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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by University Hospital, Antwerp
Sponsor:
Information provided by (Responsible Party):
Zwi Berneman, University Hospital, Antwerp
ClinicalTrials.gov Identifier:
NCT01686334
First received: July 26, 2012
Last updated: July 3, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Acute Myeloid Leukemia
Biological: DC vaccine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Wilms' Tumor (WT1) Antigen-targeted Dendritic Cell Vaccination to Prevent Relapse in Patients Older Than 65 Years With Acute Myeloid Leukemia: a Multicenter Randomized Phase II Trial

Resource links provided by NLM:


Further study details as provided by University Hospital, Antwerp:

Primary Outcome Measures:
  • Relapse rate [ Designated as safety issue: No ]
    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 AML patients older than 65 years and in complete remission.

  • Disease-free survival [ Designated as safety issue: No ]
    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 AML patients older than 65 years and in complete remission.

  • Overall survival [ Designated as safety issue: No ]
    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 AML patients older than 65 years and in complete remission.


Secondary Outcome Measures:
  • Change in WT1 mRNA levels in peripheral blood [ Designated as safety issue: No ]
    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.

  • Immune activation [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 138
Study Start Date: October 2012
Estimated Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: DC vaccine
Vaccination with autologous WT1 mRNA-electroporated DCs plus follow-up care
Biological: DC vaccine
Autologous WT1 mRNA-electroporated DCs
No Intervention: Control arm
Follow-up care

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). Patients older than 65 years who are in complete hematological remission will be randomized to be vaccinated with dendritic cells or to receive regular 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 2012 and will last for three 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.

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of acute myeloid leukemia (AML) according to the 2008 criteria of the World Health Organization (WHO).18

    • 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).
  • WT1 transcript levels in peripheral blood and/or bone marrow increased above background at the time of diagnosis, as determined by qRT-PCR.
  • Completion of at least one cycle of induction chemotherapy and one cycle of consolidation chemotherapy 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 and the start of vaccination (or the start of follow-up in case of the control arm): 6 weeks (minimum) and 16 weeks (maximum).
  • Age: >65 years at the time of enrollment.
  • WHO performance status: grade 0 or 1 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01686334

Contacts
Contact: Zwi N Berneman, MD, PhD +32 3 8213780 zwi.berneman@uza.be
Contact: Sébastien Anguille, MD +32 3 8215696 sebastien.anguille@uza.be

Locations
Belgium
Antwerp University Hospital Recruiting
Antwerp, Belgium, 2650
Principal Investigator: Zwi N Berneman, MD, PhD         
Sponsors and Collaborators
Zwi Berneman
Investigators
Principal Investigator: Zwi Berneman, MD, PhD University Hospital, Antwerp
Principal Investigator: Evelien LJ Smits, PhD Universiteit Antwerpen
Principal Investigator: Sébastien Anguille, MD University Hospital, Antwerp
  More Information

Publications:

Responsible Party: Zwi Berneman, Full Professor, University Hospital, Antwerp
ClinicalTrials.gov Identifier: NCT01686334     History of Changes
Other Study ID Numbers: CCRG12-001
Study First Received: July 26, 2012
Last Updated: July 3, 2014
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products

Keywords provided by University Hospital, Antwerp:
in complete remission
older then 65 years

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on October 29, 2014