Therapeutic vaccination with dendritic cells loaded with wilms' tumor 1 protein in patients with myeloid malignancies and multiple myeloma MedDRA version: 12.0 Level: LLT Classification code 10046859 Term: Vaccination MedDRA version: 12.0 Level: LLT Classification code 10024329 Term: Leukemia MedDRA version: 12.0 Level: LLT Classification code 10028228 Term: Multiple myeloma
Conditions
Interventions
Product Name: dendritic cells
Product Code: DC
Pharmaceutical Form: Suspension for injection
Sponsors
Antwerp University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Tumor type: • Acute Myeloid Leukemia (AML) according to the WHO criteria (ea at least 20% blasts in the marrow). This % should be assessed on a BM aspiration or, in case of dry tap, on a BM biopsy. All FAB subtypes except M3. (Patients with Myelodysplastic Syndrome, category of Refractory Anemia with Excess Blasts (RAEB): RAEB I (WHO: medullary blast count = 10% and a peripheral blast count = 5%) and RAEB II (WHO: medullary blast count > 10% and/or > 5% peripheral blasts) can be included in the study in absence of other non-experimental treatment modalities.) • Chronic myeloid leukemia (CML): patients in chronic phase under therapy with tyrosinase kinase inhibitors who have sub-optimal response or failure according to the European Leukemianet guidelines (Baccarani et al. Blood 2006) and who are not eligible for hematopoietic stem cell transplantation • Multiple Myeloma (MM): symptomatic with active disease: o Presence of serum/urine M protein (> 3 g/dl) o Bone marrow plasmacytosis (>10-30%) o Anemia, renal failure, hypercalcemia, and/or lytic bone lesions 2. Extent of disease: a. AML: i. clinical remission after at least one course of polychemotherapy ii. high risk of relapse defined as (and/or): 1. Age > 60 years (if =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Subjects with concurrent additional malignancy (with exception of non-melanoma skin cancers and carcinoma in situ of the cervix) 2. Subjects who are pregnant 3. Subjects who have sensitivity to drugs that provide local anesthesia 4. Subjects needing corticosteroids 1 mg/kg during vaccination; corticosteroids are allowed as part of their treatment when taken = 30 days before the start of vaccination.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to evaluate the immunogenicity and clinical efficacy of intradermal vaccination with autologous RNA-modified dendritic cells (DCs) – engineered to express the WT1 protein – in patients with myeloid malignancies, i.e. acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) and multiple myeloma (MM). ;Secondary Objective: The secondary objective of this study is to evaluate if the level of WT1 RNA in the peripheral blood, next to being a biomarker for monitoring (minimal) residual disease in AML, could also serve as an informative marker to evaluate the effect of a WT1-targeted cancer vaccine and to monitor minimal residual disease in AML, CML and MM.;Primary end point(s): Immunogenicity of intradermal DC vaccination (cellular + humoral immunity against WT1 antigen) as measured by: 1.In vivo cytokine response (serum concentration of cytokines) 2.In vivo anti-WT1 antibody responses 3.In vitro T cell reactivity towards MHC class I and II-restricted WT1 epitopes by multiplex-cytokine assay using peripheral blood and DTH-infiltrating T cells. For more details on the immune-monitoring analysis, see section 7. 4.Delayed type hypersensitivity (DTH) responses to intradermally injected DC alone; DC + sig-WT1-DClamp mRNA + KLH (= vaccine); DC+ sig-WT1-DClamp mRNA; KLH (positive control) and PBS (negative control) 5.Quantitative and qualitative FACS analysis of WT1-specific-positive CD8+ T cells using HLA-A2 WT1 multimers (only for HLA-A2+ patients). | — |
Countries
Belgium
Outcome results
None listed