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.
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
Interventions
Drug | Synonyms | Arms |
---|
DC vaccine | | DC 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 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.
Trial Arms
Name | Type | Description | Interventions |
---|
DC vaccine | Experimental | Vaccination 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. | |
Control arm | No Intervention | Follow-up care. Patients receiving low-intensity chemotherapy 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) unless treated with
CPX-351 chemotherapy or hypomethylating agents combined with venetoclax.
- 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.
- Interval between the completion of the last intensive chemotherapy administration (in
case of low-intensity chemotherapy: last 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
low-intensity chemotherapy: 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: | Overall survival |
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 overall survival in adult AML patients at very high risk of relapse and in complete remission. |
Secondary Outcome Measures
Measure: | Relapse rate |
Time Frame: | At study completion, an average of 5 year |
Safety Issue: | |
Description: | 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. |
Measure: | relapse-free survival |
Time Frame: | At study completion, an average of 5 year |
Safety Issue: | |
Description: | 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. |
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
Last Updated
January 19, 2021