact: Local Investigator: Violaine Havelange , MD, PhD         
Ghent University Hospital Recruiting
Ghent, Belgium, 9000
Contact: Local Investigator: Tessa Kerre , MD, PhD         
Centre Hospitalier Universitaire de Liège Recruiting
Liège, Belgium, 4000
Contact: Local Investigator: Yves Beguin , MD, PhD         
AZ Delta Recruiting
Roeselare, Belgium, 8800
Contact: Local Investigator: Dries Deeren , MD         
CHU Mont Godinne Recruiting
Yvoir, Belgium, 5530
Contact: Local Investigator: Carlos Graux , MD, PhD         
Sponsors and Collaborators
Zwi Berneman
Kom Op Tegen Kanker
stichting tegen kanker
Research Foundation - Flanders (FWO: Fonds Wetenschappelijk Onderzoek)
Investigators
Principal Investigator: Zwi Berneman, MD, PhD University Hospital, Antwerp
Principal Investigator: Evelien LJ Smits, MSc, PhD Universiteit Antwerpen
Principal Investigator: Sébastien Anguille, MD, PhD University Hospital, Antwerp
Principal Investigator: Ann Van de Velde, MD, PhD University Hospital, Antwerp

Publications:

Responsible Party: Zwi Berneman, Full Professor, University Hospital, Antwerp
ClinicalTrials.gov Identifier: NCT01686334     History of Changes
Other Study ID Numbers: CCRG12-001
First Posted: September 18, 2012    Key Record Dates
Last Update Posted: February 6, 2018
Last Verified: February 2018

Keywords provided by Zwi Berneman, University Hospital, Antwerp:
in complete remission
Adult (>18 years) at very high risk of relapse

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Vaccines
Immunologic Factors
Physiological Effects of Drugs