Efficacy Study of Dendritic Cell Vaccination in Patients With Acute Myeloid Leukemia in Remission
Conditions
Acute Myeloid Leukemia
Conditions: official terms
Leukemia - Leukemia, Myeloid - Leukemia, Myeloid, Acute
Conditions: Keywords
in complete remission, older then 65 years
Study Type
Interventional
Study Phase
Phase 2
Study Design
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: DC vaccine
Type: Biological
Overall Status
Recruiting
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 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). 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.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 65 Years
Gender: Both
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.
Location
Antwerp University Hospital
Antwerp, Belgium
Status: Recruiting
Start Date
October 2012
Sponsors
Zwi Berneman
Source
University Hospital, Antwerp
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page