Clinical Trials /

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

NCT01686334

Description:

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.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Efficacy Study of Dendritic Cell Vaccination in Patients With Acute Myeloid Leukemia in Remission
  • 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

Clinical Trial IDs

  • ORG STUDY ID: CCRG12-001
  • NCT ID: NCT01686334

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
DC vaccineDC vaccine

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 acute myeloid leukemia (AML) patients by eradicating minimal residual disease.

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.
    

Trial Arms

NameTypeDescriptionInterventions
DC vaccineExperimentalVaccination 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.
    Control armNo InterventionFollow-up care. Patients receiving hypomethylating agents are allowed to continue this treatment during the follow-up care

      Eligibility 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
            
      Maximum Eligible Age:N/A
      Minimum Eligible Age:18 Years
      Eligible Gender:All
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Relapse rate
      Time Frame:At study completion, an average of 5 year
      Safety Issue:
      Description: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.

      Secondary Outcome Measures

      Measure:Change in WT1 mRNA levels in peripheral blood
      Time Frame:Through study completion, at every vaccination during 2 years
      Safety Issue:
      Description: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.
      Measure:Immune activation
      Time Frame:After the 4th DC vaccine
      Safety Issue:
      Description: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.
      Measure:General and disease-specific quality of life
      Time Frame:At study completion, an average of 5 year
      Safety Issue:
      Description: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

      Details

      Phase:Phase 2
      Primary Purpose:Interventional
      Overall Status:Recruiting
      Lead Sponsor:Zwi Berneman

      Trial Keywords

      • in complete remission
      • Adult (>18 years) at very high risk of relapse

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